MF研究者総覧

研究者データベース

詳細
小川　浩司(オガワ　コウジ)
北海道大学病院　内科
助教
researchmap個人ページ
Last Updated :2023/11/29

基本情報

所属

  • 北海道大学病院　内科

職名

  • 助教

学位

  • 博士（医学）（北海道大学）

科研費研究者番号

  • 20735188

J-Global ID

研究分野

  • ライフサイエンス / 消化器内科学

担当教育組織

所属学協会

  • 日本超音波医学会   日本消化器内視鏡学会   日本肝臓学会   日本消化器病学会   日本内科学会   

研究活動情報

論文

  • Yusuke Uchinami, Naoki Miyamoto, Daisuke Abo, Ryo Morita, Koji Ogawa, Tatsuhiko Kakisaka, Ryusuke Suzuki, Tomohiko Miyazaki, Hiroshi Taguchi, Norio Katoh, Hidefumi Aoyama
    Journal of radiation research 2023年11月22日 
    The SyncTraX series enables real-time tumor-tracking radiotherapy through the real-time recognition of a fiducial marker using fluoroscopic images. In this system, the isocenter should be located within approximately 5-7.5 cm from the marker, depending on the version, owing to the limited field of view. If the marker is placed away from the tumor, the isocenter should be shifted toward the marker. This study aimed to investigate stereotactic body radiotherapy (SBRT) outcomes of primary liver tumors treated with SyncTraX in cases where the isocenter was shifted marginally or outside the planning target volume (PTV). Twelve patients with 13 liver tumors were included in the analysis. Their isocenter was shifted toward the marker and was placed marginally or outside the PTV. The prescribed doses were generally 40 Gy in four fractions or 48 Gy in eight fractions. The overall survival (OS) and local control (LC) rates were calculated using the Kaplan-Meier method. All patients completed the scheduled SBRT. The median distance between the fiducial marker and PTV centroid was 56.0 (interquartile range [IQR]: 52.7-66.7) mm. By shifting the isocenter toward the marker, the median distance between the marker and isocenter decreased to 34.0 (IQR: 33.4-39.7) mm. With a median follow-up period of 25.3 (range: 6.9-70.0) months, the 2-year OS and LC rates were 100.0% (95% confidence interval: 100-100). An isocenter shift makes SBRT with SyncTraX feasible in cases where the fiducial marker is distant from the tumor.
  • 【薬物療法によって変貌する肝細胞癌治療:2023 Update】Advanced stage肝細胞癌 Phase 3 HIMALAYA試験の結果とその解釈
    荘 拓也, 須田 剛生, 北潟谷 隆, 大原 正嗣, 中井 正人, 小川 浩司, 坂本 直哉
    肝胆膵 87 4 439 - 446 (株)アークメディア 2023年10月
  • IMbrave150基準外進行肝細胞癌に対するアテゾリズマブ+ベバシズマブ併用療法の治療効果と肝予備能変化
    荘 拓也, 須田 剛生, 大原 正嗣, 中井 正人, 小川 浩司, 出水 孝章, 目黒 高志, 中村 晃久, 高木 智史, 馬場 英, 古家 乾, 鈴木 和治, 山本 義也, 伊藤 淳, 山田 錬, 宮城島 拓人, 坂本 直哉
    肝胆膵 87 4 508 - 509 (株)アークメディア 2023年10月
  • 小川 浩司, 大原 正嗣, 坂本 直哉
    日本臨床 81 増刊7 ウイルス性肝炎学2023 203 - 208 (株)日本臨床社 2023年07月
  • Masato Nakai, Kenichi Morikawa, Takashi Sasaki, Risako Kohya, Sonoe Yoshida, Shunichi Hosoda, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Masatsugu Ohara, Takuya Sho, Goki Suda, Koji Ogawa, Naoya Sakamoto
    Journal of gastroenterology 58 7 656 - 667 2023年07月 
    BACKGROUND: Acute kidney injury (AKI) is associated with liver cirrhosis (LC), water retention, diuretics to treat water retention, and a poor prognosis. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) reportedly predicts a poor prognosis in decompensated LC. This study investigated the usefulness of uNGAL in predicting the short- and long-term effects of tolvaptan (TVP) and the incidence of AKI post-TVP administration. METHODS: Of the LC cases with water retention, 86 with available pre-treatment uNGAL were analyzed. A short-term response was defined as weight loss of ≥ 1.5 kg within the first week; a long-term response was defined as a short-term response without early recurrence. The uNGAL usefulness in predicting the short- and long-term effects of TVP and AKI incidence post-TVP administration was investigated. RESULTS: Short-term effects of TVP were observed in 52 patients. Of these, 15 patients had an early recurrence. In multivariate analysis, significant short-term predictive factors were C-reactive protein (CRP) < 1.4 mg/dl, uNa/K ratio ≥ 3.51, and uNGAL < 50.2 ng/ml. Patients were classified according to these three cut-off values, with short-term response rates of 92.9%, 68.8%, 26.7%, and 0% for 0, 1, 2, and 3 points, respectively. CRP < 0.94 mg/dl and uNGAL < 50.2 ng/ml were significant factors for predicting the long-term response of TVP. The AKI incidence post-TVP was 8.1% (n = 7) and was significantly higher among those with uNGAL ≥ 38.1 ng/mL. CONCLUSION: uNGAL is a useful predictor of the short- and long-term efficacy of TVP and can be useful in predicting AKI incidence post-TVP administration.
  • Risako Kohya, Goki Suda, Masatsugu Ohara, Takashi Sasaki, Tomoka Yoda, Naofumi Sakurai, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Osamu Maehara, Shunsuke Ohnishi, Yoshimasa Tokuchi, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
    Cancers 15 12 2023年06月20日 
    Lenvatinib, used for unresectable hepatocellular carcinoma (HCC), causes appetite loss, but the underlying mechanisms, clinical impact, and predictive factors have been unclear. The endocrine factor FGF21 modulates appetite and is involved in cachexia. We evaluated the association between FGF21 level changes during lenvatinib treatment for unresectable HCC and appetite loss. Sixty-three eligible unresectable HCC patients who started lenvatinib treatment between 2018 and 2021 were included. We analyzed FGF21 levels at baseline; 1, 2, and 4 weeks after lenvatinib initiation, and before the onset of appetite loss. Grade ≥ 2 lenvatinib-induced appetite loss led to liver functional reserve deterioration at disease progression and a poor prognosis. Baseline characteristics and serum FGF21 levels were similar between patients with and without appetite loss. However, the serum FGF21 change rate increased significantly at 4 weeks post-lenvatinib initiation in patients with grade ≥ 2 appetite loss, as compared to those without appetite loss. Similar significant increases in the serum FGF21 level change rate were observed prior to grade ≥ 2 appetite loss onset. This suggests that changes in FGF21 levels can be used to predict patients with a greater risk of marked appetite loss and provides insights into the mechanisms underlying lenvatinib-induced appetite loss in patients with HCC.
  • Takashi Sasaki, Goki Suda, Masatsugu Ohara, Shunichi Hosoda, Naoki Kawagishi, Risako Kohya, Tomoka Yoda, Osamu Maehara, Shunsuke Ohnishi, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Yoshimasa Tokuchi, Takashi Kitagataya, Kazuharu Suzuki, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Sho Komukai, Koji Ogawa, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 2023年06月18日 
    AIM: Although hepatitis delta virus (HDV) coinfection with hepatitis B virus (HBV) is a global health concern, the global prevalence of HDV infections remains unknown due to insufficient data in many countries. In Japan, HDV prevalence has not been updated for over 20 years. We aimed to investigate the recent prevalence of HDV infections in Japan. METHODS: We screened 1264 consecutive patients with HBV infection at Hokkaido University Hospital between 2006 and 2022. Patients' serums were preserved and subsequently tested for HDV antibody (immunoglobulin-G). Available clinical information was collected and analyzed. We compared the changes in liver fibrosis using the Fibrosis-4 (FIB-4) index between propensity-matched patients with and without the evidence of anti-HDV antibodies and corrected for baseline FIB-4 index, nucleoside/nucleotide analog treatment, alcohol intake, sex, HIV coinfection, liver cirrhosis, and age. RESULTS: After excluding patients without properly stored serums and those lacking appropriate clinical information, 601 patients with HBV were included. Of these, 1.7% of patients had detectable anti-HDV antibodies. Patients with anti-HDV antibody serum positivity had a significantly higher prevalence of liver cirrhosis, significantly lower prothrombin time, and a higher prevalence of HIV coinfection than those who demonstrated serum anti-HDV antibody negativity. A propensity-matched longitudinal analysis revealed that liver fibrosis (FIB-4 index) progressed more rapidly in patients with positive results for anti-HDV antibody tests. CONCLUSIONS: The recent prevalence of HDV infections in Japanese patients with HBV was 1.7% (10/601). These patients experienced rapid liver fibrosis progression, highlighting the importance of routine HDV testing.
  • 大原 正嗣, 小川 浩司, 長谷川 智子, 新明 康弘, 坂本 直哉, 是永 匡紹
    肝臓 64 6 289 - 291 (一社)日本肝臓学会 2023年06月 
    当院肝疾患相談センターでは、院内非専門診療科での肝炎ウイルス陽性者(陽性者)の肝臓専門医(消化器内科)への紹介対策として、電子カルテアラートシステムによる陽性者対応を行っているが、アラートが通知された後に、必ずしも肝臓専門医への紹介や問診に至らず、未対応のままの患者が存在していることが判明した。そこで、院内非専門診療科で陽性者数が最も多かった眼科の外来看護師3名を肝炎医療コーディネーター(肝Co)として新たに養成・配置し、令和2年から要対応者には肝Coが個別対応を行っている。今回、肝Co配置前後(平成31年～令和3年)の眼科における陽性者数(B型肝炎ウイルス、C型肝炎ウイルス合算)、紹介率、要対応率の推移について検討、報告した。その結果、陽性者数は、39名(平成31年)、29名(令和2年)、30名(令和3年)で、紹介率は、肝Coの介入(肝Coが設置された令和2年は、平成31年まで遡って対応)により、アラート通知による平成31年の18.0%が25.6%まで改善し、以後、令和2年27.6%、令和3年26.7%と推移している。未対応者の指標となる要対応率については、アラート通知のみの28.2%(平成31年)、34.5%(令和2年)、20.0%(令和3年)が、肝Coの介入により2.6%(平成31年)、3.4%(令和2年)、6.7%(令和3年)と大幅に低下、改善した。
  • Shunichi Hosoda, Goki Suda, Takuya Sho, Koji Ogawa, Megumi Kimura, Zijian Yang, Sonoe Yoshida, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Jun Ito, Takuto Miyagishima, Naoya Sakamoto
    Liver cancer 12 2 156 - 170 2023年06月 
    INTRODUCTION: Atezolizumab plus bevacizumab treatment is highly effective in patients with unresectable hepatocellular carcinoma (HCC). However, progressive disease (PD) occurs in approximately 20% of HCC patients treated with atezolizumab plus bevacizumab, resulting in a poor prognosis. Thus, the prediction and early detection of HCC is crucial. METHODS: Patients with unresectable HCC treated with atezolizumab plus bevacizumab and had baseline preserved serum (n = 68) were screened and classified according to their PD, 6 weeks after treatment initiation (early PD; n = 13). Of these, 4 patients each with and without early PD were selected for cytokine array and genetic analyses. The identified factors were validated in the validated cohort (n = 60) and evaluated in patients treated with lenvatinib. RESULTS: No significant differences were observed in the genetic alterations in circulating tumor DNA. Cytokine array data revealed that baseline MIG (CXCL9), ENA-78, and RANTES differed substantially between patients with and without early PD. Subsequent analysis in the validation cohort revealed that baseline CXCL9 was significantly lower in patients with early PD than that in patients without early PD, and the best cut-off value of serum CXCL9 to predict early PD was 333 pg/mL (sensitivity: 0.600, specificity: 0.923, AUC = 0.75). In patients with lower serum CXCL9 (<333 pg/mL), 35.3% (12/34) experienced early PD with atezolizumab plus bevacizumab, while progression-free survival (PFS) was significantly shorter relative to that in patients without (median PFS, 126 days vs. 227 days; HR: 2.41, 95% CI: 1.22-4.80, p = 0.0084). While patients with objective response to lenvatinib had significantly lower CXCL9 levels compared with those of patients without. CONCLUSION: Baseline low serum CXCL9 (<333 pg/mL) levels may predict early PD in patients with unresectable HCC treated with atezolizumab plus bevacizumab.
  • A病院における肝炎検査陽性者拾い上げの取り組み 眼科・整形外科外来との協働
    長谷川 智子, 小川 浩司, 大原 正嗣, 櫻井 菜々子, 中野 政子, 坂本 直哉
    肝臓 64 Suppl.1 A281 - A281 (一社)日本肝臓学会 2023年04月
  • Yoshimasa Tokuchi, Goki Suda, Naoki Kawagishi, Masatsugu Ohara, Risako Kohya, Takashi Sasaki, Tomoka Yoda, Osamu Maehara, Shunsuke Ohnishi, Akinori Kubo, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Takashi Kitagataya, Kazuharu Suzuki, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 53 7 595 - 606 2023年03月21日 
    AIM: Hepatitis C virus (HCV) infection has been reported to cause liver steatosis. Thus, eradicating HCV with direct-acting antivirals (DAAs) is expected to reduce liver steatosis. We aimed to clarify long-term changes in the prevalence of fatty liver and hyper-low-density lipoprotein (LDL) cholesterolemia and their associations in patients who achieve successful HCV eradication using DAAs. METHODS: This retrospective study included patients with HCV who achieved sustained virologic response after interferon-free DAA and analyzed the changes in the prevalence of fatty liver diagnosed with controlled attenuation parameter (CAP), hyper-LDL cholesterolemia, and their relationships at baseline (n = 100) and 24 weeks (SVR24, n = 100), 96 weeks (SVR96, n = 100), and 144 weeks (SVR144, n = 90) after DAA. RESULTS: In 100 participants, the prevalence of fatty liver (19% vs. 32%, p = 0.0349) and hyper-LDL cholesterolemia (6% vs. 15%, p = 0.0379) significantly increased without changes in body weight at SVR96. Median total cholesterol, low-density lipoprotein cholesterol (LDL-C), and small-dense-LDL (sdLDL) levels and CAP values were significantly greater at SVR24, SVR96, and SVR144 than at baseline. Baseline CAP values and changes in CAP values were significantly negatively correlated at every observation point: r = -0.5305, p < 0.0001 at SVR24; r = -0.3617, p = 0.0005 at SVR96; and r = -0.4735, p < 0.0001 at SVR144. A similar relationship was observed in cholesterol levels. Unlike at baseline, CAP values were significantly positively correlated with LDL-C and sdLDL-C levels at all observation points after DAAs. CONCLUSIONS: Direct-acting antivirals may cause an increased prevalence of fatty liver accompanying hyper-LDL cholesterolemia without increased body weight. As post-SVR liver steatosis could cause HCC, careful follow-up may be required.
  • 肝細胞腺腫との鑑別が困難であった限局性結節性過形成の1例
    吉田 苑永, 小川 浩司, 佐々木 貴志, 甲谷 理紗子, 細田 峻一, 久保 彰則, 得地 祐匡, 大原 正嗣, 中井 正人, 荘 拓也, 須田 剛生, 坂本 直哉
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 132回・126回 42 - 42 日本消化器病学会-北海道支部 2023年03月
  • BCLCステージB2肝癌に対してアテゾリズマブ+ベバシズマブ併用療法と焼灼療法にてCancer Freeが得られた1症例
    細田 峻一, 荘 拓也, 佐々木 貴志, 甲谷 理紗子, 吉田 苑永, 得地 祐匡, 大原 正嗣, 中井 正人, 須田 剛生, 小川 浩司, 坂本 直哉
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 132回・126回 46 - 46 日本消化器病学会-北海道支部 2023年03月
  • 中井 正人, 小川 浩司, 佐々木 貴志, 甲谷 理紗子, 吉田 苑永, 細田 俊一, 得地 祐匡, 北潟谷 隆, 大原 正嗣, 荘 拓也, 須田 剛生, 坂本 直哉
    日本消化器病学会雑誌 120 臨増総会 A417 - A417 (一財)日本消化器病学会 2023年03月
  • Zijian Yang, Goki Suda, Osamu Maehara, Masatsugu Ohara, Tomoka Yoda, Takashi Sasaki, Risako Kohya, Sonoe Yoshida, Shunichi Hosoda, Yoshimasa Tokuchi, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
    Cancers 15 3 2023年01月18日 
    The possible mechanisms of resistance to atezolizumab/bevacizumab for unresectable HCC, and the subsequent response to these therapies, remain underexplored. The sequential changes in serum growth factors, including VEGF-A, VEGF-C, VEGF-D, ANG-2, FGF-19, HGF, and EGF during atezolizumab/bevacizumab for unresectable HCC were evaluated in 46 patients. Patients who experienced PD after CR, PR, or SD to atezolizumab/bevacizumab were evaluated. A total of 4, 9, 19, and 14 patients showed CR, PR, SD, and PD, respectively. Of 32 patients with disease control, 28 experienced PD after CR, PR, or SD with atezolizumab/bevacizumab. Baseline growth factor levels were similar between patients with or without disease control and those with or without an objective response. Growth factor changes between the baseline and the best overall response points (BOR) for patients with disease control showed that FGF-19 significantly increased and ANG2 significantly decreased at the BOR. Growth factor changes between the BOR and the PD point in 28 patients who experienced PD after disease control showed that VEGF-D and ANG2 significantly increased at the PD point compared with that at the BOR. Summarily, increased serum VEGF-D and ANG-2 levels might contribute to developing resistance to atezolizumab/bevacizumab for unresectable HCC and might be target molecules in subsequent salvage therapies.
  • Yusuke Uchinami, Norio Katoh, Daisuke Abo, Ryo Morita, Hiroshi Taguchi, Yoshihiro Fujita, Takahiro Kanehira, Ryusuke Suzuki, Naoki Miyamoto, Seishin Takao, Taeko Matsuura, Takuya Sho, Koji Ogawa, Tatsuya Orimo, Tatsuhiko Kakisaka, Keiji Kobashi, Hidefumi Aoyama
    The British journal of radiology 96 1144 20220720 - 20220720 2023年01月12日 [査読有り]
     
    OBJECTIVES: In a previous study of hepatic toxicity, the following three factors were identified to predict the benefits of proton beam therapy (PBT) for hepatocellular carcinomas (HCC) with a maximum diameter of ≤5 cm and Child-pugh grade A (CP-A): number of tumors (one vs ≥2), the location of tumors (hepatic hilum or others), and the sum of the diameters of lesions. The aim of this study is to analyze the association between these three factors and hepatic toxicity. METHODS: We retrospectively reviewed patients of CP-A treated with PBT or photon stereotactic body radiotherapy (X-ray radiotherapy, XRT) for HCC ≤5 cm. For normal liver dose, the V5, V10, V20 (volumes receiving 5, 10, and 20 Gy at least), and the mean dose was evaluated. The albumin-bilirubin (ALBI) and CP score changes from the baseline were evaluated at 3 and 6 months after treatment. RESULTS: In 89 patients (XRT: 48, PBT: 41), those with two or three (2-3) predictive factors were higher normal liver doses than with zero or one (0-1) factor. In the PBT group, the ALBI score worsened more in patients with 2-3 factors than those with 0-1 factor, at 3 months (median 0.26 vs 0.02, p = 0.032) and at 6 months (median: 0.35 vs 0.10, p = 0.009). The ALBI score change in the XRT group and CP score change in either modality were not significantly different in the number of predictive factors. CONCLUSIONS: The predictive factor numbers predicted the ALBI score change in PBT but not in XRT. ADVANCES IN KNOWLEDGE: This study suggest that the number of predictive factors previously identified (0-1 vs 2-3) were significantly associated with dosimetric parameters of the normal liver in both modalities. In the proton group, the number of predictive factors was associated with a worsening ALBI score at 3 and 6 months, but these associations were not found in the photon SBRT group.
  • Naoki Kawagishi, Goki Suda, Yoshiya Yamamoto, Masaru Baba, Ken Furuya, Osamu Maehara, Shunsuke Ohnishi, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Yoshimasa Tokuchi, Takashi Kitagataya, Masatsugu Ohara, Kazuharu Suzuki, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
    Viruses 15 1 2023年01月07日 
    Progressive liver fibrosis after anti-HCV treatment is a risk factor for HCC. Angiopoietin-2 (Ang2) is associated with non-regression of liver fibrosis after direct-acting antiviral (DAA). This study evaluated the predictive value of serum Ang2 levels for HCC occurrence or recurrence after DAA administration. In this retrospective study, 310 HCV-infected patients treated with DAAs in 2014-2020 were screened and evaluated for HCC occurrence or recurrence every three-six months. Multivariate Cox regression analysis revealed that age ≥ 75 years (HR: 2.92, 95% CI: 1.34-6.33; p = 0.007) and baseline Ang2 level ≥ 464 pg/mL (HR: 2.75, 95% CI: 1.18-6.37; p = 0.019) were significantly associated with HCC occurrence after DAA therapy. A high or low risk of HCC after DAA therapy could be distinguished by the combination of age and baseline Ang2 level. The cumulative incidences of de-novo HCC at two and four years were 0.8% and 3.8% in the low-risk group and 22.6% and 27.1% in the high-risk group, respectively. Baseline Ang2 level ≥ 402 pg/mL was significantly associated with HCC recurrence in patients who achieved sustained virological response with DAAs (HR: 3.68). In conclusion, serum Ang2 levels can predict HCC occurrence and recurrence after successful HCV eradication by DAAs.
  • Goki Suda, Masaru Baba, Yoshiya Yamamoto, Takuya Sho, Koji Ogawa, Megumi Kimura, Shunichi Hosoda, Sonoe Yoshida, Akinori Kubo, Qingjie Fu, Zijian Yang, Yoshimasa Tokuchi, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Jun Ito, Tomoe Kobayashi, Izumi Tsunematsu, Naoya Sakamoto
    Journal of medical virology 95 2 e28452  2023年01月04日 
    BACKGROUND: No prospective study on the efficacy of tenofovir alafenamide (TAF), a novel tenofovir prodrug, in preventing HBV reactivation has yet been reported. METHODS: This multicenter prospective study enrolled HBV-carriers who received TAF to prevent HBV reactivation before antitumor or immunosuppressive therapy, and patients with resolved HBV infection who experienced HBV-reactivation and received TAF to prevent HBV reactivation-related hepatitis. The efficacy of prophylactic TAF in preventing HBV reactivation and HBV reactivation-related hepatitis was evaluated at 6 and 12 months after initiating TAF. RESULTS: Overall, 110 patients were administered TAF to prevent HBV reactivation or HBV reactivation-related hepatitis. Three patients died owing to primary disease, whereas one patient was transferred to another hospital within 6 months after initiating TAF. Seven patients died due to primary disease, and five patients were transferred to another hospital within 12 months after initiating TAF. Therefore, 106 and 94 (77 patients with HBV infection, 17 with previous-HBV infection) patients were evaluated at 6 and 12 months after initiating TAF, respectively. No patient experienced HBV reactivation, HBV reactivation-related hepatitis, or treatment discontinuation due to HBV reactivation or adverse events of TAF after 6 and 12 months. CONCLUSION: TAF could effectively prevent HBV reactivation and HBV reactivation-related hepatitis. This article is protected by copyright. All rights reserved.
  • Masatsugu Ohara, Goki Suda, Risako Kohya, Takashi Sasaki, Tomoka Yoda, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Osamu Maehara, Shunsuke Ohnishi, Yoshimasa Tokuchi, Takashi Kitagataya, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
    Frontiers in nutrition 10 1272728 - 1272728 2023年 
    INTRODUCTION: We aimed to assess the prognostic implications of muscle atrophy and high subcutaneous adipose tissue (SAT) radiodensity in patients with hepatocellular carcinoma (HCC). METHODS: In this retrospective study, muscle atrophy was assessed using the psoas muscle index (PMI) obtained from computed tomography. SAT radiodensity was evaluated based on radiodensity measurements. Survival and multivariate analyses were performed to identify factors associated with prognosis. The impact of muscle atrophy and high SAT radiodensity on prognosis was determined through survival analysis. RESULTS: A total of 201 patients (median age: 71 years; 76.6% male) with HCC were included. Liver cirrhosis was observed in 72.6% of patients, and the predominant Child-Pugh grade was A (77.1%). A total of 33.3% of patients exhibited muscle atrophy based on PMI values, whereas 12.9% had high SAT radiodensity. Kaplan-Meier survival analysis demonstrated that patients with muscle atrophy had significantly poorer prognosis than those without muscle atrophy. Patients with high SAT radiodensity had a significantly worse prognosis than those without it. Muscle atrophy, high SAT radiodensity, the Barcelona Clinic Liver Cancer class B, C, or D, and Child-Pugh score ≥ 6 were significantly associated with overall survival. Further classification of patients into four groups based on the presence or absence of muscle atrophy and high SAT radiodensity revealed that patients with both muscle atrophy and high SAT radiodensity had the poorest prognosis. CONCLUSION: Muscle atrophy and high SAT radiodensity are significantly associated with poor prognosis in patients with HCC. Identifying this high-risk subgroup may facilitate the implementation of targeted interventions, including nutritional therapy and exercise, to potentially improve clinical outcomes.
  • 和久井 洋佑, 後藤 了一, 渡辺 正明, 川村 典生, 小川 浩司, 三橋 智子, 嶋村 剛, 武冨 紹信
    日本消化器病学会雑誌 119 12 1096 - 1102 (一財)日本消化器病学会 2022年12月 
    症例は15歳女性.黄疸を主訴に近医受診し,急性肝不全型Wilson病(T-bil9.2mg/dl,PT41.3%)と診断され,MELD25点で脳死待機リストへ登録した.当初緊急の肝移植が必要な状況であったが,急性期の集学的治療により待機中の状態を維持しえた.待機期間18ヵ月で脳死ドナー発生,脳死肝移植を施行した.脳死ドナーの発生が少ない本邦においては,特に長期待機可能な全身管理が重要である.(著者抄録)
  • Ren Yamada, Kenichi Morikawa, Kiyohiko Hotta, Daiki Iwami, Tatsu Tanabe, Sachiyo Murai, Nobuo Shinohara, Sonoe Yoshida, Shunichi Hosoda, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Megumi Kimura, Koji Yamamoto, Masato Nakai, Takuya Sho, Goki Suda, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
    Journal of viral hepatitis 29 11 976 - 985 2022年11月 
    Donors with resolved hepatitis B virus (HBV) infection may be a solution for the organ shortage for kidney transplantation (KT). The purpose of this study was to clarify the current state of HBV markers after KT from donors with resolved HBV infection to HBV naïve recipients and the rate of HBV reactivation in recipients with resolved HBV infection. Furthermore, we investigated HBV covalently closed circular DNA (cccDNA) in transplanted organs from donors with resolved HBV infection and the capability of HBV replication in kidney cell lines. We retrospectively analysed the HBV status of 340 consecutive donors and recipients who underwent KT in a single centre. We prospectively measured cccDNA by real-time polymerase chain reaction in kidney biopsy specimens of 32 donors with resolved HBV infection. HBV reactivation was found in three recipients with resolved HBV infection (4.8%, 3/63) after KT. We analysed 45 cases of transplantation from donors with resolved HBV infection to HBV-naive recipients. One case (2.2%, 1/45) became seropositive for hepatitis B core antibody (anti-HBc) and in another case (2.2%, 1/45), HBV-DNA was detected qualitatively in an HBV naive recipient with a donor with resolved HBV infection. In the latter case, cccDNA was measured in the donor kidney during KT. HBV replication was observed in kidney cell lines with HBV plasmid transfection. In conclusion, the risk of reactivation in anti-HBc-positive donors is relatively low. However, post-transplant HBV monitoring should be conducted in all at-risk cases.
  • Naoki Kawagishi, Goki Suda, Ryotaro Sakamori, Takeshi Matsui, Masahiro Onozawa, Zijian Yang, Sonoe Yoshida, Masatsugu Ohara, Megumi Kimura, Akinori Kubo, Osamu Maehara, Qingjie Fu, Shunichi Hosoda, Yoshimasa Tokuchi, Kazuharu Suzuki, Masato Nakai, Takuya Sho, Kenichi Morikawa, Mitsuteru Natsuizaka, Koji Ogawa, Hajime Sakai, Shunsuke Ohnishi, Masaru Baba, Tetsuo Takehara, Naoya Sakamoto
    Scientific reports 12 1 16800 - 16800 2022年10月07日 
    De novo hepatitis B virus (HBV) reactivation occurs during direct-acting antiviral (DAA) treatment in hepatitis C virus (HCV)-infected patients with resolved HBV infection. We evaluated the predictive factors, mechanical insight, and differences of cytokine levels during anti-cancer/immunosuppressive and DAA. Eleven, 35, and 19 HCV-infected patients with previous HBV infection with HBV reactivation during DAA treatment, previous HBV infection without HBV reactivation during DAA treatment, and without HBV infection resolution receiving DAA treatment, respectively, were enrolled. Clinical data and baseline cytokine levels were analyzed. Low baseline serum interleukin (IL)-1β levels predicted de novo HBV reactivation during DAA treatment (odds ratio: 47.6, 95% confidence interval: 6.94-333.3). HCV-infected patients with the IL-1β gene single nucleotide polymorphism rs16944 AA allele had significantly higher IL-1β levels; no HCV-infected patient with the IL-1β AA allele experienced HBV reactivation during DAA treatment. Compared to HCV-infected patients with HBV infection resolution, non-HCV infected patients with or without HBV reactivation during anti-cancer/immunosuppressive therapy or bone marrow transplantation had remarkably lower baseline IL-1β levels. Low IL-1β levels were not associated with HBV reactivation. IL-1β levels before DAA for HCV-infected patients with resolved HBV infection could predict HBV reactivation during DAA treatment.
  • Kazutaka Terahara, Tian-Cheng Li, Keiji Matsubayashi, Hidekatsu Sakata, Takanobu Kato, Atsushi Naganuma, Koji Ogawa, Koichi Honda, Jun Itakura, Noriyuki Akutsu, Hiroshi Tobita, Masaaki Korenaga, Tatsuya Kanto, Ryuichi Sugiyama, Ryosuke Suzuki, Isao Hamaguchi, Masanori Isogawa, Yoshimasa Takahashi
    Microbiology spectrum 10 5 e0214622  2022年09月20日 
    This study aimed to calibrate hepatitis E virus (HEV) serological assays. We optimized the previously developed in-house HEV antibody enzyme-linked immunosorbent assay (ELISA) by setting the cutoff with an in-house serological performance panel consisting of broad HEV antibody titers and subtracting nonspecific background values for anti-HEV IgM, IgA, and IgG. We also compared the assay's performance with that of commercial serological assay kits (four kits for IgM, one for IgA, and two for IgG). Although all serological assays readily detected HEV antibodies at high titers in the symptomatic hepatitis E population, considerable variations between assays were observed in the asymptomatic population. The in-house ELISA showed a higher sensitivity for HEV IgM, IgA, and IgG than the commercial kits and detected the seroconversion of HEV IgM and IgG earlier when testing a commercially available HEV seroconversion panel. The low sensitivity of the commercial kits was due to the high setting of the original cutoff, which was demonstrated by receiver operating characteristic analysis. However, the corrected cutoff value reduced assay specificity. Background subtraction is essential to achieve high specificity because the in-house ELISA without background subtraction reduced its specificity. These results indicate that asymptomatic specimens and background subtraction contribute to the optimization of HEV serological assays. IMPORTANCE Accurate diagnosis of hepatitis E virus (HEV) infection is essential for public health surveillance and for preventing HEV-contaminated blood transfusion. Anti-HEV IgM or IgA is used as a reliable marker of recent HEV infection. However, considerable variability in the sensitivity and specificity of HEV antibody detection is observed among several commercially available assay kits. In addition, none of the HEV antibody detection methods have been approved by the U.S. Food and Drug Administration (FDA). Here, we show that the in-house enzyme-linked immunosorbent assay (ELISA) could detect HEV IgM and IgA more sensitively than commercial kits in the asymptomatic population. We also suggest that the assay performance of commercial kits might be improved by optimizing the cutoff and reducing nonspecific background noise. A sensitive serological (IgM or IgA) assay in addition to HEV RNA testing will contribute to accurate diagnosis of acute HEV infection because HEV RNA-positive duration is relatively short.
  • 【進化する肝細胞癌の薬物療法:2022 update】免疫療法の基礎と臨床 免疫療法(単剤・複合療法)の効果は肝細胞癌のetiologyと関係するか
    小川 浩司, 大原 正嗣, 中井 正人, 荘 拓也, 須田 剛生, 坂本 直哉
    肝胆膵 85 3 393 - 398 (株)アークメディア 2022年09月
  • 切除不能進行肝細胞癌に対するアテゾリズマブ+ベバシズマブ併用療法の治療効果と肝予備能変化
    荘 拓也, 出水 孝章, 目黒 高志, 中村 晃久, 上林 実, 高木 智史, 馬場 英, 古家 乾, 鈴木 和治, 山本 義也, 伊藤 淳, 山田 錬, 宮城島 拓人, 須田 剛生, 大原 正嗣, 中井 正人, 小川 浩司, 坂本 直哉
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 131回・125回 39 - 39 日本消化器病学会-北海道支部 2022年09月
  • 肝血管筋脂肪腫の1切除例
    佐々木 貴志, 甲谷 理紗子, 細田 峻一, 吉田 苑永, 得地 祐匡, 久保 彰則, 大原 正嗣, 須田 剛生, 中井 正人, 荘 拓也, 小川 浩司, 坂本 直哉, 相山 健, 武冨 紹信, 岡崎 ななせ, 松野 吉宏
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 131回・125回 40 - 40 日本消化器病学会-北海道支部 2022年09月
  • 肝硬変体液貯留に対するトルバプタン投与症例における尿NGAL測定の有用性
    中井 正人, 森川 賢一, 吉田 苑永, 細田 峻一, 久保 彰則, 得地 祐匡, 北潟谷 隆, 山田 錬, 大原 正嗣, 荘 拓也, 須田 剛生, 小川 浩司, 坂本 直哉
    肝臓 63 Suppl.2 A592 - A592 (一社)日本肝臓学会 2022年09月
  • Takuya Sho, Goki Suda, Yoshiya Yamamoto, Ken Furuya, Masaru Baba, Koji Ogawa, Akinori Kubo, Yoshimasa Tokuchi, Qingjie Fu, Zijian Yang, Megumi Kimura, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Tomofumi Takagi, Jun Ito, Tomoe Kobayashi, Takuto Miyagishima, Naoya Sakamoto
    Cancers 14 16 2022年08月15日 
    The IMbrave150 trial demonstrated the high efficacy and safety of atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC). In this multicenter study, the efficacy of this combination and its effect on liver functional reserve were evaluated in patients not meeting the eligibility criteria of IMbrave150. Of 115 patients with unresectable HCC treated with atezolizumab and bevacizumab between October 2020 and January 2022, 72 did not meet the eligibility criteria of IMbrave150, most frequently due to a history of systemic therapy (60/72), platelet counts < 75 × 109/L (7/72), Child-Pugh B (9/72), and 2+ proteinuria (8/72). Atezolizumab and bevacizumab therapy was equally effective for patients who did or did not meet the eligibility criteria (PFS, 6.5 vs. 6.9 months, p = 0.765), consistent with subgroup analyses of histories of systemic therapy, platelet counts, Child-Pugh, and proteinuria. Baseline ALBI scores were worse in patients who did not meet the criteria than in those who did and significantly worsened after treatment initiation in patients not meeting the criteria (baseline vs. 12 weeks; 2.35 ± 0.43 vs. -2.18 ± 0.54; p = 0.007). Accordingly, atezolizumab plus bevacizumab was effective for patients not meeting the eligibility criteria of IMbrave150, although careful monitoring for changes in liver functional reserve is needed.
  • Masato Nakai, Kenichi Morikawa, Shunichi Hosoda, Sonoe Yoshida, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Masatsugu Ohara, Takuya Sho, Goki Suda, Koji Ogawa, Naoya Sakamoto
    World journal of hepatology 14 7 1480 - 1494 2022年07月27日 
    BACKGROUND: The Mac-2 binding protein glycosylation isomer (M2BPGi), a fibrosis marker in various liver diseases, is reportedly a prognostic marker in patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. AIM: To evaluate whether the M2BPGi value, M2BP, and pre-sarcopenia before radiofrequency ablation (RFA) could be useful recurrence and prognostic markers in patients with early-stage HCC. METHODS: In total, 160 patients with early-stage primary HCC treated with RFA were separately analyzed as hepatitis C virus (HCV)-positive and HCV-negative. Factors contributing to recurrence and liver-related death, including M2BP, M2BPGi, and skeletal muscle mass index, were statistically analyzed. Eighty-three patients were HCV-positive and 77 were HCV-negative. RESULTS: In HCV-positive patients, only des-γ-carboxy-prothrombin ≥ 23 mAU/mL was a significant poor prognostic factor affecting survival after RFA. In HCV-negative patients, M2BPGi ≥ 1.86 cutoff index was significantly associated with tumor recurrence, while M2BP was not. M2BPGi ≥ 1.86 cutoff index (hazard ratio, 4.89; 95% confidence interval: 1.97-12.18; P < 0.001) and pre-sarcopenia (hazard ratio, 3.34, 95% confidence interval: 1.19-9.37; P = 0.022) were independent significant poor prognostic factors in HCV-negative patients. CONCLUSION: In HCV-negative patients with primary HCC treated with RFA, lower M2BPGi contributed to a lower tumor recurrence rate and longer survival period. Pre-sarcopenia contributed to the poor prognosis independently in HCV-negative patients. These factors might be useful recurrence and prognostic markers for early-stage primary HCC.
  • Akihisa Nakamura, Koji Yamamoto, Rei Takeda, Ren Yamada, Akinori Kubo, Kenichi Morikawa, Sayaka Ando, Tomoe Shimazaki, Takaaki Izumi, Machiko Umemura, Takashi Kitagataya, Taku Shigesawa, Kazuharu Suzuki, Megumi Kimura, Masato Nakai, Takuya Sho, Goki Suda, Mitsuteru Natsuizaka, Koji Ogawa, Shunsuke Ohnishi, Toshiro Sugiyama, Hiroshi Takeda, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 52 6 508 - 521 2022年06月 
    BACKGROUND AND AIMS: Although various noninvasive markers and prediction formulas for nonalcoholic steatohepatitis (NASH) have been reported, they are of value only in the diagnosis of the advanced fibrosis stage of NASH. In this study, we evaluated soluble CD14 (sCD14) as a diagnostic marker for discriminating NASH from nonalcoholic fatty liver disease (NAFLD) using an animal model and clinical specimens. METHODS: Serum sCD14 levels were measured in samples derived from mice with diet-induced NASH and patients using an enzyme-linked immunosorbent assay. Our cohort enrolled 126 patients with liver needle biopsy-proven NAFLD. RESULTS: The intestinal defense mechanism in NASH model mice was altered as a consequence of the unique gut environment. Elevated serum levels of sCD14 were observed in mice with diet-induced NASH, and the condition of the liver was exacerbated as a result of exposure to gut-derived endotoxin. We confirmed that the serum sCD14 levels in NAFL patients significantly differed from those in NASH patients. The area under the curve for distinguishing between NAFL and NASH was 0.891. Moreover, we found that serum sCD14 levels were weakly correlated with the inflammation grade based on the NAFLD activity score (NAS), the grade of fibrosis according to the Brunt fibrosis classification, and a positive correlation with the grade of ballooning based on NAS in patients with NAFLD. CONCLUSION: sCD14 could be a useful pathophysiological marker and diagnostic adjunct distinguishing NASH from NAFLD. The use of sCD14 may allow the screening and identification of high-risk groups for NASH development and support early therapeutic interventions.
  • 非アルコール性脂肪肝炎、非代償性肝硬変のhigh MELD例に実施した脳死肝移植の一例
    中村 恒星, 後藤 了一, 巖築 慶一, 川村 典生, 渡辺 正明, 森川 賢一, 小川 浩司, 坂本 直哉, 嶋村 剛, 武冨 紹信
    日本外科学会定期学術集会抄録集 122回 RS - 2 (一社)日本外科学会 2022年04月
  • Sonoe Yoshida, Goki Suda, Masatsugu Ohara, Megumi Kimura, Zijian Yang, Osamu Maehara, Qingjie Fu, Shunichi Hosoda, Kubo Akinori, Yoshimasa Tokuchi, Ren Yamada, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 52 7 603 - 613 2022年03月30日 
    AIM: A high prevalence of overestimated renal function in patients with liver cirrhosis (LC) has been reported; nonetheless, its impact on prognosis remains unclear. We aimed to evaluate the impact of overestimated renal function on prognosis in patients with LC. METHODS: An overestimated renal function was defined as a >20% increase in the creatinine-based estimated glomerular filtration rate (eGFR), compared with cystatin C-based eGFR. LC patients with conserved serum, who were evaluated for muscle atrophy and had proper clinical information were included, and their prognostic factors were analyzed. RESULTS: A total of 215 consecutive patients with LC were included. The prevalence of overestimated renal function was 29.8% (64/215). Kaplan-Meier survival analysis revealed that patients with overestimated renal function had a poorer prognosis than those without overestimated renal function (hazard ratio [HR]: 2.217 95% confidence interval [CI]: 1.290-3.810; P=0.001). Subgroup analysis showed that overestimated renal function was a significant prognostic factor, irrespective of sex and the presence of hepatocellular carcinoma (HCC). Multivariate Cox regression analyses revealed that overestimated renal function was a significant and independent factor predictive of poor prognosis in the entire cohort (HR: 2.050; 95% CI: 1.041-4.037; P=0.038) and in subgroups classified by Child-Pugh class A (HR: 2.131; 95% CI: 1.019-4.458; P=0.044), Model for End-Stage Liver Disease score <9 (HR: 2.303; 95% CI: 1.038-5.109; P=0.04), and presence of HCC (HR: 2.290; 95% CI: 1.128-4.651; P=0.022). CONCLUSION: Overestimated renal function is a significant and independent prognostic factor in patients with LC. This article is protected by copyright. All rights reserved.
  • Machiko Umemura, Koji Ogawa, Kenichi Morikawa, Akinori Kubo, Yoshimasa Tokuchi, Ren Yamada, Takashi Kitagataya, Taku Shigesawa, Tomoe Shimazaki, Megumi Kimura, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Naoki Kawagishi, Takaaki Izumi, Masato Nakai, Takuya Sho, Goki Suda, Mitsuteru Natsuizaka, Kota Ono, Kazumoto Murata, Masaya Sugiyama, Masashi Mizokami, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 52 7 586 - 596 2022年03月29日 
    BACKGROUND & AIMS: Benefits of nucleos(t)ide analogs (NAs) on hepatitis B surface antigen (HBsAg) reduction and interferon-lambda3 (IFN-λ3) induction are still not known. This study aimed to investigate the effects of NAs on HBsAg reduction and association with serum IFN-λ3 levels in chronic hepatitis B (CHB) patients. METHODS: A total of 91 patients [51 treated with nucleoside analog entecavir hydrate (ETV) and 40 treated with nucleotide analog adefovir dipivoxil (ADV) or tenofovir disoproxil fumarate (TDF)] with clinically evident CHB (chronic hepatitis, 57; liver cirrhosis, 34) were enrolled in this study. Serum IFN-λ3 levels among patients receiving ETV and ADV/TDF were measured before the initiation of therapy and 1, 3, and 5 years post-therapy. RESULTS: The change (mean ± standard deviation) in serum HBsAg levels from baseline to year five was -0.38 ± 0.46 and -0.84 ± 0.64 log10 IU/ml in ETV and ADV/TDF groups, respectively (p = 0.0004). Higher serum IFN-λ3 levels were observed in ADV/TDF group compared with ETV group during treatment (p < 0.001). Serum IFN-λ3 levels showed negative correlation with HBsAg reduction in ADV/TDF group (r = -0.386, p = 0.038) at week 48. Nucleotide analogs (ADV/TDF) treatment has associated factors with -0.3 log HBsAg decline at 1 year, -0.5 log HBsAg decline at 3 years, and -0.8 log HBsAg decline at 5 years after NAs treatment on multivariate analysis. CONCLUSIONS: Nucleotide analog (ADV/TDF) treatment reduced HBsAg levels greater compared with nucleoside analog (ETV) in parallel with IFN-λ3 induction.
  • 再活性化が疑われた急性E型肝炎の1例
    久保 彰則, 小川 浩司, 吉田 苑永, 細田 峻一, 得地 祐匡, 山田 錬, 北潟谷 隆, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 石田 勢津子, 坂本 直哉
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 130回・124回 55 - 55 日本消化器病学会-北海道支部 2022年03月
  • 若年女性に見られた肝細胞腺腫症の1例
    北潟谷 隆, 吉田 苑永, 細田 俊一, 久保 彰則, 得地 祐匡, 山田 錬, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉, 高桑 恵美, 中島 収
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 130回・124回 56 - 56 日本消化器病学会-北海道支部 2022年03月
  • 肝癌に対する新世代マイクロ波凝固療法の治療成績
    中井 正人, 吉田 苑永, 細田 峻一, 久保 彰則, 得地 祐匡, 北潟谷 隆, 山田 錬, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 130回・124回 70 - 70 日本消化器病学会-北海道支部 2022年03月
  • Masato Nakai, Yoshiya Yamamoto, Masaru Baba, Goki Suda, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Ken Furuya, Naoya Sakamoto
    Scientific reports 12 1 1449 - 1449 2022年01月27日 
    Liver stiffness measurement (LSM) is a useful tool for assessing advanced liver fibrosis, an important risk factor for hepatocellular carcinoma (HCC) following hepatitis C (HCV) eradication. This study aimed to clarify the non-invasive factors associated with HCC following sustained virological response (SVR) and to identify the low-risk group. 567 patients without history of HCC who achieved SVR at 24 weeks (SVR24) after IFN-free treatment were retrospectively analyzed. The cumulative incidence of HCC and the risk factors were examined using pre-treatment and SVR24 data. The median observation period was 50.2 months. Thirty cases of HCC were observed, and the 4-year cumulative incidence of HCC was 5.9%. In multivariate analysis, significant pre-treatment factors were age ≥ 71 years (hazard ratio [HR]: 3.402) and LSM ≥ 9.2 kPa (HR: 6.328); SVR24 factors were age ≥ 71 years (HR: 2.689) and LSM ≥ 8.4 kPa (HR: 6.642). In cases with age < 71 years and LSM < 8.4 kPa at the time of SVR24, the 4-year cumulative incidence of HCC was as low as 1.1%. Both pre-treatment LSM (≥ 9.2 kPa) and SVR24 LSM (≥ 8.4 kPa) and age (≥ 71 years) are useful in predicting the risk of HCC after SVR with IFN-free treatment. Identification of low-risk individuals may improve the efficiency of follow-up.
  • Zijian Yang, Goki Suda, Osamu Maehara, Masatsugu Ohara, Sonoe Yoshida, Shunichi Hosoda, Megumi Kimura, Akinori Kubo, Yoshimasa Tokuchi, Qingjie Fu, Ren Yamada, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
    Cancers 14 1 2022年01月04日 
    Serum growth factor changes and their effect on prognosis during lenvatinib for unresectable hepatocellular carcinoma (HCC) remain underexplored. The sequential changes in serum growth factors during lenvatinib for unresectable HCC were evaluated in 58 patients using complete clinical data, and preserved serum was used to investigate changes in FGF-19, ANG-2, HGF, VEGF, and EGF. Patients with a complete response (CR), partial response (PR), and stable disease (SD) were evaluated for growth factor changes between the best response and progressive disease (PD) points, classified based on these changes, and evaluated by post progression survival (PPS). A total of 8, 24, 18, and 8 patients showed CR, PR, SD, and PD, respectively. Multivariate analysis revealed that age, relative dose intensity, and baseline ANG-2 were significantly associated with treatment response. Growth factor changes between the best response and PD points revealed that patients could be classified into four groups based on the EGF, ANG-2, and HGF changes. Although patient characteristics at baseline and PD, their response to lenvatinib, and PFS were similar among those groups, patients with an increase in all growth factors had significantly shorter PPS (median PPS was 553, 323, and 316 versus 173 days in groups 1-4 p = 0.032). We revealed that the evaluation of the changes in growth factors during lenvatinib could predict PPS.
  • Yosuke Wakui, Ryoichi Goto, Masaaki Watanabe, Norio Kawamura, Koji Ogawa, Tomoko Mitsuhashi, Tsuyoshi Shimamura, Akinobu Taketomi
    Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 119 12 1096 - 1102 2022年 
    A 15-year-old female patient was diagnosed with a fulminant-type Wilson's disease. She had severe illness with a Model for End-Stage Liver Disease score of 25 and new Wilson Index score of 11. She underwent plasma exchanges, hemodiafiltration, and administration of fresh frozen plasma on consecutive days. Finally, she had recovered from severe illness and was discharged from the hospital. After 18 months of waiting time, she underwent deceased liver transplantation and returned to normal daily life. In Japan, the critical shortage of donated organs requires a long waiting time. Previous studies demonstrated that artificial liver support systems, including plasma exchange and hemodiafiltration, could be useful for a fulminant-type Wilson's disease. For such a disease, multidisciplinary bridging treatments are crucial for a successful liver transplantation.
  • Michiko Takimoto-Sato, Toshinari Miyauchi, Masaru Suzuki, Hideyuki Ujiie, Toshifumi Nomura, Tomoo Ikari, Tomohiko Nakamura, Kei Takahashi, Machiko Matsumoto-Sasaki, Hirokazu Kimura, Hiroki Kimura, Yuichiro Matsui, Takashi Kitagataya, Ren Yamada, Kazuharu Suzuki, Akihisa Nakamura, Masato Nakai, Takuya Sho, Koji Ogawa, Naoya Sakamoto, Naoko Yamaguchi, Noriyuki Otsuka, Utano Tomaru, Satoshi Konno
    Frontiers in genetics 13 870192 - 870192 2022年 
    Background: Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is an extremely rare disease caused by mutations in FAM111B, and only approximately 30 cases have been reported worldwide. Some patients develop interstitial pneumonia, which may lead to progressive pulmonary fibrosis and poor prognosis. However, no effective treatment for interstitial pneumonia associated with POIKTMP has been reported. Here, we report an autopsy case of POIKTMP, wherein interstitial pneumonia was improved by corticosteroids. Case Presentation: A 44-year-old Japanese man was referred to our hospital due to poikiloderma, hypotrichosis, and interstitial pneumonia. He developed progressive poikiloderma and muscle weakness since infancy. He also had tendon contractures, short stature, liver cirrhosis, and interstitial pneumonia. Mutation analysis of FAM111B revealed a novel and de novo heterozygous missense mutation, c.1886T > G (p(Phe629Cys)), through which we were able to diagnose the patient with POIKTMP. 3 years after the POIKTMP diagnosis, interstitial pneumonia had worsened. After 2 weeks of administrating 40 mg/day of prednisolone, his symptoms and lung shadows improved. However, he subsequently developed severe hepatic encephalopathy and eventually died of respiratory failure due to bacterial pneumonia and pulmonary edema. Autopsy revealed an unclassifiable pattern of interstitial pneumonia, as well as the presence of fibrosis and fatty degeneration in several organs, including the liver, kidney, skeletal muscle, heart, pancreas, and thyroid. Conclusions: We report a case of POIKTMP in which interstitial pneumonia was improved by corticosteroids, suggesting that corticosteroids could be an option for the treatment of interstitial pneumonia associated with this disease.
  • Masato Nakai, Goki Suda, Koji Ogawa, Sonoe Yoshida, Shunichi Hosoda, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Taku Shigesawa, Masatsugu Ohara, Takuya Sho, Kenichi Morikawa, Naoya Sakamoto
    PloS one 17 7 e0270786  2022年 
    Covert hepatic encephalopathy (CHE) impairs patient quality of life and occurs in approximately 30% of liver cirrhosis (LC) cases. Japanese clinical practice guidelines recommend rifaximin to treat overt HE (OHE). However, the usefulness of rifaximin against CHE is not thoroughly investigated in Japanese patients. We aimed to investigate the efficacy of rifaximin against hyperammonemia and CHE in Japan. We observed 102 patients with HE showing hyperammonemia secondary to LC and examined various biochemical and behavioral parameters following rifaximin treatment. CHE was diagnosed when the patients exhibited two or more abnormal neuropsychological test (NPT) scores but did not indicate OHE symptoms. In the 102 cases, a significant therapeutic effect of rifaximin on hyperammonemia was observed from 2 to 48 weeks after starting treatment. Excluding 10 patients diagnosed with OHE upon starting rifaximin treatment, 12 of the 92 remaining patients (11.8%) transitioned to OHE within 1 year. The 1 year cumulative OHE transition rate was 14.5%. Among the 24 patients with CHE diagnosed by the NPT for whom NPT results could be evaluated at 4 and 12 weeks after starting treatment, 10 (41.6%) had recovered from CHE at 12 weeks. When the factors contributing to recovery from CHE were examined by multivariate analysis, an ammonia level <129 μg/dL was a significant factor. Rifaximin was thus significantly effective against both hyperammonemia and CHE in Japanese patients.
  • Kazuharu Suzuki, Goki Suda, Yoshiya Yamamoto, Satoshi Abiko, Kenji Kinoshita, Shuichi Miyamoto, Ryo Sugiura, Megumi Kimura, Osamu Maehara, Ren Yamada, Takashi Kitagataya, Taku Shigesawa, Masatsugu Ohara, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    PloS one 17 1 e0261760  2022年 
    For long-term treatment of hepatitis B virus (HBV) infection, switching from tenofovir-disoproxil-fumarate (TDF) to tenofovir-alafenamide (TAF) may prevent renal dysfunction and bone loss. However, the precise effects of this switch on the blood lipid profile remain to be clarified. This is an important issue as TDF is known to have effects on both low- and high-density lipids. Therefore, our retrospective multi-center study aimed to evaluate the effects of switching from TDF to TAF on the lipid profile of patients with HBV infection. Samples were obtained prior to the switch from TDF to TAF and at 6-12 months after TAF initiation. In some cases, additional samples obtained pre- and post-TDF administration were available for analysis. Serum cholesterol levels, including oxidized-low-density lipoprotein (LDL) and non-high-density lipoprotein-cholesterol (HDL-c), and the rate of dyslipidemia, according to the NCEP-ATP III lipid risk classification, were analyzed. The data from 69 patients were analyzed, including 33 patients with pre- and post-TDF-initiation serum samples. Total cholesterol (T-chol), HDL-c, LDL-c, non-HDL-c, and oxidized LDL levels increased significantly after switching to TAF. With regard to sequential changes pre- to post-TAF, TDF was associated with significantly lower serum T-chol, HDL-c, and oxidized LDL-c levels, with T-chol, HDL-c, LDL-c, and oxidized LDL-c levels increasing significantly after the switch. The switch from TDF to TAF was also associated with an increase in the rate of dyslipidemia, from 33% to 39%, with an increase in the rate of severe dyslipidemia of 1.4% and 5.8%, based on T-chol and LDL-c levels. Of note, no cases of severe dyslipidemia were detected pre-TAF treatment. As oxidized LDL-c and non-HDL-c are strongly associated with atherosclerosis development, careful monitoring of lipid is needed after switching from TDF to TAF in this clinical population.
  • Takuya Sho, Kenichi Morikawa, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Taku Shigesawa, Mugumi Kimura, Masato Nakai, Goki Suda, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
    World journal of gastrointestinal oncology 13 12 2076 - 2087 2021年12月15日 
    The phase III clinical trial of the novel molecular targeted agent (MTA) lenvatinib for patients with advanced hepatocellular carcinoma (HCC) (REFLECT trial) found that lenvatinib was non-inferior to sorafenib in overall survival. Recently, the efficacy of multiple MTAs, including lenvatinib, in practice has been reported, and therapeutic strategies for Barcelona Clinic Liver Cancer (BCLC) intermediate stage HCC are undergoing major changes. Based on these results, lenvatinib could be recommended for patients with transcatheter arterial chemoembolization (TACE)-refractory, ALBI grade 1, within the up-to-seven criteria in the BCLC intermediate stage. Lenvatinib provides a more favorable outcome than TACE, even in cases with large or multinodular HCC beyond the up-to-seven criteria with Child-Pugh grade A. When patients meet the definitions of TACE-refractory or TACE-unsuitable, switching to systemic chemotherapy, including lenvatinib, is for favorable for preserving liver function. If initial treatment, including MTA, has a significant therapeutic effect and downstaging of HCC is obtained, additional TACE or surgical resection should be considered. Lenvatinib also has a therapeutic effect for poorly differentiated type and non-simple nodular type HCC thanks to the survival-prolonging effect of this drug. Furthermore, a significant therapeutic effect is expected in tumors with more than 50% liver involvement or main portal vein invasion, which have traditionally been considered to have a poor prognosis in patients. This suggests that at the start of lenvatinib treatment, HCC patients with ALBI grade 1 may be able to maintain liver functional reserve.
  • 小川 浩司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
    臨床消化器内科 36 13 1690 - 1694 日本メディカルセンター 2021年11月20日
  • Masato Yoshikawa, Kohsuke Kudo, Taisuke Harada, Kazutaka Harashima, Jun Suzuki, Koji Ogawa, Taro Fujiwara, Mutsumi Nishida, Ryota Sato, Toru Shirai, Yoshitaka Bito
    Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine 2021年09月04日 [査読有り]
     
    PURPOSE: The staging of liver fibrosis is clinically important, and a less invasive method is preferred. Quantitative susceptibility mapping (QSM) has shown a great potential in estimating liver fibrosis in addition to R2* relaxometry. However, few studies have compared QSM analysis and liver fibrosis. We aimed to evaluate the feasibility of estimating liver fibrosis by using QSM and R2*-based histogram analyses by comparing it with ultrasound-based transient elastography and the stage of histologic fibrosis. METHODS: Fourteen patients with liver disease were enrolled. Data sets of multi-echo gradient echo sequence with breath-holding were acquired on a 3-Tesla scanner. QSM and R2* were reconstructed by water-fat separation method, and ROIs were analyzed for these images. Quantitative parameters with histogram features (mean, variance, skewness, kurtosis, and 1st, 10th, 50th, 90th, and 99th percentiles) were extracted. These data were compared with the elasticity measured by ultrasound transient elastography and histological stage of liver fibrosis (F0 to F4, based on the new Inuyama classification) determined by biopsy or hepatectomy. The correlation of histogram parameters with intrahepatic elasticity and histologically confirmed fibrosis stage was examined. Texture parameters were compared between subgroups divided according to fibrosis stage. Receiver operating characteristic (ROC) analysis was also performed. P < 0.05 indicated statistical significance. RESULTS: The six histogram parameters of both QSM and R2*were significantly correlated with intrahepatic elasticity. In particular, three parameters (variance, percentiles [90th and 99th]) of QSM showed high correlation (r = 0.818-0.844), whereas R2* parameters showed a moderate correlation with elasticity. Four parameters of QSM were significantly correlated with fibrosis stage (ρ = 0.637-0.723) and differentiated F2-4 from F0-1 fibrosis and F3-4 from F0-2 fibrosis with areas under the ROC curve of > 0.8, but those of R2* did not. CONCLUSION: QSM may serve as a promising surrogate indicator in detecting liver fibrosis.
  • 当院における切除不能肝細胞癌に対するAtezolizumab+Bevacizumab併用療法の使用経験
    吉田 苑永, 荘 拓也, 久保 彰則, 得地 祐匡, 細田 峻一, 北潟谷 隆, 山田 錬, 中井 正人, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 129回・123回 40 - 40 日本消化器病学会-北海道支部 2021年09月
  • Lenvatinib加療後にCRに至りconversion surgeryを施行した肝内多発転移を伴う肝細胞癌の1例
    細田 峻一, 中井 正人, 吉田 苑永, 久保 彰則, 得地 祐匡, 北潟谷 隆, 山田 錬, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉, 岡崎 ななせ, 大塚 拓也, 三橋 智子
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 129回・123回 42 - 42 日本消化器病学会-北海道支部 2021年09月
  • Transient elastographyによるLSMと年齢を用いたSVR後肝発癌低リスク群の囲い込み
    中井 正人, 山本 義也, 馬場 英, 久保 彰則, 得地 祐匡, 北潟谷 隆, 山田 錬, 重沢 拓, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 古家 乾, 坂本 直哉
    肝臓 62 Suppl.2 A543 - A543 (一社)日本肝臓学会 2021年09月
  • 除不能進行肝細胞癌に対するアテゾリズマブ+ベバシズマブ併用療法の初期治療経験:多施設共同研究
    荘 拓也, 須田 剛生, 久保 彰則, 北潟谷 隆, 山田 錬, 重沢 拓, 中井 正人, 森川 賢一, 小川 浩司, 坂本 直哉
    肝臓 62 Suppl.2 A550 - A550 (一社)日本肝臓学会 2021年09月
  • 肝細胞癌において血清中表皮型脂肪酸結合タンパク質は組織中発現レベルとは独立した予後不良因子である
    大平 将史, 横尾 英樹, 小川 浩司, 深井 原, 神山 俊哉, 坂本 直哉, 武冨 紹信
    日本癌学会総会記事 80回 [J14 - 4] 2021年09月
  • Takuya Sho, Goki Suda, Koji Ogawa, Megumi Kimura, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Taku Shigesawa, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Jun Ito, Takuto Miyagishima, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 51 9 979 - 989 2021年09月 [査読有り]
     
    AIM: A clinical trial (IMbrave150) indicated the efficacy and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma (HCC). In this study, we evaluated this therapeutic combination in a real-world setting, with a focus on patients who did not meet the IMbrave150 eligibility criteria. METHODS: In this multicenter study, patients with unresectable HCC treated with atezolizumab plus bevacizumab between October 2020 and May 2021 were screened. In patients who did not meet IMbrave150 eligibility criteria, treatment responses and safety at 6 and 12 weeks were evaluated. RESULTS: Atezolizumab plus bevacizumab was initiated in 64 patients, including 46 patients (71.9%) who did not meet IMbrave150 eligibility criteria. Most of these patients had a history of systemic therapy (44/46). The objective response rate and disease control rate observed using Response Evaluation Criteria in Solid Tumors 1.1 were 5.2% and 82.8% at 6 weeks and 10.0% and 84.0% at 12 weeks, respectively; these rates were similar between patients who met and did not meet the IMbrave150 criteria. Ten patients experienced progressive disease (PD) at 6 weeks. Portal vein tumor thrombosis was significantly associated with PD (p = 0.039); none of the 15 patients with hepatitis B virus-related HCC experienced PD (p = 0.050). The most common adverse events of grade 3 or higher were aspartate aminotransferase elevation (n = 8, 13.8%) and the safety profile was similar between patients who met and did not meet the IMbrave150 criteria. CONCLUSION: Most patients treated with atezolizumab plus bevacizumab did not meet the IMbrave150 criteria; however, the combination therapy showed good safety and efficacy at the early treatment phase.
  • Yoshimasa Tokuchi, Goki Suda, Megumi Kimura, Osamu Maehara, Takashi Kitagataya, Akinori Kubo, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Masatsugu Ohara, Ren Yamada, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
    Scientific reports 11 1 16616 - 16616 2021年08月16日 [査読有り]
     
    We aimed to evaluate factors associated with changes in skeletal muscle mass in hepatitis C virus (HCV)-infected patients after treatment with direct-acting antivirals (DAAs). Consecutive HCV-infected patients after treatment with DAA were recruited into the study. Patients who achieved sustained virological response (SVR); and had complete clinical information, preserved serum samples at baseline and SVR48, and skeletal muscle mass evaluations based on the psoas muscle mass index (PMI) on computed tomography at baseline and ≥ 12 months were included. Altogether, 70.7% of patients (41/58) showed increased PMI after DAA therapy, and mean relative PMI was significantly higher after DAA therapy than at baseline. There were no significant associations between baseline clinical factors routinely examined in clinical practice and increased PMI. Among factors reported to be associated with skeletal muscle loss in patients with chronic liver disease, serum zinc levels and total and free carnitine levels increased significantly after DAA therapy and only changes in serum free carnitine levels were significantly associated with an increased PMI (r = 0305, P = 0.020). In conclusion, increased skeletal muscle mass after successful HCV eradication by DAAs was significantly associated with increased serum-free carnitine levels. L-carnitine supplementation may be beneficial in patients with low skeletal muscle mass after DAA.
  • Yusuke Uchinami, Norio Katoh, Daisuke Abo, Hiroshi Taguchi, Koichi Yasuda, Kentaro Nishioka, Takeshi Soyama, Ryo Morita, Naoki Miyamoto, Ryusuke Suzuki, Takuya Sho, Masato Nakai, Koji Ogawa, Tatsuhiko Kakisaka, Tatsuya Orimo, Toshiya Kamiyama, Shinichi Shimizu, Hidefumi Aoyama
    Hepatology research : the official journal of the Japan Society of Hepatology 51 8 870 - 879 2021年08月 [査読有り]
     
    AIM: To report the outcomes of stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinoma patients. METHODS: From January 2005 to July 2018, 63 patients with 74 lesions with a maximum diameter ≤52 mm were treated by stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system. No patient with a Child-Pugh Score ≥9 was included, and 85.6% had a score of 5 or 6. Using the biological effective dose (BED) with an α/β ratio of 10 (BED10 ), the median dose in BED10 at the reference point was 76.8 Gy (range 60-122.5 Gy). Overall survival (OS) and local control rates were assessed using the Kaplan-Meier method. RESULTS: With a median follow-up period of 24.6 months (range 0.9-118.4 months), the 1-year and 2-year OS rates were 86.8% (95% confidence interval [95% CI] 75.8-93.3) and 71.1% (57.8-81.6), respectively. The 2-year OS was 89.6% in patients with the baseline modified albumin-bilirubin (mALBI) grade =1, and 61.7% in patients with grade ≥2a. In the multivariate analysis, the mALBI grade (=1 vs. ≥2a) was a significant factor for OS (p = 0.028, 95% CI 1.11-6.18). The 1-year and 2-year local control rates were 100% (100-100%) and 92.0% (77.5-97.5%). The local control rates were significantly higher in the BED10 ≥100 Gy group than in the BED10 <100 Gy group (2-year 100% vs. 86.5%, p = 0.049) at the reference point. CONCLUSION: This retrospective study of stereotactic body radiotherapy using real-time tumor-tracking radiotherapy for hepatocellular carcinoma showed favorable outcomes with lower incidence of toxicities, especially in patients treated with BED10 ≥100 Gy to the reference point.
  • Akinori Kubo, Goki Suda, Megumi Kimura, Osamu Maehara, Yoshimasa Tokuchi, Takashi Kitagataya, Masatsugu Ohara, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
    Cancers 13 14 2021年07月20日 [査読有り]
     
    In hepatocellular carcinoma (HCC), CTNNB-1 mutations, which cause resistance to immune checkpoint inhibitors, are associated with HCC with iso-high intensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) in resectable HCC; however, analyses on unresectable HCC are lacking. This study analyzed the prevalence, characteristics, response to lenvatinib, and CTNNB-1 mutation frequency in unresectable HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI. In 52 patients with unresectable HCC treated with lenvatinib, the prevalence of iso-high intensity in the hepatobiliary phase of EOB-MRI was 13%. All patients had multiple HCCs, and 3 patients had multiple HCCs with iso-high intensity in the hepatobiliary phase of EOB-MRI. Lenvatinib response to progression-free survival and overall survival were similar between patients with or without iso-high intensity in the hepatobiliary phase of EOB-MRI. Seven patients (three and four patients who had unresectable HCC with or without iso-high intensity in the hepatobiliary phase of EOB-MRI, respectively) underwent genetic analyses. Among these, two (67%, 2/3) who had HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI carried a CTNNB-1 mutation, while all four patients who had HCC without iso-high intensity in the hepatobiliary phase of EOB-MRI did not carry the CTNNB-1 mutation. This study's findings have clinical implications for the detection and treatment of HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI.
  • Sonoe Yoshida, Goki Suda, Masatsugu Ohara, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Megumi Kimura, Kubo Akinori, Yoshimasa Tokuchi, Ren Yamada, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Osamu Maehara, Shunsuke Ohnishi, Naoya Sakamoto
    Nutrients 13 7 2021年07月14日 [査読有り]
     
    Renal dysfunction and sarcopenia are important prognostic factors in patients with chronic liver disease (CLD). Muscle atrophy can cause the overestimation of renal function based on serum creatinine. However, the frequency of overestimated renal function in Japanese patients with CLD and its relationship with sarcopenia are unclear. In present study, we evaluated the frequency of overestimated renal function, defined as a >20% higher eGFR using creatinine than using cystatin C, in 307 patients with CLD as well as its relationship with indicators of sarcopenia. In total, 24.8% of patients had overestimated renal function. In a multivariate regression analysis, liver cirrhosis (p = 0.004) and psoas muscle mass index (p = 0.049) were significantly associated with overestimated renal function. Loss of skeletal muscle mass was significantly more frequent in both male and female patients with overestimated renal function than without. In males, the loss of muscle strength and rate of sarcopenia, defined as loss of muscle mass and strength, were significantly higher in patients with than without overestimated renal function. The high frequency of overestimated renal function in Japanese patients suggests that indicators of renal function should be carefully considered; furthermore, monitoring and interventions for both renal function and sarcopenia are needed in patients with CLD.
  • Hitoshi Yoshiji, Sumiko Nagoshi, Takemi Akahane, Yoshinari Asaoka, Yoshiyuki Ueno, Koji Ogawa, Takumi Kawaguchi, Masayuki Kurosaki, Isao Sakaida, Masahito Shimizu, Makiko Taniai, Shuji Terai, Hiroki Nishikawa, Yoichi Hiasa, Hisashi Hidaka, Hiroto Miwa, Kazuaki Chayama, Nobuyuki Enomoto, Tooru Shimosegawa, Tetsuo Takehara, Kazuhiko Koike
    Hepatology research : the official journal of the Japan Society of Hepatology 51 7 725 - 749 2021年07月 
    The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japanese Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
  • Hitoshi Yoshiji, Sumiko Nagoshi, Takemi Akahane, Yoshinari Asaoka, Yoshiyuki Ueno, Koji Ogawa, Takumi Kawaguchi, Masayuki Kurosaki, Isao Sakaida, Masahito Shimizu, Makiko Taniai, Shuji Terai, Hiroki Nishikawa, Yoichi Hiasa, Hisashi Hidaka, Hiroto Miwa, Kazuaki Chayama, Nobuyuki Enomoto, Tooru Shimosegawa, Tetsuo Takehara, Kazuhiko Koike
    Journal of gastroenterology 56 7 593 - 619 2021年07月 
    The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
  • Masafumi Ohira, Hideki Yokoo, Koji Ogawa, Moto Fukai, Toshiya Kamiyama, Naoya Sakamoto, Akinobu Taketomi
    Carcinogenesis 42 6 794 - 803 2021年06月21日 [査読有り]
     
    Fatty acid-binding protein 5 (FABP5) is highly expressed in hepatocellular carcinoma (HCC) tissues and is related to HCC progression. In this study, we analyzed the potential of serum FABP5 (sFABP5) as a tumor marker in HCC and its clinical significance in HCC progression. We compared the sFABP5 concentration in patients with HCC (HCC group) with that of patients with hepatitis without HCC (hepatitis group). Moreover, we measured the FABP5 expression levels in resected HCC tissues (tFABP5) and analyzed their relationship with sFABP5. We also performed cell-based assays using FABP5 knockout and overexpressing HCC cell lines to analyze the effect of extrinsic FABP5 (exFABP5) on HCC cells. We showed that sFABP5 was not a useful tumor marker for HCC, as HCC and sFABP5 were not correlated. However, sFABP5 and tFABP5 significantly correlated with survival after surgery for HCC, while sFABP5 and tFABP5 were independent of each other. In cell-based assays, exFABP5 was taken up by HCC cell lines and positively affected cell survival under glucose-depleted conditions by complementing the endogenous FABP5 function. In conclusion, sFABP5 had a significant impact on HCC progression irrespective of tFABP5 by augmenting cell viability under glucose-depleted conditions. As tFABP5 and sFABP5 are important factors that are independent of each other in HCC progression, both of them should be considered independently in improving the prognosis of patients with HCC.
  • Osamu Maehara, Goki Suda, Mitsuteru Natsuizaka, Taku Shigesawa, Gouki Kanbe, Megumi Kimura, Masaya Sugiyama, Masashi Mizokami, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Shinya Ohashi, Shingo Kagawa, Hideaki Kinugasa, Seiji Naganuma, Naoto Okubo, Shunsuke Ohnishi, Hiroshi Takeda, Naoya Sakamoto
    Cancer biology & therapy 22 5-6 372 - 380 2021年06月03日 [査読有り]
     
    Fibroblast growth factors (FGFs) and their receptors (FGFRs) are important for signaling to maintain cancer stem-like cells (CSCs) in esophageal squamous cell carcinoma (ESCC). However, which FGF receptor, 1, 2, 3, 4, and L1, is essential or whether FGFRs have distinct different roles in ESCC-CSCs is still in question. This study shows that FGFR2, particularly the IIIb isoform, is highly expressed in non-CSCs. Non-CSCs have an epithelial phenotype, and such cells are more differentiated in ESCC. Further, FGFR2 induces keratinocyte differentiation through AKT but not MAPK signaling and diminishes CSC populations. Conversely, knockdown of FGFR2 induces epithelial-mesenchymal transition (EMT) and enriches CSC populations in ESCC. Finally, data analysis using The Cancer Genome Atlas (TCGA) dataset shows that expression of FGFR2 significantly correlated with cancer cell differentiation in clinical ESCC samples. The present study shows that each FGFR has a distinct role and FGFR2-AKT signaling is a key driver of keratinocyte differentiation in ESCC. Activation of FGFR2-AKT signaling could be a future therapeutic option targeting CSC in ESCC.
  • Yoshimasa Tokuchi, Goki Suda, Megumi Kimura, Osamu Maehara, Takashi Kitagataya, Masatsugu Ohara, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    Journal of viral hepatitis 28 5 755 - 763 2021年05月 [査読有り]
     
    Hepatitis C virus (HCV) infection can cause renal dysfunction, expected to improve upon HCV eradication. However, adverse effects of HCV eradication using direct-acting antiviral agents (DAAs) on renal function have been recently reported. This retrospective study aimed to evaluate renal function with glomerular filtration rate (eGFR) estimated using creatinine (eGFRcre) and cystatin C (eGFRcys). Complete clinical information and preserved serum samples were collected from 207 patients with HCV infection treated with interferon-free DAA at baseline and SVR48 (SVR48). Patients who underwent paired computed tomography (CT) at baseline and ≥12 months after DAA were evaluated for changes in skeletal muscle mass using the psoas muscle mass index (PMI). eGFRcre significantly worsened at SVR48, while eGFRcys was similar at baseline and SVR48. At baseline, eGFRcre was significantly higher than eGFRcys; eGFRcre and eGFRcys were similar at SVR48. Multivariate analysis revealed that the presence of liver cirrhosis and low-albumin level, as well as cirrhosis and age, was significantly associated with the overestimation of renal function by eGFRcre at baseline and SVR48, respectively. In the 57 patients who underwent paired CT at baseline and ≥12 months after DAA, relative values of PMI significantly increased after DAA. After DAA, in patients with increased PMI (65% 37/57), eGFRcre significantly worsened but did not change in patients without increased PMI. eGFRcre significantly worsened after DAAs; however, this might not reflect accurate changes in renal function, partially because of changes in skeletal muscle mass. eGFRcys did not change after DAAs, and it is a potential alternative to eGFRcre.
  • Naoki Kawagishi, Goki Suda, Megumi Kimura, Osamu Maehara, Ren Yamada, Yoshimasa Tokuchi, Akinori Kubo, Takashi Kitagataya, Taku Shigesawa, Kazuharu Suzuki, Masatsugu Ohara, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Yusuke Kudo, Mutsumi Nishida, Naoya Sakamoto
    Scientific reports 11 1 9207 - 9207 2021年04月28日 [査読有り]
     
    We previously revealed that Angiopoietin-2 (Ang2) predicts non-regression of liver fibrosis based on liver stiffness measurement (LSM) at 24 weeks after anti-hepatitis C virus (HCV) treatment. In this study, we extended the observational period to 96 weeks to investigate the factors associated with non-regression after treatment with direct-acting-antivirals (DAAs). Patients treated with DAAs who underwent transient elastography at baseline and 24 and 96 weeks after DAA therapy were included. Baseline and post-treatment serum Ang2 levels were measured. Liver fibrosis stages were defined based on LSM. Multivariate regression was used to evaluate factors associated with non-regression of liver fibrosis between various time points. In total, 110 patients were included. Of these, 11% showed non-regression of LSM-based fibrosis stage at 96 weeks after DAA therapy. In multivariate analysis, advanced liver fibrosis stage and high baseline Ang2 levels were significantly associated with non-regression at 96 weeks. In patients with advanced liver fibrosis (F3/4), baseline Ang2 levels were associated with non-regression of liver fibrosis stage. Between SVR24 and SVR96, post-treatment Ang2 levels and controlled attenuation parameter values at SVR24 were significantly associated with non-regression of liver fibrosis stage in patients with F3/4. Thus, serum Ang2 levels are an important target for monitoring and therapy.
  • 須田 剛生, 小川 浩司, 坂本 直哉
    肝臓 62 4 209 - 211 一般社団法人 日本肝臓学会 2021年04月01日 [査読無し]
  • Kazuharu Suzuki, Goki Suda, Yoshiya Yamamoto, Ken Furuya, Masaru Baba, Akinobu Nakamura, Hideaki Miyoshi, Megumi Kimura, Osamu Maehara, Ren Yamada, Takashi Kitagataya, Koji Yamamoto, Taku Shigesawa, Akihisa Nakamura, Masatsugu Ohara, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
    Journal of gastroenterology 56 2 168 - 180 2021年02月 [査読有り]
     
    BACKGROUND: Entecavir and tenofovir-disoproxil-fumarate are first-line nucleos(t)ide analogs (NA) for treatment of hepatitis B virus (HBV) infections; however, their long-term administration can impact extrahepatic organs. Herein, we sought to examine the effect of NA on lipid metabolism while also characterizing the associated mechanism. METHODS: A retrospective study was performed on HBV patients administered entecavir or tenofovir-disoproxil-fumarate. Patient clinical information, as well as their preserved serum samples obtained at baseline and 6-12 months after treatment initiation, were analyzed. A 1:1 propensity score matching was applied to the assignment of tenofovir-disoproxil-fumarate or entecavir treatment. Changes in serum cholesterol, including oxidized-LDL, were analyzed. Subsequently, in vitro analysis elucidated the mechanism associated with the effect of NAs on lipid metabolism. RESULTS: Administration of tenofovir-disoproxil-fumarate, not entecavir, to chronic HBV patients, decreased serum cholesterol levels, including non-HDL and oxidized-LDL, which are strongly associated with arteriosclerosis. In vitro analysis revealed that tenofovir-disoproxil-fumarate reduced supernatant cholesterol, and upregulated the scavenger receptor, CD36, in hepatocytes. Meanwhile, silencing of hepatic CD36 increased supernatant cholesterol and negated the cholesterol-reducing effect of tenofovir-disoproxil-fumarate in HepG2-cells. Reporter, microarray, and RT-PCR analyses further revealed that tenofovir-disoproxil-fumarate treatment activates PPAR-α-mediated signaling, and upregulates PPAR-α target genes, including CPT1 and CD36. Alternatively, silencing of PPAR-α reversed the effects of tenofovir-disoproxil-fumarate on CD36. CONCLUSIONS: Tenofovir-disoproxil-fumarate modulates lipid metabolism by upregulating hepatic CD36 via PPAR-α activation. Since dyslipidemia could be associated with arteriosclerosis and hepatocarcinogenesis, these discoveries provide novel insights into anti-HBV therapies, as well as the associated extrahepatic effects of NA.
  • Isao Hidaka, Masaru Enomoto, Syuichi Sato, Atsushi Suetsugu, Tomomitsu Matono, Kiyoaki Ito, Koji Ogawa, Jun Inoue, Mika Horino, Yasuteru Kondo, Isao Sakaida, Masaaki Korenaga
    Internal medicine (Tokyo, Japan) 60 3 337 - 343 2021年 [査読有り]
     
    Objective Persistent hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major causative factors of hepatic cirrhosis and hepatocellular carcinoma. However, the development of antiviral treatment has enabled their suppression. Therefore, the early detection and treatment of these infections are important. The objective of this study was to assess the level of awareness among healthcare professionals about hepatitis virus infection and electronic medical records alert system. Methods We surveyed healthcare professionals from 10 institutions with electronic medical records alert systems. All participants attended a lecture about the reactivation risk due to HBV infections, the most recent antiviral treatment for HCV infections, and the electronic medical records alert system. They participated in a questionnaire-based survey about their awareness of these infections, current status of intra-hospital referral, need for intra-hospital referrals before and after the lecture, and reasons for non-referral of patients to specialists. Results Responses were received from 1,281 healthcare professionals. Physicians and pharmacists had a high level of awareness about HBV and HCV. Among physicians, the level of awareness of those in the surgical field and other fields was significantly lower than that of the professionals in the internal medicine field. The awareness of the need to refer patients to hepatologists increased from 84.7-85.4% before to 93.0% after the lecture. The most frequent reasons for not referring patients previously were "I had no knowledge and/or interest" (28.1% of responses) and "All I did was explain the results orally" (24.2%). Conclusion More widespread education of healthcare personnel is important to increase the number of individuals receiving appropriate treatment from specialist physicians.
  • Taku Shigesawa, Goki Suda, Megumi Kimura, Osamu Maehara, Yoshimasa Tokuchi, Akinori Kubo, Ren Yamada, Ken Furuya, Masaru Baba, Takashi Kitagataya, Kazuharu Suzuki, Masatsugu Ohara, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    PloS one 16 3 e0247728  2021年 [査読有り]
     
    A deteriorated liver functional reserve during systemic therapy for unresectable hepatocellular carcinoma (HCC) causes poor patient outcomes. We aimed to identify predictive factors associated with the deterioration of Child-Pugh score at 8 weeks after lenvatinib initiation. Patients with adequate clinical data and baseline preserved serum samples available were included. Baseline fibroblast growth factor (FGF)19 and 21, angiopoietin (ANG)2, and vascular endothelial growth factor (VEGF) levels were evaluated. Thirty-seven patients were included, and 6, 15, 14, and 2 experienced complete response, partial response, stable disease, and progressive disease, respectively. Twenty-four (65%) and 13 (35%) patients showed a maintained/improved and deteriorated Child-Pugh-score, respectively. While baseline clinical data, treatment response, and laboratory data were similar between these two patient groups, baseline ANG2 and VEGF levels were significantly higher (P = 0.0017) and lower (P = 0.0231), respectively, in patients with deteriorated Child-Pugh score than in those without. Based on receiver operating characteristic curve analysis, cut-off values for ANG2 and VEGF were found to be 3,108 pg/mL and 514.9 pg/mL, respectively. Among patients with low VEGF and high ANG2, 89% (8/9) exhibited a deteriorated Child-Pugh score, whereas none of the patients (0/9) with high VEGF and low ANG2 did. The deterioration of the Child-Pugh score in patients with unresectable HCC who are treated with lenvatinib may be predictable based on combined baseline serum ANG2 and VEGF levels.
  • Masato Nakai, Goki Suda, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Naoki Kawagishi, Masatsugu Ohara, Machiko Umemura, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    Journal of gastroenterology 55 12 1150 - 1161 2020年12月 [査読有り]
     
    BACKGROUND: Decompensated liver cirrhosis patients with refractory ascites or pleural effusion have a poor prognosis. Tolvaptan has been used for treating water retention associated with cirrhosis. However, despite the short-term response, water retention recurrence is still observed in some cases. This study aimed to clarify the water retention recurrence rate and the relationship between long-term response without recurrence and prognosis. METHODS: Altogether, 100 patients with decompensated cirrhosis treated with tolvaptan were retrospectively analyzed. Recurrence was evaluated according to the criteria of the EASL clinical practice guideline. The recurrence rate and prognosis of non-responders, patients with recurrence, and long-term responders were analyzed. The baseline factors related to short-term response, recurrence, and long-term response were also evaluated. RESULTS: Approximately 31.0% of the short-term responders had recurrence. Although there was no significant difference in the prognosis by short-term response (p = 0.07), the long-term responders had a significantly better prognosis than those with recurrence and non-responders (p < 0.01). Low CRP levels and high urinary Na/K ratios were significant factors related to short-term response, and the presence of acute kidney injury was also a factor related to non-response. The low CRP level (relapse: < 1.10 mg/dl, long-term response: < 0.94 mg/dl) was identified as a factor related to recurrence and long-term response. CONCLUSION: The long-term responders without recurrence had a significantly better prognosis. CRP was a useful predictor for long-term response, whereas renal function parameters were useful predictors for short-term response. Inflammation control may be important for long-term response and prognosis in cirrhosis patients with water retention.
  • Takashi Kitagataya, Goki Suda, Kazunori Nagashima, Takehiko Katsurada, Koji Yamamoto, Megumi Kimura, Osamu Maehara, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Yoshito Komatsu, Hiroo Hata, Satoshi Takeuchi, Takashige Abe, Jun Sakakibara-Konishi, Takanori Teshima, Akihiro Homma, Naoya Sakamoto
    Journal of gastroenterology and hepatology 35 10 1782 - 1788 2020年10月 [査読有り]
     
    BACKGROUND AND AIM: Immune checkpoint inhibitors (ICI) have revolutionized anti-malignancy therapy and thus have been increasingly used. Although ICI may cause immune-related adverse events (irAE) in various organs, including the liver, the prevalence and predictive factors of irAE have not been clarified. METHODS: In this retrospective study, consecutive patients who had malignancies and were treated with ICI without other chemotherapeutic agents at Hokkaido University Hospital between 2014 and 2019 were screened. Patients were excluded if they were < 20 years old and had insufficient clinical data. RESULTS: Of the 233 patients screened, 202 patients met the inclusion criteria and were included in the analysis. The patients were aged 25-92 years, and 60.9% were male. The patients received nivolumab (n = 137), pembrolizumab (n = 45), ipilimumab (n = 17), atezolizumab (n = 2), and avelumab (n = 1). The prevalence of any grade and grade ≥ 3 irAE hepatitis was 8.4% (17/202) and 4.0% (8/202), respectively. irAE hepatitis occurred at a median duration of 42 days in any grade and 36 days in grade ≥ 3 after ICI initiation. The clinical course of grade ≥ 3 irAE hepatitis was generally favorable; however, 50% required corticosteroid treatment and two patients required additional mycophenolate mofetil. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis. CONCLUSIONS: Grade ≥ 3 irAE hepatitis was observed in 4.0% of the patients who were treated with ICI. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis.
  • Goki Suda, Koji Ogawa, Megumi Kimura, Osamu Maehara, Takashi Kitagataya, Masatsugu Ohara, Yoshimasa Tokuchi, Akinori Kubo, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 50 10 1196 - 1200 2020年10月 [査読有り]
     
    AIM: Coronavirus disease 2019 (COVID-19) is a serious public health concern, with unclarified prevalence in Japan. Concomitant liver disease could increase the severity of COVID-19 disease, and chronic liver disease patients sometimes require frequent admission and gastrointestinal endoscopy. Thus, clarifying the prevalence of asymptomatic COVID-19 in outpatients with liver disease is essential for preventing nosocomial infections. We aimed to clarify the time-dependent changes in COVID-19 seroprevalence in liver disease outpatients, who were asymptomatic for COVID-19, in an area of Japan experiencing a second wave of COVID-19. METHODS: We included the preserved sera of 100, 300, and 300 consecutive liver disease outpatients, who were asymptomatic for COVID-19, from May 2019, March 2020, and May 2020, respectively. The sera were analyzed immunochromatographically to detect immunoglobulin G against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (KURABO) and by Elecsys Anti-SARS-CoV-2-assay (Roche Diagnostics). RESULTS: Analysis of 100 cases from May 2019, before COVID-19 became pandemic, revealed that the specificity of immunochromatographic tests and Elecsys were 98% (95% confidence interval [CI], 93-99.8%) and 100% (95% CI, 97-100%), respectively. Analysis of 300 cases from March 2020 revealed a seroprevalence of 0.3% (1/300; 95% CI, 0-1.8%) for COVID-19 by Elecsys Anti-SARS-CoV-2 assay. Analysis of 300 cases from May 2020 revealed a seroprevalence of 0% (0/300; 95% CI, 0-1.0%). CONCLUSIONS: The Elecsys Anti-SARS-CoV-2 assay has high specificity. The cumulative seroprevalence of COVID-19 by the Elecsys Anti-SARS-CoV-2 assay in outpatients with liver disease in Sapporo, who were asymptomatic for COVID-19, was 0.17% (1/600; 95% CI, 0.0-0.9%) until May 2020.
  • Kosuke Saito, Tatehiro Kagawa, Keiji Tsuji, Yuji Kumagai, Ken Sato, Shotaro Sakisaka, Naoya Sakamoto, Mitsuhiko Aiso, Shunji Hirose, Nami Mori, Rieko Tanaka, Toshio Uraoka, Kazuhide Takata, Koji Ogawa, Kazuhiko Mori, Motonobu Sato, Takayoshi Nishiya, Kazuhiko Takamatsu, Noriaki Arakawa, Takashi Izumi, Yasuo Ohno, Yoshiro Saito, Hajime Takikawa
    Metabolites 10 9 2020年08月31日 [査読有り]
     
    Drug-induced liver injury (DILI) is a major adverse event caused by drug treatment, which can be categorized into three types: hepatocellular, mixed, and cholestatic. Although nearly every class of drugs can cause DILI, an overall understanding of lipid profiles in DILI patients is lacking. We used lipidomics to analyze the plasma lipid profiles of patients to understand their hepatic pathophysiology and identify DILI biomarkers. We identified 463 lipids and compared their levels between the acute and recovery phases of the three types of DILI patients. Mixed and cholestatic types demonstrated specific plasma lipid alterations between the phases, but the hepatocellular type did not. Moreover, as specific indicators of mixed-type DILI, levels of several ceramides increased in the acute phase, while those of arachidonic acid-containing ether-linked phosphoglycerolipids decreased. In contrast, as specific indicators of cholestatic-type DILI, levels of palmitic acid-containing saturated or monounsaturated phosphatidylcholines increased in the acute phase, while those of arachidonic acid- or docosahexaenoic acid-containing ether-linked phosphoglycerolipids and phosphatidylinositols decreased. We also identified lipids with a relatively high capacity to discriminate the acute phase from the recovery phase and healthy subjects. These findings may help with understanding the pathophysiology of different DILI types and identify candidate biomarkers.
  • Masatsugu Ohara, Goki Suda, Megumi Kimura, Osamu Maehara, Tomoe Shimazaki, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    JCSM Rapid Communications 3 2 103 - 114 2020年07月
  • Takuya Sho, Goki Suda, Koji Ogawa, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Jun Ito, Yoshiya Yamamoto, Tomoe Kobayashi, Takashi Meguro, Akiyoshi Saga, Takuto Miyagishima, Katsumi Terasita, Tomofumi Takagi, Toshiya Kamiyama, Akinobu Taketomi, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 50 8 966 - 977 2020年06月20日 [査読有り][通常論文]
     
    AIM: This study aimed to determine the efficacy and safety of lenvatinib for patients with unresectable hepatocellular carcinoma (HCC) who did not meet REFLECT eligibility criteria (phase 3 clinical trial). METHODS: In this multicenter retrospective study, patients with unresectable HCC treated with lenvatinib between 2018 and 2019 and had adequate clinical data were included. Objective-response-rate (ORR), progression-free-survival (PFS), and safety were evaluated according to meeting or not meeting the REFLECT eligibility criteria and according to the criteria of the REFLECT trial. RESULTS: Of the 105 patients included, 61% (64/105) did not meet the REFLECT eligibility criteria. Safety and median PFS of lenvatinib were similar between the patients who did and those who did not meet the criteria. Among the patients who did not meet the criteria, 28, 27, 14, 6, 7, and 5 had a history of tyrosine kinase inhibitor (TKI) treatment, Child-Pugh score B, HCC in ≥50% of the liver, reduced platelet count, bile duct invasion, and main portal vein invasion. The efficacy and safety of lenvatinib for patients with or without Child-Pugh-score B or HCC in ≥50% of the liver were similar. Although treatment outcome was not significantly different, patients with TKI treatment history tended to have longer median PFS, whereas those with main portal vein invasion tended to have shorter median PFS. CONCLUSION: Lenvatinib was effective for patients who did not meet the REFLECT inclusion criteria. However, the treatment outcome may vary according to several factors, such as a history of TKI treatment and tumor invasion.
  • Taku Shigesawa, Osamu Maehara, Goki Suda, Mitsuteru Natsuizaka, Megumi Kimura, Tomoe Shimazaki, Koji Yamamoto, Ren Yamada, Takashi Kitagataya, Akihisa Nakamura, Kazuharu Suzuki, Masatsugu Ohara, Naoki Kawagishi, Machiko Umemura, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Masaya Sugiyama, Masashi Mizokami, Hiroshi Takeda, Naoya Sakamoto
    Carcinogenesis 42 1 58 - 69 2020年05月25日 [査読有り][通常論文]
     
    In hepatocellular carcinoma (HCC), a subset of cells defined by high CD44 and CD133 expression has been reported to possess cancer stem-like cell (CSC) characteristics and to be associated with a poor prognosis. Since the approval of the multi-kinase inhibitor, lenvatinib, for patients with unresectable HCC, two such inhibitors (sorafenib and lenvatinib) have been employed as first-line systemic chemotherapeutics for these patients. Based on differences in the kinase-affinity profiles between these two drugs, evidence has suggested that both exert different effects on HCC, although these differences are not fully characterized. In this study, using in vitro and a preclinical in vivo xenograft mouse model, we showed that lenvatinib alone (not sorafenib or the cytotoxic agent, 5-fluorouracil) diminished CD44High/CD133High CSCs in HCC. Furthermore, western blotting and RT-PCR analysis revealed that the expression of fibroblast growth factor receptor (FGFR)-1 to 4 differed between CD44High/CD133High CSCs and control cells. Analysis of the effects of selective FGFR inhibitors and FGFR small interfering RNAs on CSCs in HCC revealed that lenvatinib diminished CSCs in HCC by inhibiting FGFR1-3 signaling, however, FGFR4 signaling was not impacted. Finally, we showed that FGF2 and FGF19 were involved in maintaining CD44High/CD133High CSCs in HCC, potentially, via FGFR1-3. The findings provide novel mechanistic insights into the effects of lenvatinib on CSCs in HCC and provide clues for developing effective targeted therapies against CSCs in HCC.
  • Taku Shigesawa, Goki Suda, Megumi Kimura, Tomoe Shimazaki, Osamu Maehara, Ren Yamada, Takashi Kitagataya, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    JGH OPEN 4 5 880 - 888 2020年04月 [査読有り][通常論文]
     
    Background Sorafenib and lenvatinib are first-line systemic therapies for unresectable hepatocellular carcinoma (HCC). However, the criteria for their selection remain unclear.Methods We identified patients with unresectable HCC who were treated with sorafenib or lenvatinib between August 2009 and January 2019 at the Hokkaido University Hospital. Patients who continued treatment for >2 months, underwent evaluation by computed tomography every 2-3 months, and had complete clinical data were included. Responders were patients with objective response (OR) for lenvatinib and patients with stable disease (SD) exceeding 6 months (long-SD) or OR for sorafenib. The predictive factors for treatment response, including fibroblast growth factor (FGF)19 and 21, angiopoietin 2 (ANG2), hepatocyte growth factor, and vascular endothelial growth factor, were evaluated.Results Overall, 27 and 29 patients treated with lenvatinib and sorafenib, respectively, were included. The responders for lenvatinib and sorafenib were 63% (17/27) and 38% (11/29), respectively. No significant predictive factors for treatment response were identified in patients treated with sorafenib. However, baseline serum FGF19 and ANG2 levels were significantly associated with treatment response to lenvatinib. All (9/9) patients with low baseline ANG2 and FGF19 levels who received lenvatinib achieved OR. Conversely, the OR was low (13%; 1/9) in patients with high baseline ANG2 and FGF19 levels. Responder rate was 40% (2/5) in patients with high baseline ANG2 and FGF19 levels who received sorafenib.Conclusion This study is, to our knowledge, the first to demonstrate that baseline ANG2 and FGF19 levels may aid in selecting optimal systemic therapy for patients with unresectable HCC.
  • Masatsugu Ohara, Goki Suda, Megumi Kimura, Osamu Maehara, Tomoe Shimazaki, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Tomoe Kobayashi, Minoru Uebayashi, Ryo Takagi, Isao Yokota, Tsuyoshi Shimamura, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 50 6 715 - 725 2020年03月23日 [査読有り][通常論文]
     
    This study aimed to determine the optimal psoas muscle mass index (PMI) cut-off values for diagnosis of skeletal muscle mass loss. METHODS: We evaluated PMI in two groups of normal controls: a medical check-up group and a liver donation candidate group. We analyzed two novel PMI cut-off values, one based on the mean - two standard deviations (2SD) and one based on the lower 5%. Skeletal muscle mass index (SMI) evaluations using computed tomography (sliceOmatic; TomoVision) and bioelectrical impedance analysis and PMI evaluation were undertaken simultaneously. We analyzed the correlation between our PMI cut-off values and the Japan Society of Hepatology-defined SMI cut-off values. The prevalence of skeletal muscle mass loss in patients with liver disease was assessed using the novel PMI cut-off values. RESULTS: In 504 normal controls aged ≤50 years, the PMI cut-off values based on mean -2SD and the lower 5% were set at 3.30 cm2 /m2 for men and 1.69 cm2 /m2 for women and 3.74 cm2 /m2 for men and 2.29 cm2 /m2 for women, respectively. The PMI cut-off values based on the lower 5% alone showed that skeletal muscle mass loss increased with age. Furthermore, they correlated well with Japan Society of Hepatology-defined SMI (sliceOmatic) cut-off values and showed a significantly higher prevalence of skeletal muscle mass loss in patients with liver cirrhosis than those without liver cirrhosis. CONCLUSIONS: We propose the following PMI cut-off values: 3.74 cm2 /m2 for male individuals and 2.29 cm2 /m2 for female individuals. These cut-off values can facilitate accurate diagnosis and management of sarcopenia in patients with chronic liver disease.
  • Naoki Kawagishi, Goki Suda, Megumi Kimura, Osamu Maehara, Tomoe Shimazaki, Ren Yamada, Takashi Kitagataya, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Yusuke Kudo, Mutsumi Nishida, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 2020年02月05日 [査読有り][通常論文]
     
    AIM: Factors associated with improvement of liver fibrosis after successful hepatitis C virus (HCV) eradication by interferon (IFN)-free direct-acting antiviral agents (DAAs) have been not clarified well. Angiopoietin-2 (Ang2) is reported to be associated with vascular leak and inflammation observed in patients with advanced liver fibrosis. METHODS: In this retrospective study, patients treated with IFN-free DAAs who underwent transient elastography before and at 24-weeks post-treatment and achieved sustained viral response were enrolled. Baseline serum Ang2 was measured, and its relationship with other clinical factors was analyzed. Liver fibrosis stage was defined based on liver stiffness according to a previous report. Predictive factors for regression of liver fibrosis stage after DAA therapy were evaluated. RESULTS: Overall, 116 patients were analyzed. Baseline serum Ang2 levels were significantly associated with liver stiffness, spleen index, and liver stiffness-based liver fibrosis stage. Moreover, 75% of patients experienced regression of liver fibrosis stage after DAA therapy. Multivariate analysis revealed that advanced liver fibrosis stage and Ang2 levels were significantly associated with regression of liver fibrosis stage after DAA therapy. In patients with advanced liver fibrosis (F3/4), baseline Ang2 level alone could predict regression of liver fibrosis stage. A baseline Ang2 cut-off value (354 pg/ML) could predict regression of liver fibrosis stage after DAA therapy with high accuracy (sensitivity 0.882, specificity 0.733). CONCLUSIONS: Evaluation of serum Ang2 levels before DAA therapy is important. Our results provide a novel mechanistic insight into non-regression of liver stiffness after DAA therapy. Long-term and larger studies are required.
  • Hiroshi Yotsuyanagi, Tomoko Takano, Motofumi Tanaka, Keisuke Amano, Michio Imamura, Koji Ogawa, Tetsuya Yasunaka, Yutaka Yasui, Kazuhiko Hayashi, Yasuhito Tanaka, Hitoshi Tajiri
    Hepatology research : the official journal of the Japan Society of Hepatology 50 2 182 - 189 2020年02月 [査読有り]
     
    AIM: Hepatitis B vaccination in infancy was carried out in Japan only when the mother was persistently infected from 1986 to 2016. The aim of the present study was to elucidate the results of vaccination for the prevention of hepatocellular carcinoma in young adults. METHODS: We studied the number of patients who had liver cancer and died from 1976 to 2017 using a national database. Furthermore, we carried out a nationwide survey focusing on patients with hepatitis B virus-related hepatocellular carcinoma who were diagnosed when aged <40 years from 2007 to 2016. RESULTS: The national database showed that the number of deaths of patients aged <40 years decreased from 337 in 1986 to 61 in 2016. Among the 122 patients with hepatocellular carcinoma (HCC) who were registered in the survey, just three patients were born after the start of the vaccination in 1986. Liver cirrhosis, defined by a high Fib-4 index (≥3.25), was found in just 12.5% of the patients at the time of the survey. HCC was incidentally diagnosed in 85 of the 122 (69%) patients. More than 60% of the patients (54/88) were dead at the time of the study, which may be attributed to the delay in diagnosis. CONCLUSIONS: Selective vaccination was effective for the prevention of hepatitis B virus-related HCC. In contrast, many young adults who missed the chance of hepatitis B vaccination and HCC surveillance developed HCC and died. Hepatitis B virus screening in young adults and careful follow up of infected patients are important to prevent HCC development.
  • Takuya Sho, Goki Suda, Koji Ogawa, Megumi Kimura, Tomoe Shimazaki, Osamu Maehara, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Tomoe Kobayashi, Takashi Meguro, Akiyoshi Saga, Takuto Miyagishima, Hideki Yokoo, Toshiya Kamiyama, Akinobu Taketomi, Naoya Sakamoto
    JGH open : an open access journal of gastroenterology and hepatology 4 1 54 - 60 2020年02月 [査読有り][通常論文]
     
    Background and Aim: Lenvatinib has been recently approved as a first-line systematic therapy for patients with advanced hepatocellular carcinoma (HCC) based on the results of the phase 3 clinical trial REFLECT. This trial excluded patients with a history of systemic chemotherapy, bile duct invasion, and Child-Pugh grade B. We aimed to investigate the efficacy and safety of lenvatinib for these patients and in the real-world setting. Methods: Among patients who were administered lenvatinib for advanced HCC between April and October 2018 in Hokkaido University Hospital and related hospitals, we evaluated those who were followed for more than 2 months and whose treatment response was evaluated via dynamic computed tomography at baseline and 2 months after treatment initiation. Meanwhile, patients were excluded if they had decompensated liver cirrhosis, were followed up less than 2 months, or were not evaluated at 2 months. Patients were also stratified according to compliance with the REFLECT inclusion criteria for further analysis. Results: A total of 41 patients were included; more than 50% did not meet the REFLECT inclusion criteria. In total, 5 (12.2%), 20 (48.8%), 12 (29.3%), and 4 (9.3%) showed complete response, partial response, stable disease, and progressive disease, respectively. The objective response rate was 61.2%. The objective response rate and disease control rate were similar between patients who did and did not meet the REFLECT inclusion criteria. Moreover, the safety profile was also similar between the two patient groups. Conclusion: Lenvatinib showed high early response rate and tolerability in patients with advanced HCC. Favorable outcomes were similarly observed in patients who did not meet the REFLECT inclusion criteria.
  • Koji Ogawa, Takashi Kobayashi, Jun-Ichi Furukawa, Hisatoshi Hanamatsu, Akihisa Nakamura, Kazuharu Suzuki, Naoki Kawagishi, Masatsugu Ohara, Machiko Umemura, Masato Nakai, Takuya Sho, Goki Suda, Kenichi Morikawa, Masaru Baba, Ken Furuya, Katsumi Terashita, Tomoe Kobayashi, Manabu Onodera, Takahiro Horimoto, Keisuke Shinada, Seiji Tsunematsu, Izumi Tsunematsu, Takashi Meguro, Tomoko Mitsuhashi, Megumi Hato, Kenichi Higashino, Yasuro Shinohara, Naoya Sakamoto
    Scientific reports 10 1 321 - 321 2020年01月15日 [査読有り][通常論文]
     
    Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) that may lead to liver cirrhosis or hepatocellular carcinoma. Here, we examined the diagnostic utility of tri-antennary tri-sialylated mono-fucosylated glycan of alpha-1 antitrypsin (AAT-A3F), a non-invasive glycobiomarker identified in a previous study of NASH diagnosis. This study included 131 biopsy-proven Japanese patients with NAFLD. We evaluated the utility of AAT-A3F in NASH diagnosis, and conducted genetic analysis to analyse the mechanism of AAT-A3F elevation in NASH. Serum AAT-A3F concentrations were significantly higher in NASH patients than in NAFL patients, and in patients with fibrosis, lobular inflammation, and ballooning. Hepatic FUT6 gene expression was significantly higher in NASH than in NAFL. IL-6 expression levels were significantly higher in NASH than in NAFL and showed a positive correlation with FUT6 expression levels. The serum-AAT-A3F levels strongly correlated with hepatic FUT6 expression levels. AAT-A3F levels increased with fibrosis, pathological inflammation, and ballooning in patients with NAFLD and may be useful for non-invasive diagnosis of NASH from the early stages of fibrosis.
  • Tatsuhiko Sakamoto, Yoshitaka Saito, Masaki Kobayashi, Takehiro Yamada, Yoh Takekuma, Masato Nakai, Koji Ogawa, Ken Iseki, Mitsuru Sugawara
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2019年11月16日 [査読有り][通常論文]
     
    PURPOSE: There are several studies on premedication to prevent postembolization syndromes which occurs after transcatheter arterial chemoembolization (TACE), but the medication to be used is still not established. This study aimed to examine the effect of palonosetron and dexamethasone on the prevention of gastrointestinal symptoms induced by TACE. METHODS: Patients with hepatocellular carcinoma who were treated with TACE with epirubicin were retrospectively evaluated. The complete response rate of antiemetic drugs and incidence and severity of gastrointestinal symptoms were compared between the antiemetic group (AE group), which includes 51 patients prophylactically administered with palonosetron 0.75 mg and dexamethasone 9.9 mg intravenously before TACE on day 1 and dexamethasone 6.6 mg intravenously on days 2 and 3, and control group with 101 patients without antiemetic premedication. RESULTS: Complete response rate in the entire evaluation period was significantly higher in the AE group compared with that in the control group. In the acute phase, the incidence and severity of nausea, vomiting, and anorexia significantly decreased in the AE group, but only anorexia improved in the delay phase. Additionally, postembolization syndromes, such as abdominal pain and fever, were significantly attenuated in the AE group; however, constipation worsened in this group. CONCLUSIONS: Premedication of palonosetron and dexamethasone significantly prevents the incidence and reduces the severity of gastrointestinal symptoms especially in the acute phase. Further studies will be needed to determine the most recommended 5-HT3 antagonist or dosage of dexamethasone in establishing the optimal antiemetic regimen.
  • Ryo Sugiura, Masaki Kuwatani, Mutsumi Nishida, Koji Hirata, Itsuki Sano, Shin Kato, Kazumichi Kawakubo, Masato Nakai, Takuya Sho, Goki Suda, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    Ultrasound in medicine & biology 45 10 2704 - 2712 2019年10月 [査読有り][通常論文]
     
    No worldwide consensus on the assessment tool for liver functional reserve is currently available. The aim of this study was to evaluate the correlation between liver elasticity of both hepatic lobes and liver functional reserve tests. This prospective observational study comprised 40 patients scheduled for hepatectomy. Liver elasticity was assessed by Virtual Touch Quantification (VTQ). The mean VTQ value for the right and left lobes was defined as the mVTQ. Liver functional reserve was measured with technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin scintigraphy as LHL15 and HH15 and the indocyanine green (ICG) excretion test as ICG-R15 and ICG-K. All examinations were measured after biliary decompression confirmed serum a total bilirubin level ≤2 mg/dL. Mean VTQ values were moderately correlated with LHL15 (r = -0.42, p < 0.01), HH15 (r = 0.48, p < 0.01), ICG-R15 (r = 0.53, p < 0.01) and ICG-K (r = -0.61, p < 0.01) values. In conclusion, the liver elasticity determined by VTQ would be a useful predictor of liver functional reserve in patients scheduled for hepatectomy.
  • Takaaki Izumi, Takuya Sho, Kenichi Morikawa, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Naoki Kawagishi, Machiko Umemura, Tomoe Shimazaki, Megumi Kimura, Masato Nakai, Goki Suda, Mitsuteru Natsuizaka, Koji Ogawa, Yusuke Kudo, Mutsumi Nishida, Kota Ono, Masaru Baba, Ken Furuya, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 49 10 1207 - 1217 2019年10月 [査読有り][通常論文]
     
    AIM: Ultrasound technology can now be used for liver stiffness measurement (LSM) and for evaluating the amount of hepatic fat quantitatively known as the controlled attenuation parameter (CAP). This study aimed to determine the applicable cut-off values of LSM and the CAP for primary hepatocellular carcinoma (HCC), and to investigate their clinical usefulness for assessing HCC risk in patients with chronic liver disease. METHODS: A total of 1054 patients (88 with primary HCC and 966 without HCC) whose LSM and the CAP were measured by transient elastography with clinically evident hepatitis C virus (419 patients), hepatitis B virus (377 patients), and non-alcoholic fatty liver disease (258 patients) were enrolled in this study. Subsequently, a total of 966 patients who did not have HCC initially were followed, and the usefulness of the cut-off values of LSM and CAP for HCC development were evaluated. RESULTS: In hepatitis C virus patients, the incidence of HCC development was significantly higher among those with a combination of LSM ≥8.0 kPa and CAP ≤221 dB/m than among those with other values (log-rank test 0.0239, hazard ratio 2.66, 95%CI 1.07-6.47, P = 0.0362). In non-alcoholic fatty liver disease patients, the incidence of HCC development was significantly higher among those with a combination of LSM ≥5.4 kPa and CAP ≤265 dB/m than among others (log-rank test 0.0040, hazard ratio 8.91, 95% CI 1.47-67.97, P = 0.0192). CONCLUSION: In the hepatitis C virus and non-alcoholic fatty liver disease groups, a combination of LSM and the CAP cut-off values would be useful for screening to identify the high-risk group for primary HCC development.
  • Hanamatsu H, Nishikaze T, Tsumoto H, Ogawa K, Kobayashi T, Yokota I, Morikawa K, Suda G, Sho T, Nakai M, Miura N, Higashino K, Sekiya S, Iwamoto S, Miura Y, Furukawa JI, Tanaka K, Sakamoto N
    Analytical chemistry 91 21 13343 - 13348 2019年10月 [査読有り][通常論文]
     
    Sialic acids form the terminal sugars in glycan chains on glycoproteins via α2,3, α2,6, or α2,8 linkages, and structural isomers of sialyl linkages play various functional roles in cell recognition and other physiological processes. We recently developed a novel procedure based on sialic acid linkage-specific alkylamidation via lactone ring opening (aminolysis-SALSA). Herein, we have investigated an isotope labeling of α2,3-linked sialic acid residues (iSALSA) using amine hydrochloride salts. One limitation of SALSA using amine hydrochloride salts may be solved by adding only tert-butylamine (t-BA) as an acid scavenger, and comparative and quantitative glycomic analyses can be performed using iSALSA. We also developed quantitative glycomic analysis using dual isotope-labeled glycans by derivatizing with aminooxy-functionalized tryptophanylarginine methyl ester (aoWR) and iSALSA at the reducing and nonreducing end, respectively. Furthermore, we demonstrate that the amount of α2,3-linked sialoglycans in serum are altered during liver fibrosis using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and liquid chromatography MS (LC/MS) analyses. We revealed that the ratio of A33,6,6 to A3F3,6,6 was gradually decreased along with liver fibrosis progression. Therefore, these glycan alterations are potential diagnostic markers of nonalcoholic steatohepatitis (NASH) fibrosis progression.
  • Naoya Sakamoto, Goki Suda, Kennichi Morikawa, Koji Ogawa
    Journal of gastroenterology and hepatology 34 7 1127 - 1128 2019年07月
  • Suda G, Hasebe C, Abe M, Kurosaki M, Itakura J, Izumi N, Uchida Y, Mochida S, Haga H, Ueno Y, Abe K, Takahashi A, Ohira H, Tsukuda Y, Furuya K, Baba M, Yamamoto Y, Kobayashi T, Inoue J, Terasita K, Ohara M, Kawagishi N, Izumi T, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N, NORTE Study Group
    Journal of gastroenterology 54 7 641 - 649 2019年07月 [査読有り][通常論文]
     
    BackgroundUntil recently, interferon-free anti-hepatitis C virus (HCV) therapy for genotype 2 (GT2) HCV-infected hemodialysis patients was an unfulfilled medical need. Recent clinical trials of glecaprevir and pibrentasvir (G/P) for hemodialysis patients showed high efficacy and safety; however, the number of GT2 HCV-infected patients, especially Asian patients, was limited and most of them were treated with a 12-week regimen. In this prospective multicenter study, we aimed to investigate the efficacy and safety of G/P in Japanese hemodialysis patients with GT2 HCV infection.MethodsTwenty-seven Japanese hemodialysis patients with GT2 HCV infection who were started on with 8- or 12-week G/P regimen between November 2017 and June 2018 were included and followed up for around 12weeks after treatment completion.ResultsAmong the 27 included patients, 13 non-liver cirrhosis (LC) and direct-acting antivirals (DAAs)-naive patients were treated with 8weeks of G/P and 14 patients with LC (n=13) or history of failure of DAAs (n=1) were treated with a 12-week regimen. The overall sustained virological response at 12weeks after treatment completion (SVR 12) was 96.3% (26/27). All patients with 8weeks of treatment achieved SVR12. Two patients discontinued the therapy at 2 and 11weeks after treatment initiation. The patient who discontinued at 2weeks due to pruritus alone failed to respond to G/P. No patients experienced lethal adverse events during the therapy, and the most common adverse event was pruritus.ConclusionsAn 8- or 12-week G/P regimen is highly effective and safe in GT2 HCV-infected hemodialysis patients.
  • Suzuki K, Suda G, Yamamoto Y, Furuya K, Baba M, Kimura M, Maehara O, Shimazaki T, Yamamoto K, Shigesawa T, Nakamura A, Ohara M, Kawagishi N, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N, NORTE Study Group
    Hepatology research : the official journal of the Japan Society of Hepatology 49 11 1294 - 1304 2019年07月 [査読有り][通常論文]
  • Suda G, Kimura M, Shigesawa T, Suzuki K, Nakamura A, Ohara M, Kawagishi N, Nakai M, Sho T, Maehara O, Shimazaki T, Morikawa K, Natsuizaka M, Ogawa K, Sakamoto N
    Hepatology research : the official journal of the Japan Society of Hepatology 49 11 1275 - 1285 2019年07月 [査読有り][通常論文]
  • Kobayashi T, Ogawa K, Furukawa JI, Hanamatsu H, Hato M, Yoshinaga T, Morikawa K, Suda G, Sho T, Nakai M, Higashi-No K, Numata Y, Shinohara Y, Sakamoto N
    Journal of proteome research 2019年07月 [査読有り][通常論文]
  • Suda G, Nakai M, Sho T, Kimura M, Shimazaki T, Maehara O, Shigesawa T, Suzuki K, Nakamura A, Ohara M, Umemura M, Kawagishi N, Baba M, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N, NORTE Study Group
    Internal medicine (Tokyo, Japan) 58 7 943 - 947 2019年04月 [査読有り][通常論文]
  • Chuma M, Toyoda H, Matsuzaki J, Saito Y, Kumada T, Tada T, Kaneoka Y, Maeda A, Yokoo H, Ogawa K, Kamiyama T, Taketomi A, Matsuno Y, Yazawa K, Takeda K, Kunisaki C, Ogushi K, Moriya S, Hara K, Nozaki A, Kondo M, Fukuda H, Numata K, Tanaka K, Maeda S, Sakamoto N
    Hepatology research : the official journal of the Japan Society of Hepatology 49 7 810 - 822 2019年03月 [査読有り][通常論文]
     
    AIMS: Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. METHODS: We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription-polymerase chain reaction (PCR). RESULTS: Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR-1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR-1246 was associated with aggressive tumor characteristics, including tumor-node-metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR-1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528-5.071; P = 0.0008). CONCLUSION: Circulating miR-1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.
  • Sho T, Suda G, Kimura M, Shimazaki T, Maehara O, Shigesawa T, Suzuki K, Nakamura A, Ohara M, Umemura M, Izumi T, Kawagishi N, Baba M, Nakai M, Natsuizka M, Morikawa K, Ogawa K, Sakamoto N, NORTE Study Group
    Internal medicine (Tokyo, Japan) 58 6 797 - 802 2018年11月 [査読有り][通常論文]
  • Kenichi Morikawa, Ogawa Koji, Goki Suda, Naoya Sakamoto
    HEPATOLOGY 68 345A - 345A 2018年10月 [査読有り][通常論文]
  • Nakai Masato, Suda Goki, Ogawa Koji, Suzuki Kazuharu, Nakamura Akihisa, Ohara Masatsugu, Kawagishi Naoki, Umemura Machiko, Sho Takuya, Morikawa Kenichi, Sakamoto Naoya
    HEPATOLOGY 68 843A - 844A 2018年10月 [査読有り][通常論文]
  • Ohara M, Ogawa K, Suda G, Kimura M, Maehara O, Shimazaki T, Suzuki K, Nakamura A, Umemura M, Izumi T, Kawagishi N, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ohnishi S, Sakamoto N
    Hepatology communications 2 8 906 - 918 2018年08月 [査読有り][通常論文]
  • Suda G, Kurosaki M, Itakura J, Izumi N, Uchida Y, Mochida S, Hasebe C, Abe M, Haga H, Ueno Y, Masakane I, Abe K, Takahashi A, Ohira H, Furuya K, Baba M, Yamamoto Y, Kobayashi T, Kawakami A, Kumagai K, Terasita K, Ohara M, Kawagishi N, Umemura M, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N, NORTE Study Group
    Journal of gastroenterology 54 1 78 - 86 2018年07月 [査読有り][通常論文]
  • Takuya Sho, Goki Suda, Atsushi Nagasaka, Yoshiya Yamamoto, Ken Furuya, Kenichi Kumagai, Minoru Uebayashi, Katsumi Terashita, Tomoe Kobayashi, Izumi Tsunematsu, Manabu Onodera, Takashi Meguro, Megumi Kimura, Jun Ito, Machiko Umemura, Takaaki Izumi, Naoki Kawagishi, Masatsugu Ohara, Yuji Ono, Masato Nakai, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 48 7 529 - 538 2018年06月 [査読有り][通常論文]
     
    AIM: The safety and efficacy of sofosbuvir (SOF) and ribavirin (RBV) have not been well clarified in patients with renal dysfunction because clinical trials have not included such patients. We evaluated the safety and efficacy of SOF and RBV for genotype 2 hepatitis C virus (HCV)-infected patients with renal dysfunction. METHODS: The study included genotype 2 HCV-infected patients who received SOF and RBV between July 2014 and May 2017. The sustained virologic response (SVR) after the treatment and safety during the therapy were evaluated according to renal function. RESULTS: A total of 231 patients were included in this study. The median age was 62 years old, and 45.9% (106/231) were men. Of the 231 patients, 191 (82.8%) and 40 (17.2%) were classified as having chronic kidney disease (CKD) stages G1/2 and G3, respectively. The overall SVR rate was 97% (224/231). The SVR rates in patients with CKD stages G1, 2, G3a, and G3b were 98.1%, 98.6%, 87.9%, and 100%, respectively, and this therapy was tolerated. Multivariate analysis indicated that renal dysfunction was significantly associated with a non-SVR (odds ratio, 6.963; 95% confidence interval, 1.494-32.41; P = 0.013). The patients with renal dysfunction were older, had advanced liver fibrosis, lower baseline platelet and hemoglobin levels, and a higher rate of RBV dose reduction. CONCLUSIONS: Sofosbuvir and RBV therapy is highly effective and safe for genotype 2 HCV-infected Japanese patients. However, attention should be paid to baseline renal function when SOF- and RBV-containing regimens are used for patients with renal dysfunction.
  • Hiromi Sawai, Nao Nishida, Seik-Soon Khor, Masao Honda, Masaya Sugiyama, Natsumi Baba, Kayoko Yamada, Norie Sawada, Shoichiro Tsugane, Kazuhiko Koike, Yuji Kondo, Hiroshi Yatsuhashi, Shinya Nagaoka, Akinobu Taketomi, Moto Fukai, Masayuki Kurosaki, Namiki Izumi, Jong-Hon Kang, Kazumoto Murata, Keisuke Hino, Sohji Nishina, Akihiro Matsumoto, Eiji Tanaka, Naoya Sakamoto, Koji Ogawa, Kazuhide Yamamoto, Akihiro Tamori, Osamu Yokosuka, Tatsuo Kanda, Isao Sakaida, Yoshito Itoh, Yuichiro Eguchi, Satoshi Oeda, Satoshi Mochida, Man-Fung Yuen, Wai-Kay Seto, Yong Poovorawan, Nawarat Posuwan, Masashi Mizokami, Katsushi Tokunaga
    Scientific reports 8 1 7958 - 7958 2018年05月21日 [査読有り][通常論文]
     
    We have performed a genome-wide association study (GWAS) including 473 Japanese HBV (hepatitis B virus)-positive HCC (hepatocellular carcinoma) patients and 516 HBV carriers including chronic hepatitis and asymptomatic carrier individuals to identify new host genetic factors associated with HBV-derived HCC in Japanese and other East Asian populations. We identified 65 SNPs with P values < 10-4 located within the HLA class I region and three SNPs were genotyped in three independent population-based replication sets. Meta-analysis confirmed the association of the three SNPs (rs2523961: OR = 1.73, P = 7.50 × 10-12; rs1110446: OR = 1.79, P = 1.66 × 10-13; and rs3094137: OR = 1.73, P = 7.09 × 10-9). We then performed two-field HLA genotype imputation for six HLA loci using genotyping data to investigate the association between HLA alleles and HCC. HLA allele association testing revealed that HLA-A * 33:03 (OR = 1.97, P = 4.58 × 10-4) was significantly associated with disease progression to HCC. Conditioning analysis of each of the three SNPs on the HLA class I region abolished the association of HLA-A*33:03 with disease progression to HCC. However, conditioning the HLA allele could not eliminate the association of the three SNPs, suggesting that additional genetic factors may exist in the HLA class I region.
  • Goki Suda, Koji Ogawa, Kenichi Morikawa, Naoya Sakamoto
    Journal of gastroenterology 53 5 591 - 605 2018年05月 [査読有り][通常論文]
     
    Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis and hepatocellular carcinoma. In hemodialysis patients, the rate of HCV infection is high and is moreover associated with a poor prognosis. In liver transplantation patients with HCV infection, recurrent HCV infection is universal, and re-infected HCV causes rapid progression of liver fibrosis and graft loss. Additionally, in patients with HCV and human immunodeficiency virus (HIV) co-infection, liver fibrosis progresses rapidly. Thus, there is an acute need for prompt treatment of HCV infection in these special populations (i.e., hemodialysis, liver transplantation, HIV co-infection). However, until recently, the standard anti-HCV treatment involved the use of interferon-based therapy. In these special populations, interferon-based therapies could not achieve a high rate of sustained viral response and moreover were associated with a higher rate of adverse events. With the development of novel direct-acting antivirals (DAAs), the landscape of anti-HCV therapy for special populations has changed dramatically. Indeed, in special populations treated with interferon-free DAAs, the sustained viral response rate was above 90%, with a lower incidence and severity of adverse events.
  • Goki Suda, Jun Ito, Atsushi Nagasaka, Yoshiya Yamamoto, Ken Furuya, Munenori Okamoto, Katsumi Terashita, Tomoe Kobayashi, Izumi Tsunematsu, Junichi Yoshida, Takashi Meguro, Masatsugu Ohara, Naoki Kawagishi, Megumi Kimura, Machiko Umemura, Takaaki Izumi, Yoko Tsukuda, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 48 3 E146-E154  2018年02月 [査読有り][通常論文]
     
    BACKGROUND: The Japan Society of Hepatology guidelines indicate that hepatitis C virus (HCV) protease inhibitor combination therapy with simeprevir (SMV), pegylated-interferon (Peg-IFN), and ribavirin (RBV) is a therapeutic option for patients who fail to respond to a direct direct-acting antiviral-containing regimen. However, treatment outcomes have room for improvement. Fluvastatin (FLV) add-on treatment in Peg-IFN and RBV combination therapy for HCV-infected patients significantly improved the sustained virologic response (SVR), but the add-on effect of FLV on SMV combination therapy is not well understood. METHODS: This was a prospective, randomized, multicenter study in which a total of 61 HCV genotype 1b-infected patients were recruited and 60 eligible patients were randomly allocated to two groups that received 12 weeks of SMV/Peg-IFN/RBV followed by 12 weeks of Peg-IFN/RBV with or without 24 weeks of FLV. The SVR rate and adverse events were compared between the two groups. RESULTS: Thirty-one patients were allocated to the FLV add-on group and 29 patients were allocated to the control group. Baseline clinical factors, including median age, baseline platelet count, alanine aminotransferase level, HCV RNA titer, Fibrosis-4 index, and rate of IL28B minor genotype, were all similar between the two groups. The rapid virologic response, end-of-treatment response rates, SVR rates at 24 weeks after treatment, and safety profiles were also similar between the two groups. CONCLUSIONS: This prospective, randomized, multicenter study indicated that FLV had no add-on effect when given with SMV/Peg-IFN/RBV combination therapy for genotype 1b HCV-infected patients.
  • Masato Nakai, Koji Ogawa, Rei Takeda, Masatsugu Ohara, Naoki Kawagishi, Takaaki Izumi, Machiko Umemura, Jun Ito, Takuya Sho, Goki Suda, Kenichi Morikawa, Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 48 3 E311-E319  2018年02月 [査読有り][通常論文]
     
    AIM: Water retention, hepatic ascites, and peripheral edema are significant problems in patients with liver cirrhosis (LC). Although furosemide and spironolactone are commonly used as treatment, they are often insufficient to treat hyponatremia and renal insufficiency in patients with LC. Tolvaptan (TVP) could provide an effective treatment alternative. However, predictive factors of a therapeutic response to TVP are unclear. Our aim was to examine clinical predictors of the response to TVP in patients with LC and water retention. METHODS: Fifty-two patients were treated with TVP, with therapeutic effects judged by a decrease in body weight (≥2 kg) and increase in urinary volume (≥500 mL) within 7 days. Blood biochemical tests were carried out at baseline and post-treatment, including serum soluble CD14 (sCD14) and urinary aquaporin 2 (AQP2) levels. Clinical and laboratory predictive factors of a TVP response were evaluated by univariate and multivariate analyses. RESULTS: The overall response to TVP was 55.8%. On univariate analyses, serum C-reactive protein (CRP) level, the neutrophil-to-lymphocyte ratio, urinary blood urea nitrogen, and urinary AQP2 were predictors of the TVP response, with only serum CRP retained on multivariate analysis. A higher serum sCD14 level was strongly associated with a non-response to TVP. A decrease in urinary AQP2 to undetectable level was associated with a response. CONCLUSION: Tolvaptan provides a rapid and strong effect to improve water retention in patients with LC. Baseline serum sCD14 and CRP levels are useful predictors of a response to TVP, with a decrease in urinary AQP2 during treatment indicating an early response.
  • Kawagishi N, Suda G, Nakamura A, Kimura M, Maehara O, Suzuki K, Nakamura A, Ohara M, Izumi T, Umemura M, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Kudo Y, Nishida M, Miyoshi H, Sakamoto N
    PloS one 13 12 e0209615 - e0209615 2018年 [査読有り][通常論文]
  • Goki Suda, Norihiro Furusyo, Hidenori Toyoda, Yoshiiku Kawakami, Hiroki Ikeda, Michihiro Suzuki, Keiko Arataki, Nami Mori, Keiji Tsuji, Yoshio Katamura, Koichi Takaguchi, Toru Ishikawa, Kunihiko Tsuji, Noritomo Shimada, Atsushi Hiraoka, Sho Yamsaki, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Mineo Kudo, Atsushi Nagasaka, Ken Furuya, Yoshiya Yamamoto, Kanji Kato, Yoshiyuki Ueno, Etsuko Iio, Yasuhito Tanaka, Masayuki Kurosaki, Takashi Kumada, Kazuaki Chayama, Naoya Sakamoto
    Journal of gastroenterology 53 1 119 - 128 2018年01月 [査読有り][通常論文]
     
    BACKGROUND: Hepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV). METHODS: Twenty-three centers in Japan participated in this study of 123 hemodialysis patients with genotype 1 HCV infection, who received DCV/ASV combination therapy between November 2014 and March 2016. We collected and analyzed data relating to treatment outcome, baseline clinical information, laboratory measurements (during and after the treatment), and adverse events. RESULTS: Thirty-nine patients (31.7%) had advanced liver fibrosis, 12 (9.8%) had histories of hepatocellular carcinoma (HCC), and 18 (14.6%) had baseline resistance-associated variants (RAVs) of NS5A. The overall sustained virological response (SVR)12 rate was 95.9% (118/123). Notably, all patients with HCC and 94.4% (17/18) of those with NS5A RAVs achieved SVR12. Significant factors associated with non-SVR were advanced fibrosis and the interleukin-28B non-TT genotype at rs8099917. Four patients (3.3%) discontinued therapy because of adverse events including elevated serum alanine transaminase levels (n = 2), rash (n = 1), and HCC (n = 1); all of these achieved SVR12. CONCLUSIONS: This real-world, nationwide study revealed that DCV/ASV combination therapy was safe and highly effective for hemodialysis patients with genotype 1 HCV infections. This study was registered at the UMIN Clinical Trials Registry (UMIN000024227).
  • Naoki Kawagishi, Goki Suda, Masahiro Onozawa, Megumi Kimura, Osamu Maehara, Jun Ito, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    JOURNAL OF HEPATOLOGY 67 5 1106 - 1108 2017年11月 [査読有り][通常論文]
  • Osamu Maehara, Goki Suda, Mitsuteru Natsuizaka, Shunsuke Ohnishi, Yoshito Komatsu, Fumiyuki Sato, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Tomoe Shimazaki, Megumi Kimura, Ayaka Asano, Yoshiyuki Fujimoto, Shinya Ohashi, Shingo Kagawa, Hideaki Kinugasa, Seiji Naganuma, Kelly A. Whelan, Hiroshi Nakagawa, Koji Nakagawa, Hiroshi Takeda, Naoya Sakamoto
    CARCINOGENESIS 38 11 1073 - 1083 2017年11月 [査読有り][通常論文]
     
    In esophageal squamous cell carcinoma (ESCC), a subset of cells defined by high expression of CD44 and low expression of CD24 has been reported to possess characteristics of cancer stem-like cells (CSCs). Novel therapies directly targeting CSCs have the potential to improve prognosis of ESCC patients. Although fibroblast growth factor-2 (FGF-2) expression correlates with recurrence and poor survival in ESCC patients, the role of FGF-2 in regulation of ESCC CSCs has yet to be elucidated. We report that FGF-2 is significantly upregulated in CSCs and significantly increases CSC content in ESCC cell lines by inducing epithelial-mesenchymal transition (EMT). Conversely, the FGFR inhibitor, AZD4547, sharply diminishes CSCs via induction of mesenchym al-epithelial transition. Further experiments revealed that MAPK/Erk kinase (Mek)/extracellular signal-regulated kinases (Erk) pathway is crucial for FGF-2-mediated CSC regulation. Pharmacological inhibition of FGF receptor (FGFR)-mediated signaling via AZD4547 did not affect CSCs in Ras mutated cells, implying that Mek/Erk pathway, downstream of FGFR signaling, might be an important regulator of CSCs. Indeed, the Mek inhibitor, trametinib, efficiently suppressed ESCC CSCs even in the context of Ras mutation. Consistent with these findings in vitro, xenotransplantation studies demonstrated that inhibition of FGF-2-mediated FGFR/Erk signaling significantly delayed tumor growth. Taken together, these findings indicate that FGF-2 is an essential factor regulating CSCs via Mek/Erk signaling in ESCC. Additionally, inhibition of FGFR and/or Mek signaling represents a potential novel therapeutic option for targeting CSCs in ESCC.
  • Goki Suda, Atsushi Nagasaka, Yoshiya Yamamoto, Ken Furuya, Kenichi Kumagai, Mineo Kudo, Katsumi Terashita, Tomoe Kobayashi, Izumi Tsunematsu, Junichi Yoshida, Takashi Meguro, Megumi Kimura, Jun Ito, Machiko Umemura, Takaaki Izumi, Seiji Tsunematsu, Fumiyuki Sato, Yoko Tsukuda, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    HEPATOLOGY RESEARCH 47 11 1127 - 1136 2017年10月 [査読有り][通常論文]
     
    Aim: Hepatitis C virus (HCV) infection is a risk factor for end-stage renal disease, renal graft failure, and hemodialysis patient mortality. However, the efficacy of direct-acting antiviral therapy for HCV-infected patients with renal impairment is unclear. Additionally, the promising NS5B inhibitor sofosbuvir has not been recommended for patients with severe renal impairment. In this prospective, multicenter study, we evaluated the efficacy and safety of daclatasvir and asunaprevir combination therapy, with a focus on patients with renal impairment.Methods: The study included 322 genotype 1 HCV-infected patients who received daclatasvir and asunaprevir combination therapy. The safety and sustained virological response was examined at 12weeks after the end of treatment and safety was evaluated according to renal function.Results: Of 322 patients, 5% (16/322) and 2.5% (8/322) had chronic kidney disease stage G3b (estimated glomerular filtration rate [eGFR], 30-44mL/min/1.73m(2)) and stage G4/5 (eGFR, 15-29/<15mL/min/1.73m(2)), respectively. Baseline presence of the NS5A resistance-associated variant, previous simeprevir treatment, and HCV RNA titers, which were predictors of a sustained viral response, were similar between patients with eGFR <45mL/min/1.73m(2) and eGFR >45mL/min/1.73m(2). Notably, the 12-week sustained viral response rate was comparable in patients with eGFR <45mL/min/1.73m(2) (100%, 24/24) and those with eGFR >45mL/min/1.73m(2) (88.9%, 265/298; P=0.07). Treatment discontinuation rates and adverse events, including alanine aminotransferase elevation, anemia, and renal disorders, were similar between the two groups.Conclusion: Daclatasvir and asunaprevir combination therapy for patients with renal dysfunction was highly effective and safe.
  • Goki Suda, Koji Ogawa, Yoshiya Yamamoto, Masaki Katagiri, Ken Furuya, Kenichi Kumagai, Jun Konno, Megumi Kimura, Naoki Kawagishi, Masatsugu Ohara, Machiko Umemura, Jun Ito, Takaaki Izumi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Akihito Tsubota, Noritomo Shimada, Etsuko Iio, Yasuhito Tanaka, Naoya Sakamoto
    JOURNAL OF GASTROENTEROLOGY 52 10 1122 - 1129 2017年10月 [査読有り][通常論文]
     
    Background The optimal retreatment regimen for patients with hepatitis C virus (HCV) infection who failed interferon-free, direct-acting antiviral (DAA) therapy is undetermined. In this study, we aimed to evaluate the efficacy and safety of 12-week retreatment with ledipasvir (LDV) and sofosbuvir (SOF) with add-on ribavirin (RBV) for patients who previously failed to respond to HCV-NS5A inhibitor, daclatasvir (DCV), and HCV-NS3 inhibitor, asunaprevir (ASV), therapy.Methods This multicenter, prospective study enrolled 15 patients with genotype-1 HCV infection who failed DCV/ASV combination therapy. They were retreated with SOF, LDV, and RBV for 12 weeks and underwent physical examinations and blood tests at baseline, during treatment, and after therapy. At baseline and relapse, NS3/NS5A and NS5B resistance-associated variants (RAVs) were evaluated.Results Of the 15 enrolled patients, 73.3% (11/15), 86.7% (13/15), and 0% (0/15) had RAVs in NS3 D168A/V/T/E, NS5A L31I/M/F/V plus Y93H, and NS5B S282T, respectively. Overall, 86.7%(13/15) of patients achieved a sustained viral response, and all patients completed therapy. No patients experienced severe adverse events. Two patients who failed to respond to SOF, LDV, and RBV combination therapy were elderly women, had the IL28B non-TT genotype, and NS5A RAVs in L31I/Y93H or NS5A A92 K at baseline.Conclusions This study revealed that SOF, LDV, and RBV combination therapy was effective and well-tolerated for patients with genotype-1 HCV infection who failed DCV and ASV combination therapy. Thus, RBV added to DAA therapy for difficult-to-treat patients might improve treatment outcomes.
  • Takuya Sho, Mitsuru Nakanishi, Kenichi Morikawa, Masatsugu Ohara, Naoki Kawagishi, Takaaki Izumi, Machiko Umemura, Jun Ito, Masato Nakai, Goki Suda, Koji Ogawa, Makoto Chuma, Takashi Meguro, Michio Nakamura, Atsushi Nagasaka, Hiromasa Horimoto, Yoshiya Yamamoto, Naoya Sakamoto
    Drugs in R&D 17 3 381 - 388 2017年09月 [査読有り][通常論文]
     
    BACKGROUND AND AIMS: Sorafenib is the first molecular targeted drug approved for the treatment of advanced hepatocellular carcinoma (HCC) and is a potent small molecule inhibitor of multiple kinases. Combination therapy with sorafenib and other cytotoxic agents for HCC may result in additive anticancer activity. The purpose of this phase I study was to investigate the safety and tolerability of combination therapy with sorafenib and 5-fluorouracil (5-FU) and to determine the optimum dose of 5-FU for a phase II trial. METHODS: This phase I study used a conventional 3 + 3 dose-escalation design. The primary endpoint was to determine the maximum tolerated dose (MTD) of 5-FU in combination with sorafenib and to determine the recommended dosage (RD) for phase II. The secondary endpoints evaluated were toxicity and the tumor response rate. All patients received 800 mg of sorafenib daily and three different dosages of 5-FU (250, 350, and 450 mg/m2/day) for 20 days by intravenous infusion in 1 month as one cycle. RESULTS: Twelve patients with advanced HCC were evaluated. The MTD of 5-FU in combination with sorafenib was 450 mg/m2/day, and 350 mg/m2/day was selected as the RD for a phase II study. Thrombocytopenia, stomatitis, and hand-foot skin reaction were observed as grade 3 adverse events. Nine patients achieved stable disease (75%), and three patients (25%) were judged to have progressive disease. The disease control rate was 75%. CONCLUSIONS: Combination therapy with sorafenib and 5-FU appears to be well tolerated and may have the potential to be an option for advanced HCC.
  • Tsunematsu S, Suda G, Yamasaki K, Kimura M, Takaaki I, Umemura M, Ito J, Sato F, Nakai M, Sho T, Morikawa K, Ogawa K, Kamiyama T, Taketomi A, Sakamoto N
    Hepatology research : the official journal of the Japan Society of Hepatology 47 6 533 - 541 2017年05月 [査読有り][通常論文]
     
    AimHepatic arterial infusion chemotherapy (HAIC) is a potent therapeutic option for advanced hepatocellular carcinoma (HCC). However, there are few known predictive factors of treatment response to HAIC. We clarified the most accurate predictive factors early on in treatment.MethodsStudy subjects were 70 patients with advanced HCC who had been treated with HAIC. We assessed the relationships between patient characteristics, change ratios of early tumor markers, tumor response, progression-free survival (PFS), and overall survival.ResultsAfter two courses of HAIC, 1 (1.4%), 16 (22.9%), 30 (42.8%), and 23 (32.9%) of the 70 patients showed complete response, partial response, stable disease, and progressive disease, respectively. Overall survival was related to Child-Turcotte-Pugh score, extrahepatic metastasis, and the des--carboxyprothrombin (DCP) response. Univariate and multivariate analyses identified the neutrophil-to-lymphocyte ratio (NLR) and DCP response as significant determinants of treatment response and PFS. Progression-free survival with a low NLR (<2.87) was significantly longer than with a high NLR (median, 8.4months vs. 2.8months, respectively). Progression-free survival was 7.2months for patients with a responsive DCP (<0.7) and 2.3months for an unresponsive DCP (0.7). Additionally, even with baseline high NLR, patients with responsive DCP achieved better PFS.ConclusionBaseline NLR and early DCP response were significant predictors of treatment response and PFS after HAIC for patients with advanced HCC. The combination of baseline NLR and early DCP response could be accurate and useful predictive factors of response to HAIC and could help optimize treatments for patients with advanced HCC.
  • Yoko Tsukuda, Goki Suda, Seiji Tsunematsu, Jun Ito, Fumiyuki Sato, Katsumi Terashita, Masato Nakai, Takuya Sho, Osamu Maehara, Tomoe Shimazaki, Megumi Kimura, Kenichi Morikawa, Mitsuteru Natsuizaka, Koji Ogawa, Shunsuke Ohnishi, Makoto Chuma, Naoya Sakamoto
    JOURNAL OF MEDICAL VIROLOGY 89 5 857 - 866 2017年05月 [査読有り][通常論文]
     
    Hepatitis C virus (HCV) has been reported to hijack fatty acid metabolism in infected hepatocytes, taking advantage of lipid droplets for virus assembly. In this study, we analyzed the anti-HCV activity of L-carnitine, a substance involved in the transport of fatty acids into mitochondria. JFH-1 or HCV replicontransfected Huh7.5.1 cells were treated with or without L-carnitine to examine its anti-HCV effects. The effects of L-carnitine on HCV entry, HCV-induced adipogenesis and lipid droplet formation, and HCV-induced oxidative stress were examined. Treatment of JFH1-infected cells with L-carnitine inhibited HCV propagation in a concentration-dependent manner. In contrast, L-carnitine had no antiHCV activity in the HCV replicon system, which is lacking viral assembly. In addition, Lcarnitine did not affect HCV entry. However, Lcarnitine treatment decreased intracellular lipid droplets, which are crucial for HCV assembly in JFH-1-infected cells. The expression level of CPT-1 was decreased in JFH-1-infected cells, and L-carnitine treatment restored this expression. HCV-infected cells exhibited increased production of reactive oxygen species and glutathione oxidation. L-carnitine decreased oxidative stress induced by JFH-1-infection, as shown by glutathione/glutathione disulfide assays and MitoSOX staining. L-carnitine exhibited anti-HCV activity, possibly by inhibiting HCV assembly and through its anti-adipogenic activity in HCV-infected cells. Moreover, L-carnitine has antioxidant properties in HCVinfected hepatocytes. Overall, these results indicated that L-carnitine may be an effective adjunctive agent in antiviral therapies to treat chronic hepatitis C. (C) 2016 Wiley Periodicals, Inc.
  • Tsunematsu S, Suda G, Yamasaki K, Kimura M, Izumi T, Umemura M, Ito J, Sato F, Nakai M, Sho T, Morikawa K, Ogawa K, Tanaka Y, Watashi K, Wakita T, Sakamoto N
    Journal of medical virology 89 2 267 - 275 2017年02月 [査読有り][通常論文]
     
    Hepatitis B Virus (HBV) causes liver cirrhosis and hepatocellular carcinoma. Standard therapy includes treatment with interferon (IFN); however, its efficacy is limited. HBV has been reported to impair IFN signaling; however, the mechanism is unclear. Here, the relationship between HBV X protein (HBx) and IFN signaling was investigated by establishing HepG2 cells, stably expressing HBx (HepG2/HBx) via retrovirus-mediated gene transfer. Subsequently, IFN negative-regulator expression and its mechanism were studied. HepG2/HBx cells showed reduced expression of IFN-stimulated genes and expressed higher levels of suppressor of cytokine signaling 3 (SOCS3) and protein phosphatase 2A (PP2A) suppressor compared with control cells. Knockdown of SOCS3 and PP2A restored IFN sensitivity. Moreover, HepG2/HBx cells showed higher phosphorylation levels of signal transducers and activators of transcription 3 and endoplasmic reticulum stress, which are inducers of SOCS3 and PP2A, respectively. Additionally, HBx-knockdown restored IFN sensitivity in HepG2.2.15.7 cells. It was also confirmed that SOCS3 and PP2A expression levels were up-regulated in the liver of patients with HBV infection. The results of this study demonstrated that HBx impairs IFN signaling via increased expression of SOCS3 and PP2A, a novel mechanistic insight, providing a potential therapeutic target to enhance the efficiency of IFN therapy. J. Med. Virol. 89:267-275, 2017. (c) 2016 Wiley Periodicals, Inc.
  • 中井 正人, 森川 賢一, 大原 正嗣, 川岸 直樹, 出水 孝章, 梅村 真知子, 伊藤 淳, 常松 聖司, 佐藤 史幸, 荘 拓也, 須田 剛生, 小川 浩司, 坂本 直哉
    日本消化器病学会雑誌 114 5 839 - 845 一般財団法人 日本消化器病学会 2017年 
    ウイルソン病は原因不明の肝機能障害，肝硬変における鑑別診断の1つである．多くは幼少期に診断されるが，成人後に肝硬変として発見される症例も経験する．血清セルロプラスミン，尿中銅などの測定にて診断可能な症例もあるが，診断に苦慮し，ATP7B遺伝子変異検査や肝組織中銅含有量測定が必要な場合もある．米国肝臓病学会，ヨーロッパ肝臓学会から診断ガイドラインが提唱されており，本邦でも2015年にウイルソン病診断ガイドラインが発表され，診断困難例においても，各ガイドラインに従った診断が可能となった．当科でのウイルソン病症例を各ガイドラインの診断基準，フローチャートを用いて検討し，その有用性を報告する．
  • Goki Suda, Koji Ogawa, Megumi Kimura, Masato Nakai, Takuya Sho, Kenichi Morikawa, Naoya Sakamoto
    Journal of clinical and translational hepatology 4 4 320 - 327 2016年12月28日 [査読有り][通常論文]
     
    Prevalence of hepatitis C virus (HCV) infection is high in patients with end-stage renal dysfunction, including patients undergoing hemodialysis (HD). The HCV infection itself can cause glomerulonephritis and puts individuals at increased risk of developing end-stage renal disease; fortunately, successful HCV eradication sometimes restore HCV-related renal dysfunction. Moreover, the prognosis of dialysis patients infected with HCV is significantly worse and the renal allograft survival in HCV-infected patients is also worse than in dialysis patients without HCV infection. If life prognosis is favorable, therefore, anti-HCV therapy is strongly recommended for HCV-infected patients with severe renal dysfunction. The standard therapy for HCV-infected patients with severe renal dysfunction has historically been interferon-based therapy. However, this therapy remains ineffective in achieving high, sustained viral response rates and the rate of adverse events and treatment discontinuation due to treatment-induced adverse events continues to be high in patients with severe renal dysfunction. Safe and effective anti-HCV therapies are urgently needed, and crucial, for patients with severe renal dysfunction. Recently, direct-acting antivirals (DAAs) that specifically target viral proteins have been developed, and these targets include the NS3, NS5A, and NS5B of HCV. Clinical trials have revealed high efficacy and safety of the DAA-based therapies, but patients with severe renal dysfunction were not included in the majority of these trials. However, several recent reports have shown high efficacy and safety for some regimens of DAA combination therapy for HCV-infected patients with severe renal dysfunction. In this review, we discuss novel treatments for HCV-infected patients with severe renal dysfunction and the pharmacokinetics of these drugs.
  • Jun Ito, Goki Suda, Yoshiya Yamamoto, Atsushi Nagasaka, Ken Furuya, Kenichi Kumagai, Hideaki Kikuchi, Takuto Miyagishima, Tomoe Kobayashi, Megumi Kimura, Kazushi Yamasaki, Machiko Umemura, Takaaki Izumi, Seiji Tsunematsu, Fumiyuki Sato, Yoko Tsukuda, Katsumi Terashita, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    HEPATOLOGY RESEARCH 46 13 1294 - 1303 2016年12月 [査読有り][通常論文]
     
    Aim: Sofosbuvir (SOF), a nucleotide analog pro-drug, targets hepatitis C virus (HCV) NS5B polymerase and shows potential for treating HCV infection, given its high efficacy and good barrier to resistance. However, in addition to the rare resistant-associated variant (RAV) of non-structural protein NS5B S282T, several new potential RAVs of SOF have been reported, especially related to HCV genotype 1b. However, the prevalence and characteristics of these RAVs have not been clarified.Methods: We analyzed the prevalence of variants in the NS3/NS5A/NS5B regions in 96 patients treated with simeprevir (SMV) combination therapy, and the prevalence of RAVs in patients showing treatment failure was determined by direct- or deep-sequencing methods. Associations between these potential RAVs and clinical factors were also analyzed.Results: Prevalence of NS5B RAV C316N was high (46.9%, 45/96), whereas that of NS5B L159F was relatively low (1.04%, 1/96); however, deep sequencing showed that 30.0% of patients with C316N also had NS5B RAV L159F. Additionally, there was no significant relationship between the existence of potential NS5B and NS5A or NS3 RAVs. However, the presence of NS5B C316N was significantly associated with an HCV core amino acid 91 substitution. No significant difference was detected between each RAV and sustained virological response in simeprevir combination therapy.Conclusion: We provide clear evidence of the high prevalence of two potential naturally occurring NS5B RAVs (C316N and L159F) in Japan. It may be important to pay particular attention to these new potential RAVs, especially when using SOF-based therapy in patients with RAVs due to previous direct-acting antiviral therapy failure.
  • 坂本 直哉, 須田 剛生, 小川 浩司, 森川 賢一
    臨床消化器内科 31 11 1475 - 1479 日本メディカルセンター 2016年09月20日
  • Katsumi Terashita, Makoto Chuma, Yutaka Hatanaka, Kanako Hatanaka, Tomoko Mitsuhashi, Hideki Yokoo, Takumi Ohmura, Hiroyuki Ishizu, Shunji Muraoka, Atsushi Nagasaka, Takahiro Tsuji, Yoshiya Yamamoto, Nobuaki Kurauchi, Norihiko Shimoyama, Hidenori Toyoda, Takashi Kumada, Yuji Kaneoka, Atsuyuki Maeda, Koji Ogawa, Mitsuteru Natsuizaka, Hirofumi Kamachi, Tatsuhiko Kakisaka, Toshiya Kamiyama, Akinobu Taketomi, Yoshihiro Matsuno, Naoya Sakamoto
    JOURNAL OF CLINICAL PATHOLOGY 69 7 593 - 599 2016年07月 [査読有り][通常論文]
     
    Background/Aim Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive malignant tumours, so the identification of molecular targets for ICC is an important issue. Zinc finger E-box binding homeobox 1 (ZEB1) is a key inducer of epithelial-mesenchymal transition (EMT). The aim of the present study was to clarify the clinical significance of ZEB1 in ICC and the associations between ZEB1 expression and EMT-related proteins. Methods We immunohistochemically examined the expression of EMT-related proteins, namely ZEB1, vimentin and E-cadherin, in ICC specimens from 102 patients. The clinicopathological and prognostic values of these markers were evaluated. Results ZEB1 and vimentin were expressed in 46.1% and 43.1% of tumours, respectively, and E-cadherin expression was lost in 44.1% of tumours. ZEB1 expression showed a significant inverse correlation with E-cadherin expression (p=0.004) and a positive correlation with vimentin expression (p=0.022). Altered expression of ZEB1 was associated with aggressive tumour characteristics, including advanced tumour stage (p=0.037), undifferentiated-type histology (p=0.017), lymph node metastasis (p=0.024) and portal vein invasion (p=0.037). Moreover, overall survival rates were significantly lower for patients with high ZEB1 expression than for patients with low ZEB1 expression (p=0.027). Kaplan-Meier analysis also identified E-cadherin expression (p=0.041) and vimentin expression (p=0.049) as prognostic indicators for overall survival. Conclusions ZEB1 expression is associated with tumour progression and poor prognosis in patients with ICC through positive correlations with vimentin and negative correlations with E-cadherin. ZEB1 expression is associated with a poor prognosis and might be an attractive target for the treatment of ICC.
  • Goki Suda, Mineo Kudo, Atsushi Nagasaka, Ken Furuya, Yoshiya Yamamoto, Tomoe Kobayashi, Keisuke Shinada, Miki Tateyama, Jun Konno, Yoko Tsukuda, Kazushi Yamasaki, Megumi Kimura, Machiko Umemura, Takaaki Izumi, Seiji Tsunematsu, Fumiyuki Sato, Katsumi Terashita, Masato Nakai, Hiromasa Horimoto, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    JOURNAL OF GASTROENTEROLOGY 51 7 733 - 740 2016年07月 [査読有り][通常論文]
     
    HCV infection in chronic hemodialysis patients is high, has a poor prognosis and high risk of renal graft failure, and requires nosocomial infection control measures. However, options of anti-HCV therapy in such patients are limited and unsatisfactory. In this study, we report effectiveness and safety of HCV-NS5A-inhibitor daclatasvir (DCV) and protease-inhibitor asunaprevir (ASV) combination therapy for hemodialysis patients with HCV infection.This study was registered at the UMIN Clinical Trials Registry as UMIN000016355. Thirty-four dialysis patients were treated with DCV/ASV combination therapy between January 2015 and November 2015. Of those, 21 patients who were followed more than 12 weeks after treatment ended were included. We evaluated the 12-week sustained virologic response (SVR12) and adverse events during treatment.Of the 21 patients, four had compensated liver cirrhosis and three had resistance-associated variant of NS5A (NS5A RAVs)-Y93H at baseline. Overall, total of 95.5 % (20/21) of the patients achieved SVR12. Of note, all patients with cirrhosis or NS5A RAVs achieved SVR12. One relapser patient at 4 weeks post-treatment had NS3 D168E RAVs at baseline. A total of 20 patients (95.5 %) completed the 24-week therapy. One patient discontinued treatment at week 12 due to ALT elevations and achieved SVR12.DAV and ASV combination therapy for chronic hemodialysis patients with HCV infection was highly effective and well tolerated, even in elderly patients and patients with liver cirrhosis and NS5A-RAVs.
  • Nakai Masato, Itoh Jun, Sato Fumiyuki, Tsunematsu Seiji, Sho Takuya, Suda Goki, Morikawa Kenichi, Ogawa Koji, Sakamoto Naoya
    HEPATOLOGY 62 358A  2015年10月 [査読有り][通常論文]
  • Suda Goki, Tsunematsu Seiji, Nakai Masato, Itoh Jun, Natsuizaka Mitsuteru, Morikawa Kenichi, Ogawa Koji, Sakamoto Naoya
    HEPATOLOGY 62 1157A  2015年10月 [査読有り][通常論文]
  • Maehara O, Sato F, Natsuizaka M, Asano A, Kubota Y, Itoh J, Tsunematsu S, Terashita K, Tsukuda Y, Nakai M, Sho T, Suda G, Morikawa K, Ogawa K, Chuma M, Nakagawa K, Ohnishi S, Komatsu Y, Whelan KA, Nakagawa H, Takeda H, Sakamoto N
    Cancer biology & therapy 16 10 1453 - 1461 2015年10月 [査読有り][通常論文]
     
    In hepatocellular carcinoma (HCC), there exists a highly tumorigenic subset of cells defined by high expression of CD44 and CD133 that has been reported to contain cancer stem-like cells (CSCs). Kruppel-like factor 5 (KLF5) regulates many factors involved in cell cycle, migration, inflammation, angiogenesis and stemness and has cancer-promoting effects in some cancers. While some reports have indicated that KLF5 may have important roles in regulation of CSCs, what role, if any, KLF5 plays in regulation of CSCs in HCC remains to be elucidated. Flow cytometric analysis of CD44 and CD133 in HCC cell lines revealed subpopulations of CD44(High)/CD133(High) and CD44(Low)/CD133(Low) cells. We subsequently sorted these subpopulations and identified KLF5 as a gene that is significantly upregulated in CD44(High)/CD44(High) cells via RNA sequencing using next generation sequencing technology. Moreover, KLF5 overexpression enriched the CD44(High)/CD133(High) subpopulation and, consistent with the up-regulation of CD44(High)/CD133(High) cells, KLF5 overexpressing cells were more resistant to anti-cancer drugs and displayed enhanced colony-formation capacity. By contrast, knock-down of KLF5 by siRNA diminished the CD44(High)/CD133(High) subpopulation. When KLF5 was acetylated by TGF-1, the KLF5-mediated CD44(High)/CD133(High) subpopulation enrichment was abrogated. Oppositely, ectopic expression of an acetylation-deficient KLF5 mutant further increased CD44(High)/CD133(High) subpopulations as compared to cell expressing wild-type KLF5. These findings provide novel mechanistic insight into a pivotal role for KLF5 in the regulation of CSCs in HCC.
  • Suda G, Yamamoto Y, Nagasaka A, Furuya K, Kudo M, Chuganji Y, Tsukuda Y, Tsunematsu S, Sato F, Terasita K, Nakai M, Horimoto H, Sho T, Natsuizaka M, Ogawa K, Ohnishi S, Chuma M, Fujita Y, Abe R, Taniguchi M, Nakagawa M, Asahina Y, Sakamoto N, NORTE Study Group
    Hepatology research : the official journal of the Japan Society of Hepatology 45 8 837 - 845 2015年08月 [査読有り][通常論文]
     
    Aim: Telaprevir-based therapy for chronic hepatitis C patients is effective; however, the high prevalence of dermatological reactions is an outstanding issue. The mechanism and characteristics of such adverse reactions are unclear; moreover, predictive factors remain unknown. Granulysin was recently reported to be upregulated in the blisters of patients with Stevens-Johnson syndrome (SJS). Therefore, we investigated the risk factors for severe telaprevir-induced dermatological reactions as well as the association between serum granulysin levels and the severity of such reactions.Methods: A total of 89 patients who received telaprevir-based therapy and had complete clinical information were analyzed. We analyzed the associations between dermatological reactions and clinical factors. Next, we investigated the time-dependent changes in serum granulysin levels in five and 14 patients with grade 3 and non-grade 3 dermatological reactions, respectively.Results: Of the 89 patients, 57 patients had dermatological reactions, including nine patients with grade 3. Univariate analysis revealed that grade 3 dermatological reactions were significantly associated with male sex. Moreover, serum granulysin levels were significantly associated with the severity of dermatological reactions. Three patients with grade 3 dermatological reaction had severe systemic manifestations including SJS, drug-induced hypersensitivity syndrome, and systemic lymphoid swelling and high-grade fever; all were hospitalized. Importantly, among the three patients, two patients' serum granulysin levels exceeded 8ng/mL at onset and symptoms deteriorated within 6 days.Conclusion: Male patients are at high risk for severe telaprevir-induced dermatological reactions. Moreover, serum granulysin levels are significantly associated with the severity of dermatological reactions and may be a predictive factor in patients treated with telaprevir-based therapy.
  • Seiji Tsunematsu, Makoto Chuma, Toshiya Kamiyama, Noriyuki Miyamoto, Satoshi Yabusaki, Kanako Hatanaka, Tomoko Mitsuhashi, Hirofumi Kamachi, Hideki Yokoo, Tatsuhiko Kakisaka, Yousuke Tsuruga, Tatsuya Orimo, Kenji Wakayama, Jun Ito, Fumiyuki Sato, Katsumi Terashita, Masato Nakai, Yoko Tsukuda, Takuya Sho, Goki Suda, Kenichi Morikawa, Mitsuteru Natsuizaka, Mitsuru Nakanishi, Koji Ogawa, Akinobu Taketomi, Yoshihiro Matsuno, Naoya Sakamoto
    ABDOMINAL IMAGING 40 6 1492 - 1499 2015年08月 [査読有り][通常論文]
     
    Differentiating intrahepatic cholangiocarcinoma (ICC) from poorly differentiated hepatocellular carcinoma (p-HCC) is often difficult, but it is important for providing appropriate treatments. The purpose of this study was to examine the features differentiating ICC from p-HCC on contrast-enhanced dynamic-computed tomography (CT).This study examined 42 patients with pathologically confirmed ICC (n = 19) or p-HCC (n = 23) for which contrast-enhanced dynamic CT data were available. CT images were analyzed for enhancement patterns during the arterial phase, washout pattern, delayed enhancement, satellite nodules, capsular retraction, lesion shape, and presence of an intratumoral hepatic artery, intratumoral hepatic vein, intratumoral portal vein, and bile duct dilation around the tumor, portal vein tumor thrombus, lobar atrophy, or lymphadenopathy.Univariate analysis revealed the presence of rim enhancement (p = 0.037), lobulated shape (p = 0.004), intratumoral artery (p < 0.001), and bile duct dilation (p = 0.006) as parameters significantly favoring ICC, while a washout pattern significantly favored p-HCC (p < 0.001). Multivariate analysis revealed intratumoral artery as a significant, independent variable predictive of ICC (p = 0.037), and 15 ICCs (78.9%) showed this feature. Washout pattern was a significant, independent variable favoring p-HCC (p = 0.049), with 15 p-HCCs (65.2%) showing this feature.The presence of an intratumoral artery in the arterial phase on contrast-enhanced dynamic CT was a predictable finding for ICC, and the presence of a washout pattern was a predictable finding for p-HCC, differentiating between ICC and p-HCC.
  • Sato Fumiyuki, Natsuizaka Mitsuteru, Maehara Osamu, Asano Ayaka, Kubota Yoshimasa, Itoh Jun, Tsunematsu Seiji, Tsukuda Yoko, Terashita Katsumi, Nakai Masato, Sho Takuya, Suda Goki, Morikawa Kenichi, Ogawa Koji, Ohnishi Shunsuke, Sakamoto Naoya
    GASTROENTEROLOGY 148 4 S43  2015年04月 [査読有り][通常論文]
  • Kazuaki Harada, Kazuteru Hatanaka, Kenji Kinoshita, Yasuyuki Kawamoto, Hiroaki Yamato, Koji Ogawa, Yoshiya Yamamoto, Hirohito Naruse
    Japanese Journal of Cancer and Chemotherapy 41 7 897 - 900 2014年07月01日 [査読有り][通常論文]
     
    The prognosis for patients diagnosed with advanced colorectal cancer with liver metastases is poor. Chemotherapy should be administered with caution in such patients because of complications due to severe liver dysfunction. We report here the successful management of a case of advanced sigmoid colon cancer, with icterus due to severe liver metastases, treated with cetuximab as first-line therapy. A 72-year-old man presented at our institution with complaints of severe general fatigue, tarry stools, and abdominal distention. He was diagnosed with advanced sigmoid colon cancer with multiple liver metastases. Clinical examination revealed the presence of ascites. The patient had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 3. A biopsy specimen of the primary tumor showed well-moderately differentiated adenocarcinoma without KRAS mutation. He was diagnosed with advanced sigmoid colon cancer with multiple hepatic metastases. Cetuximab monotherapy was initiated as first-line treatment. After 4 courses of cetuximab monotherapy, results of laboratory tests showed an improvement, and a computed tomography (CT) scan revealed a regression in the size of the liver metastases. Because the results of liver function tests and the ECOG PS scores improved, we initiated combination chemotherapy with 5-fluorouracil, Leucovorin, oxaliplatin (FOLFOX), and cetuximab. This regimen was well tolerated up to 14 courses, during which the only adverse reaction reported was a rash of grade 2 toxicity. Thereafter, disease progression in the form of liver metastases resulted in a change in the combination therapy to irinotecan and S-1 (IRIS) as second-line chemotherapy. Thereafter, irinotecan and panitumumab were administered as third-line therapy. The patient continued chemotherapy on an outpatient basis however, he died due to disease progression 18 months after his first visit.
  • Nakai Masato, Seya Tsukasa, Matsumoto Misako, Aly Hussein H, Itoh Jun, Tsunematsu Seiji, Sato Fumiyuki, Tsukuda Yoko, Terashita Katsumi, Sho Takuya, Suda Goki, Natsuizaka Mitsuteru, Ogawa Koji, Sakamoto Naoya
    HEPATOLOGY 60 1083A - 1084A 2014年 [査読有り][通常論文]
  • Hiroaki Yamato, Hiroshi Kawakami, Kikuko Takagi, Koji Ogawa, Kazuteru Hatanaka, Yoshiya Yamamoto, Hirohito Naruse, Kazumichi Kawakubo, Naoya Sakamoto
    Gastrointestinal Endoscopy 79 4 676 - 678 2014年 [査読有り][通常論文]
  • Tomoe Kobayashi, Shuhei Hige, Katsumi Terashita, Masato Nakai, Hiromasa Horimoto, Takuya Sho, Mitsuru Nakanishi, Koji Ogawa, Makoto Chuma, Naoya Sakamoto, Masahiro Asaka
    JOURNAL OF GASTROENTEROLOGY 47 11 1228 - 1237 2012年11月 [査読有り][通常論文]
     
    An inosine triphosphatase (ITPA) single-nucleotide polymorphism (SNP) is associated with anemia induced by pegylated interferon and ribavirin (RBV) combination therapy in patients with chronic hepatitis C (CHC). However, there are very few reports on the hematological effects of RBV monotherapy. Here, hematological changes were monitored in patients with CHC who received RBV monotherapy, and the mechanism of these changes was investigated. Patients with CHC (n = 30) received RBV monotherapy for 4 weeks. The RBV dose was determined on the basis of body weight. Complete blood count, and serum erythropoietin (EPO) and thrombopoietin (TPO) levels were assessed. The associations between these parameters and the ITPA SNP (rs1127354) were analyzed. Over the 4 weeks, the median hemoglobin level of all patients decreased significantly, from 13.6 (10.5-16.6) to 11.7 (9.4-14.9) g/dl (P < 0.001), and the platelet counts increased, from 14.0 x 10(4) (8.9-37.4 x 10(4)) to 15.8 x 10(4) (10.2-40.6 x 10(4)) /mm(3) (P = 0.003). At week 4, hemoglobin levels differed between patients with the ITPA CC genotype and those with the AA or AC genotypes [11.1 (9.4-13.5) vs. 12.9 (12.5-14.9) g/dl, P = 0.001]. The platelet change ratio (i.e., platelet count at week 4/platelet count at baseline) in the patients with developing anemia was correlated with the increase in the serum EPO level over 4 weeks (r = 0.88, P = 0.002), but not with the increase in the serum TPO level over 4 weeks. RBV monotherapy induced anemia and affected thrombocytosis in patients with CHC. Elevated endogenous EPO may stimulate platelet production.
  • Makoto Chuma, Hiroshi Taguchi, Yoshiya Yamamoto, Shinichi Shimizu, Mitsuru Nakanishi, Koji Ogawa, Takuya Sho, Hiromasa Horimoto, Tomoe Kobayashi, Masato Nakai, Katsumi Terashita, Yusuke Sakuhara, Daisuke Abo, Yoko Tsukuda, Seiji Tsunematsu, Shuhei Hige, Mototsugu Kato, Hiroki Shirato, Masahiro Asaka
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 26 7 1123 - 1132 2011年07月 [査読有り][通常論文]
     
    Background and Aim: To evaluate the efficacy of intra-arterial 5-fluorouracil (5-FU) and subcutaneous interferon (IFN) combined with image-guided radiation therapy (IGRT) in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods: Twenty HCC patients with PVTT were treated with 5-FU and IFN combined with image-guided radiation therapy (IGRT) (IGRT group), and as controls, 20 patients with PVTT were treated with 5-FU and IFN alone (non-IGRT group). Overall survival (OS) time, response rates, time to progression (TTP) and safety were compared across groups. Results: Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) of PVTT were 5%, 55%, 40% and 0% in the IGRT group and 0%, 30%, 35% and 35%, in the non-IGRT group, respectively. CR, PR, SD, and PD of the whole tumor were 0%, 35%, 45% and 20% in the IGRT group and 0%, 30%, 35% and 35%, in the non-IGRT group, respectively. Overall median survival was significantly longer in the IGRT group (12.0 months 95% confidence interval [CI], 9.3-17.6 months) than in the non-IGRT group (9.1 months [95% Cl, 5.5-11.1 months]) (P = 0.041). TTP was significantly longer in the IGRT group (6.9 months [95% CI, 5.6-10.2 months]) than in the non-IGRT group (4.0 months [95% Cl, 3.3-6.4 months]) (P = 0.034). Conclusions: The response rates, median OS time and TTP in patients with advanced HCC with PVTT who received this novel combination therapy of intra-arterial 5-FU and subcutaneous IFN with TORT are encouraging, and this combination therapy warrants further investigation.
  • 小腸癌転移病巣にTS-1+CPT-11療法が奏効した1例
    畑中 一映, 林 秀幸, 中井 正人, 井上 弘行, 小川 浩司, 山本 文泰, 山本 義也, 片桐 雅樹, 成瀬 宏仁, 原 豊, 工藤 和洋, 高橋 一人
    函館医学誌 33 1 19 - 22 市立函館病院 2009年10月 [査読無し][通常論文]
     
    小腸癌術約1年後、腫瘍マーカーCA19-9の上昇、続いて肝S5、下大静脈周囲リンパ節、骨盤腔内に転移所見がみられた50歳代男性症例について検討した。術後補助化学療法としてテガフール・ウラシル(UFT)内服治療を行っていたが、抗癌剤感受性試験でテガフール・ギメラシル・オテラシルカリウム(TS-1)およびイリノテカン(CPT-11)が高感受性を示したことより、全身化学療法としてTS-1+CPT-11併用療法を開始した。経過中、Grade 1の脱毛、Grade 3の好中球数減少を認めたが他に重篤な有害事象はみられなかった。6コース(4週/コース)終了時点のCTで測定可能病変は消失し、PETでも集積を認めず、Complete response(CR)と判定した。小腸癌再発病変に対し、効果の高い治療法として選択肢の1つになりうる可能性が示された。
  • C型慢性肝炎に対するインターフェロン療法著効7年後に発症した細胆管癌成分に富む混合型肝癌の1例
    山本 義也, 林 秀幸, 中井 正人, 井上 弘行, 小川 浩司, 山本 文泰, 畑中 一映, 片桐 雅樹, 成瀬 宏仁, 吉田 淳, 鈴木 伸作, 倉内 宣明, 木村 純, 工藤 和洋, 下山 則彦
    函館医学誌 33 1 11 - 14 市立函館病院 2009年10月 [査読無し][通常論文]
     
    上腹部痛を主訴とするC型慢性肝炎の71歳男性について検討した。7年前インターフェロン(IFN)治療を受け、Sustained virological response(SVR)と判定されていた。腹部超音波検査、腹部造影CT検査、CTAP/CTHAで肝細胞癌と診断し、肝S6亜区域切除術を行った。腫瘍は25×25mm大で、褐色調で膨張性発育を呈する部分と白色調で硬い領域が存在した。肉眼上褐色調の領域はmid trabecular patternを示し、Edmondson II型の中分化型肝細胞癌で、Cytokeratin(CK)8/81、HEP-PAR1、CK7が陽性、CK19、粘液染色は陰性であった。白色調の領域はantler patternを示し、細胆管癌様で、CK8/81、CK7が陽性、HEP-PAR1、CK19、粘液染色は陰性であった。粘液産生を伴う典型的肝内胆管癌成分は認められないものの、肝細胞癌、胆管系の癌の両方が明瞭に区分されて存在し、混合型肝癌であった。
  • Koji Ogawa, Shuhei Hige, Mitsuru Nakanishi, Yoshiya Yamamoto, Makoto Chuma, Atsushi Nagasaka, Masahiro Asaka
    ANTIVIRAL THERAPY 14 4 513 - 522 2009年 [査読有り][通常論文]
     
    Background: We aimed to investigate the effects of ribavirin on hepatitis C virus (HCV). Immunological and virological effects were analysed in patients undergoing treatment with ribavirin monotherapy prior to the initiation of combination therapy with interferon-alpha. Methods: A total of 25 patients with chronic HCV infection were enrolled in this study. All patients received ribavirin for 4 weeks during monotherapy; subsequently, interferon-alpha 2b was additionally given as combined therapy. Patients were divided into two groups according to virological response. A rapid viral responder (RVR) was defined as a patient in whom HCV RNA became undetectable within 4 weeks after combination therapy. The changes of the T-helper (Th)1/Th2 subset of peripheral blood CD4(+) T-cells, serum cytokine levels and the alignment of the interferon sensitivity-determining region (ISDR) during ribavirin monotherapy were analysed by flow cytometry, ELISAs and sequencing methods. Results: A total of 17 patients were classed as RVR. In the RVR group, the mean SD serum alanine aminotransferase levels significantly decreased (before treatment 103 +/- 92 IU/I and after treatment 57 +/- 46 IU/I; P<0.05) during ribavirin monotherapy. The mean +/- SD Th1/Th2 ratio significantly increased (before treatment 13.9 +/- 5.1 and after treatment 16.7 +/- 6.2; P<0.05), but did not change in the non-RVR group. The levels of Th2 cytokines (interleukin-10 and soluble CD30) significantly decreased, especially in the RVR group. The mean +/- SD mutation rates of ISDR at the nucleotide level increased in the RVR group (before treatment 2.6 +/- 0.9 sites/clone and after treatment 3.9 +/- 1.6 sites/clone; P<0.05), but did not change in the non-RVR group. Conclusions: Ribavirin administration might increase the efficacy of interferon therapy for patients with chronic hepatitis C by stimulating the host immune system and promoting HCV gene mutation.
  • Makoto Chuma, Shuhei Hige, Mitsuru Nakanishi, Koji Ogawa, Mitsuteru Natsuizaka, Yoichi Yamamoto, Masahiro Asaka
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 23 9 1431 - 1436 2008年09月 [査読有り][通常論文]
     
    Background and Aim: Increased production of reactive oxygen species, which cause oxidative DNA damage, is considered to be related to hepatocarcinogenesis. 8-Hydroxy-2 '-deoxy-guanosine (8-OHdG) is a useful marker of DNA damage induced by oxidative stress. The aim of this study was to determine whether expression of 8-OHdG is a risk factor for the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection. Methods: The expression of 8-OHdG in liver biopsy specimens was assessed immunohistochemically. In total, 104 patients with chronic HCV infection who were diagnosed on liver biopsy between January 1987 and December 2002 were studied retrospectively. Univariate and multivariate analyses using age, gender, habitual drinking, tobacco exposure, diabetes mellitus, serum alanine aminotransferase level, HCV genotype, hepatic fibrosis, inflammation, steatosis, and 8-OHdG expression in liver biopsy specimens were conducted to identify factors related to the development of HCC. Results: On multivariate analysis, 8-OHdG and fibrosis were independent and significant risk factors for HCC development (relative risk, 2.48; P = 0.023; relative risk, 5.35; P = 0.001, respectively). Furthermore, the cumulative incidence rate of HCC in 39 patients with high 8-OHdG expression levels was significantly greater than that in 65 patients with low 8-OHdG expression levels (P = 0.043). In addition, liver 8-OHdG expression was correlated with hepatic inflammation. Conclusions: 8-OHdG is a risk factor for the development of HCC in patients with chronic HCV infection. Patients with chronic HCV who express 8-OHdG should be monitored carefully for the development of HCC.
  • Natsuizaka M, Hige S, Ono Y, Ogawa K, Nakanishi M, Chuma M, Yoshida S, Asaka M
    J Viral Hepat 12 2 154 - 159 2005年03月 [査読有り][通常論文]

その他活動・業績

  • 山田 錬, 森川 賢一, 中村 晃久, 出水 孝章, 梅村 真知子, 大原 正嗣, 中井 正人, 荘 拓也, 須田 剛生, 小川 浩司, 坂本 直哉 消化器・肝臓内科 = Gastroenterology & hepatology / 消化器・肝臓内科編集委員会 編 12 (2) 184 -192 2022年08月
  • 須田 剛生, 川岸 直樹, 大原 正嗣, 中井 正人, 荘 拓也, 小川 浩司, 坂本 直哉 消化器・肝臓内科 = Gastroenterology & hepatology / 消化器・肝臓内科編集委員会 編 12 (2) 172 -174 2022年08月
  • 須田 剛生, 小川 浩司, 坂本 直哉 消化器・肝臓内科 = Gastroenterology & hepatology / 消化器・肝臓内科編集委員会 編 11 (4) 489 -493 2022年04月
  • 山本 啓一朗, 後藤 了一, 深澤 拓夢, 巖築 慶一, 川村 典生, 渡辺 正明, 小川 浩司, 堀田 記世彦, 岩見 大基, 篠原 信雄, 嶋村 剛, 武冨 紹信 北海道外科雑誌 65 (2) 158 -163 2020年12月 [査読有り]
     
    今回、原発性胆汁性胆管炎による肝腎不全に対し脳死肝腎同時移植を施行したので報告する。症例は46歳女性。35歳頃、原発性胆汁性胆管炎と診断。43歳時に黄疸発症し、非代償性肝硬変(T-bil 7.4mg/dl、Child Turcotte Pugh(CTP)B9点、Model for End-stage Liver Disease(MELD)score 7点)で当院紹介。2年後に肝不全進行し(T-bil 15.9、CTP C12、MELD22)、脳死登録された。3ヵ月後、T-bil 21.1、CTP C12、MELD27と増悪し、肝腎症候群から透析導入となった。透析導入8週後に腎移植も脳死移植登録した。待機期間246日で脳死ドナー発生、肝腎同時移植を実施した。術後膵炎を認めたが、肝機能は良好に推移し、術後12日目で透析離脱、術後57日目で退院した。術後11ヵ月の時点で、経過良好で外来フォロー中である。今後、肝腎不全に陥った症例に対しても肝腎同時移植を施行することで長期予後改善の可能性が期待される。(著者抄録)
  • 小川 浩司, 鈴木 和治, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉 肝臓 60 (11) 397 -404 2019年11月 [査読有り][通常論文]
     
    PIVKA-IIは肝細胞癌に特異性の高い腫瘍マーカーとして知られ、診断の補助や治療効果の判定などに用いられている。今回CLIA法を測定原理としたアーキテクト・PIVKA-IIを用いて、臨床症例における有用性を検討した。慢性肝疾患患者168例(慢性肝炎29例、肝硬変28例、肝細胞癌stage1 29例、stage2 29例、stage3 26例、stage4 27例)を対象とした。保存血清からアーキテクト・PIVKA-IIを測定し、診療時に測定したルミパルスPIVKA-IIおよびAFP値と比較検討を行った。両試薬ともに、肝細胞癌のstage進行に伴って上昇し、AFPとの組み合わせによる診断精度も同等であった。両試薬の測定値は高い相関性を示した。アーキテクト・PIVKA-IIは臨床検体において従来試薬と同等の診断精度を有しており、実臨床でも有用と考えられた。(著者抄録)
  • 中井正人, 重沢拓, 鈴木和治, 中村晃久, 大原正嗣, 川岸直樹, 梅村真知子, 荘拓也, 須田剛生, 森川賢一, 小川浩司, 坂本直哉 肝臓 60 (Supplement 1) A523 -A523 2019年04月20日 [査読無し][通常論文]
  • B型肝炎の抗ウイルス療法:肝発癌の制御を目指した治療の最前線 B型慢性肝炎の核酸アナログ治療におけるインターフェロンλ3の役割の検討
    森川 賢一, 小川 浩司, 坂本 直哉 肝臓 60 (Suppl.1) A73 -A73 2019年04月 [査読無し][通常論文]
  • 【B型肝炎治療におけるアンメットニーズ】肝線維化を戻すことは可能か
    小川 浩司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉 Progress in Medicine 39 (4) 405 -408 2019年04月 [査読無し][通常論文]
  • 肝疾患患者における筋肉量測定方法別の経時的変化
    大原 正嗣, 重沢 拓, 中村 晃久, 鈴木 和治, 梅村 真知子, 川岸 直樹, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉 日本消化器病学会雑誌 116 (臨増総会) A372 -A372 2019年03月 [査読無し][通常論文]
  • 進行肝細胞癌に対するレンバチニブの4週/8週における治療効果と安全性の検討
    荘 拓也, 須田 剛生, 重沢 拓, 鈴木 和治, 中村 晃久, 大原 正嗣, 川岸 直樹, 梅村 真知子, 中井 正人, 森川 賢一, 小川 浩司, 坂本 直哉 日本消化器病学会雑誌 116 (臨増総会) A415 -A415 2019年03月 [査読無し][通常論文]
  • 荘拓也, 須田剛生, 鈴木和治, 中村晃久, 大原正嗣, 川岸直樹, 梅村真知子, 中井正人, 森川賢一, 小川浩司, 坂本直哉 Liver Cancer Journal 10 (Suppl.2) 55‐56 -56 2018年12月10日 [査読無し][通常論文]
  • 【急速に変貌する肝細胞癌の薬物療法2018 Update】 免疫チェックポイント阻害剤同士のコンビネーション治療 ソラフェニブvsアテゾリズマブ+ベバシズマブの第III相試験(IMbrave150試験)
    小川 浩司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉 肝・胆・膵 77 (2) 486 -490 2018年08月 [査読無し][通常論文]
  • 進行肝細胞癌に対するソラフェニブ治療不応例の検討
    中村 晃久, 小川 浩司, 鈴木 和治, 大原 正嗣, 川岸 直樹, 出水 孝章, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉 The Liver Cancer Journal (Suppl.1) 75 -76 2018年06月 [査読無し][通常論文]
  • 進行肝細胞癌に対するソラフェニブ治療不応例の検討
    中村 晃久, 小川 浩司, 鈴木 和治, 大原 正嗣, 川岸 直樹, 出水 孝章, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉 The Liver Cancer Journal (Suppl.1) 75 -76 2018年06月 [査読無し][通常論文]
  • 鈴木和治, 須田剛生, 中村晃久, 大原正嗣, 川岸直樹, 出水孝章, 梅村真知子, 中井正人, 荘拓也, 森川賢一, 小川浩司, 坂本直哉 肝臓 59 (Supplement 1) A486 -A486 2018年04月20日 [査読無し][通常論文]
  • 川岸直樹, 鈴木和治, 中村晃久, 大原正嗣, 梅村真知子, 出水孝章, 中井正人, 荘拓也, 須田剛生, 森川賢一, 小川浩司, 坂本直哉 肝臓 59 (Supplement 1) A387 -A387 2018年04月20日 [査読無し][通常論文]
  • B型肝炎 HBs抗原陰性化を目指した治療戦略 B型慢性肝疾患に対するエンテカビル、テノホビルによるHBs抗原低下作用
    小川 浩司, 森川 賢一, 坂本 直哉 肝臓 59 (Suppl.1) A111 -A111 2018年04月 [査読無し][通常論文]
  • 肝硬変の成因別実態 肝硬変症の成因別実態
    小川 浩司, 鈴木 和治, 中村 晃久, 川岸 直樹, 大原 正嗣, 梅村 真知子, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉 肝臓 59 (Suppl.1) A272 -A272 2018年04月 [査読無し][通常論文]
  • 中島 収, 岩井 孝仁, 西田 睦, 表原 里実, 薮崎 哲史, 小川 浩司, 岡村 圭祐, 平野 聡, 三橋 智子, 加畑 馨, 清水 力 超音波医学 45 (1) 77 -79 2018年01月 [査読無し][通常論文]
  • 肝硬変患者における血中亜鉛の検討
    小川 浩司, 鈴木 和治, 中村 晃久, 大原 正嗣, 川岸 直樹, 出水 孝章, 梅村 真知子, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉 肝臓 58 (Suppl.3) A779 -A779 2017年11月 [査読無し][通常論文]
  • 慢性肝疾患患者のそう痒症状に対するナルフラフィンの治療効果の検討
    鈴木 和治, 中井 正人, 中村 晃久, 大原 正嗣, 川岸 直樹, 出水 孝章, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉 肝臓 58 (Suppl.3) A788 -A788 2017年11月 [査読無し][通常論文]
  • C型肝炎のDAAs治療における脂質、糖代謝の変化の検討
    川岸 直樹, 鈴木 和治, 中村 晃久, 大原 正嗣, 出水 孝章, 梅村 真知子, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉 肝臓 58 (Suppl.3) A813 -A813 2017年11月 [査読無し][通常論文]
  • DAA治療非著効により獲得される耐性変異の検討
    伊藤 淳, 大原 正嗣, 川岸 直樹, 出水 孝章, 梅村 真知子, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉 肝臓 58 (Suppl.2) A589 -A589 2017年09月 [査読無し][通常論文]
  • NBNC肝癌の臨床的特徴
    小川 浩司, 中村 晃久, 鈴木 和治, 大原 正嗣, 川岸 直樹, 出水 孝章, 梅村 真知子, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉 肝臓 58 (Suppl.2) A604 -A604 2017年09月 [査読無し][通常論文]
  • 核酸アナログ製剤によるHBs抗原の低下作用
    小川 浩司, 中村 晃久, 鈴木 和治, 大原 正嗣, 川岸 直樹, 出水 孝章, 梅村 真知子, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉 肝臓 58 (Suppl.2) A616 -A616 2017年09月 [査読無し][通常論文]
  • 肝硬変患者における筋肉量測定方法の検討
    大原 正嗣, 鈴木 和治, 中村 晃久, 川岸 直樹, 出水 孝章, 梅村 真知子, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉 肝臓 58 (Suppl.2) A633 -A633 2017年09月 [査読無し][通常論文]
  • 岩井 孝仁, 西田 睦, 表原 里実, 薮崎 哲史, 小川 浩司, 岡村 圭祐, 平野 聡, 三橋 智子, 加畑 馨, 清水 力 超音波医学 44 (5) 447 -455 2017年09月 [査読有り][通常論文]
     
    症例は40歳代女性.主訴なし.前医にて肝S6の孤立性壊死性結節を経過観察中であった.造影CTにて,肝S6結節は経時的にほぼ消失したが,新たに肝S5に早期濃染を伴う10mmの腫瘤性病変を指摘された.超音波検査(US)とGd-EOB-DTPA造影MRIを施行し,悪性病変を否定できず,切除希望のため当院紹介となった.当院での初回USにて,肝S5に境界不明瞭な低エコー腫瘤を認め,Sonazoid造影超音波検査(CEUS)では,動脈相で微細点状の豊富な造影効果を認め,その後,結節状に強く造影された.門脈相で造影効果は遷延し,後血管相で造影効果は認めなかった.半年後のUSにて,肝S5腫瘤に増大はみられず,CEUS動脈相,後血管相に著変はなかったが,門脈相で早期の造影効果減弱を認めた.造影CTでも門脈相,平衡相の洗い出しが明瞭化した.これらの変化は肝細胞癌の脱分化など悪性病変を否定できず,腹腔鏡下肝部分切除術が施行された.病理組織学的所見では,被膜を有さない境界明瞭な腫瘤で,炎症細胞浸潤を背景に小血管の増生を伴っていた.免疫染色でαSMA陽性,ALK陰性,EBER陰性,IgG4陽性細胞をほとんど認めず,炎症性偽腫瘍(IPT)と診断された.IPTは特徴的な画像所見に乏しく,CEUSでIPTを経過観察し得た報告は少ない.今回,経時的にCEUS所見が変化したIPTの1症例を経験したので,若干の文献的考察を含めて報告する.(著者抄録)
  • NASH診療の現状と問題点 非アルコール性脂肪性肝疾患診断における問題点
    小川 浩司, 荘 拓也, 坂本 直哉 肝臓 58 (Suppl.1) A106 -A106 2017年04月 [査読無し][通常論文]
  • C型肝炎の治療到達点と新たな課題 HIV/HCV重複感染の現状とIFN-based therapyおよびDAA therapyの治療効果
    荘 拓也, 小川 浩司, 坂本 直哉 日本消化器病学会雑誌 114 (臨増総会) A59 -A59 2017年03月 [査読無し][通常論文]
  • C型肝炎撲滅に向けた地域の取り組み 肝炎ウイルス陽性者アラートシステムによるC型肝炎受診率向上効果
    小川 浩司, 荘 拓也, 坂本 直哉 肝臓 57 (Suppl.3) A693 -A693 2016年10月 [査読無し][通常論文]
  • 肝不全治療の新たな展開 肝硬変患者に対するカルニチン製剤の有用性および初回投与量の検討
    小川 浩司, 須田 剛生, 坂本 直哉 肝臓 57 (Suppl.3) A674 -A674 2016年10月 [査読無し][通常論文]
  • 森川賢一, 小川浩司, 坂本直哉 日本消化器がん検診学会雑誌 54 (Supplement) 910 -A454 2016年09月15日 [査読無し][通常論文]
  • 核酸アナログ製剤によるHBs抗原の低下作用
    小川 浩司, 大原 正嗣, 川岸 直樹, 梅村 真知子, 出水 孝章, 伊藤 淳, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉 肝臓 57 (Suppl.2) A530 -A530 2016年09月 [査読無し][通常論文]
  • 進行肝細胞癌におけるSorafenib+5-FU併用療法の検討
    荘 拓也, 小川 浩司, 出水 孝章, 梅村 真知子, 伊藤 淳, 常松 聖司, 佐藤 史幸, 中井 正人, 須田 剛生, 森川 賢一, 坂本 直哉 The Liver Cancer Journal 8 (1) 58 -59 2016年06月 [査読無し][通常論文]
  • 肝臓における超音波組織弾性測定の機種間差の検討 Shear wave with Smart mapsとFibroScanとの比較
    若林 倭, 工藤 悠輔, 西田 睦, 堀江 達則, 岩井 孝仁, 表原 里実, 佐藤 恵美, 高杉 莉佳, 小川 浩司, 坂本 直哉 超音波医学 43 (1) 131 -132 2016年01月 [査読無し][通常論文]
  • 肝移植後C型肝炎患者に対するダクラタスビル・アスナプレビル併用療法の検討
    小川 浩司, 梅村 真知子, 出水 孝章, 伊藤 淳, 佐藤 史幸, 常松 聖司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉, 嶋村 剛 肝臓 56 (Suppl.3) A981 -A981 2015年11月 [査読無し][通常論文]
  • 小児の肝疾患 臨床・研究のup to date 当院におけるFontan術後の肝合併症の現状
    荘 拓也, 小川 浩司, 坂本 直哉 日本消化器病学会雑誌 112 (臨増大会) A637 -A637 2015年09月 [査読無し][通常論文]
  • 単純性脂肪肝と非アルコール性脂肪性肝炎の臨床的検討
    寺下 勝巳, 小川 浩司, 伊藤 淳, 佐藤 史幸, 常松 聖司, 佃 曜子, 中井 正人, 荘 拓也, 須田 剛気, 森川 健一, 坂本 直哉 肝臓 56 (Suppl.2) A756 -A756 2015年09月 [査読無し][通常論文]
  • 肝動注化学療法における早期治療効果予測因子に関する検討
    常松 聖司, 須田 剛生, 伊藤 淳, 佐藤 史幸, 寺下 勝巳, 佃 曜子, 中井 正人, 荘 拓也, 夏井坂 光輝, 小川 浩司, 坂本 直哉 肝臓 56 (Suppl.1) A285 -A285 2015年04月 [査読無し][通常論文]
  • ヒト初代B細胞におけるHCVcc感染
    中井 正人, 伊藤 淳, 常松 聖司, 佐藤 史幸, 佃 曜子, 寺下 勝巳, 荘 拓也, 須田 剛生, 夏井坂 光輝, 小川 浩司, フセイン・ハッサン・アリ, 松本 美佐子, 瀬谷 司, 坂本 直哉 日本消化器病学会雑誌 112 (臨増総会) A354 -A354 2015年03月 [査読無し][通常論文]
  • 当院におけるフォンタン術後患者の肝合併症の現状
    荘 拓也, 小川 浩司, 伊藤 淳, 佐藤 史幸, 常松 聖司, 佃 曜子, 寺下 勝巳, 中井 正人, 須田 剛生, 夏井坂 光輝, 坂本 直哉, 泉 岳, 武田 充人, 有賀 正 肝臓 55 (Suppl.3) A855 -A855 2014年10月 [査読無し][通常論文]
  • L-カルニチンのC型肝炎ウイルス増殖抑制効果に関する研究
    佃 曜子, 伊藤 淳, 常松 聖司, 佐藤 史幸, 寺下 勝巳, 中井 正人, 堀本 啓大, 荘 拓也, 須田 剛生, 夏井坂 光輝, 小川 浩司, 中馬 誠, 坂本 直哉 日本消化器病学会雑誌 111 (臨増大会) A916 -A916 2014年09月 [査読無し][通常論文]
  • 非代償性肝硬変に伴う胸腹水および肝腎症候群に対するトルバプタン使用例の検討
    中井 正人, 伊藤 淳, 佃 曜子, 寺下 勝巳, 荘 拓也, 須田 剛生, 夏井坂 光輝, 小川 浩司, 坂本 直哉 肝臓 55 (Suppl.2) A670 -A670 2014年09月 [査読無し][通常論文]
  • 肝がん治療戦略のUp to Date 進行肝細胞癌に対する分子標的治療、肝動注療法の位置づけと今後の展開
    中馬 誠, 山本 義也, 小川 浩司, 荘 拓也, 佃 曜子, 目黒 高志, 永坂 敦, 中村 路夫, 工藤 峰生, 武藤 修一, 上林 実, 曽我部 進, 宮城島 拓人, 中西 満, 坂本 直哉 日本癌治療学会誌 49 (3) 790 -790 2014年06月 [査読無し][通常論文]
  • 肝内胆管癌におけるZEB1、EMT関連分子の臨床病理学的検討
    寺下 勝巳, 畑中 佳奈子, 畑中 豊, 三橋 智子, 横尾 英樹, 大村 卓味, 石津 寛之, 永坂 敦, 山本 義也, 小川 浩司, 倉内 宣明, 豊田 秀徳, 熊田 卓, 金岡 祐次, 堀本 啓大, 荘 拓也, 夏井坂 光輝, 神山 俊哉, 武冨 紹信, 坂本 直哉 肝臓 55 (Suppl.1) A335 -A335 2014年04月 [査読無し][通常論文]
  • 梅村 真知子, 渡邉 豊, 小川 浩司, 山本 義也, 矢和田 敦, 榮浪 克也, 長佐古 友和, 川村 直之, 工藤 峰生, 松林 桂二, 狩野 吉康, 姜 貞憲, 水尾 仁志, 岡本 宏明, 高橋 和明, 安倍 夏生, 新井 雅裕, 三代 俊治 肝臓 55 (6) 349 -359 2014年 [査読有り][通常論文]
     
    2007〜10年の4年間に、函館市内4病院で診療した13例、函館市内で感染し札幌で発症した1例の計14例のE型肝炎ウイルス(HEV)感染者を対象とし、E型肝炎の臨床像、感染経路の解析およびウイルス遺伝子の系統解析を行った。道南地区における有症状の非A非B非C型急性肝炎のうちE型の頻度は24.2%であった。E型肝炎14(男8:女6)例中、4(男1:女3)例が重症化しそのうち3例は劇症肝炎を呈し2例は死亡した。13例から分離されたHEV RNAゲノムのORF1 326塩基に対し遺伝子系統解析を行ったところ、3株はgenotype 3、10株はgenotype 4に属した。genotype 4の7株は既報のKitami/Abashiri strainに、2株は札幌圏小流行を起こしたNew Sapporo strainに属した。患者の職業、食肉嗜好、居住地等は共通点に乏しかった。感染源として、従来から指摘されている動物の内臓肉に加え、生の貝類が疑われた。(著者抄録)
  • 分子標的薬と殺細胞性薬剤併用による治療効果増強の検証 高度進行肝癌に対する5-FU+ソラフェニブ併用療法の臨床第I相試験
    荘 拓也, 中西 満, 中馬 誠, 中村 路夫, 永坂 敦, 小川 浩司, 山本 義也, 目黒 高志, 常松 聖司, 佐藤 史幸, 佃 曜子, 寺下 勝巳, 中井 正人, 小林 智絵, 夏井坂 光輝, 髭 修平, 坂本 直哉 The Liver Cancer Journal 5 (2) 142 -143 2013年06月 [査読無し][通常論文]
  • 高度進行肝癌に対する5-FU+ソラフェニブ併用療法の臨床第I相試験 分子標的薬と殺細胞性薬剤併用による治療効果増強の検証
    中西 満, 中馬 誠, 髭 修平, 中村 路夫, 小川 浩司, 常松 聖司, 佃 曜子, 寺下 勝巳, 中井 正人, 小林 智絵, 荘 拓也, 山本 義也, 永坂 敦, 目黒 高志, 坂本 直哉 肝臓 53 (Suppl.1) A406 -A406 2012年04月 [査読無し][通常論文]
  • 小川 浩司, 山本 義也, 梅村 真知子, 姜 貞憲, 坂田 秀勝, 松林 圭二, 高橋 和明, 新井 雅裕, 三代 俊治 肝臓 53 (4) 206 -215 2012年04月 [査読無し][通常論文]
     
    2010年春函館地区ではE型劇症肝炎2例が同時期に発生したが、分離同定されたE型肝炎ウイルス(HEV)株(JFI-Hak10、JFS-Hak10)は何れもGenotype 4に属し、遺伝子系統解析により2009年秋に発生したE型急性肝炎札幌圏小流行で分離された"new Sapporo strain"と近縁な同一系統株であることが判明した。症例は63歳と73歳のいずれも女性で2010年3月下旬に発症し4月上旬に函館市内の2病院に入院となった。症例1は劇症肝炎急性型を呈するも速やかに改善し第22病日退院となった。しかし症例2は肝炎が遷延し劇症肝炎亜急性型を呈し第50病日死亡した。血中HEV RNAをretrospectiveに定量したところ生存例ではウイルス量が順調に減衰したが、死亡例では血中HEV RNA量の減衰を認めず、肝炎の遷延化に関連し不幸な転帰につながった可能性が考えられた。(著者抄録)
  • C型肝炎患者に対するリバビリン単独投与における貧血と血小板増加効果
    小林 智絵, 髭 修平, 寺下 勝巳, 中井 正人, 堀本 啓大, 荘 拓也, 中西 満, 小川 浩司, 中馬 誠 日本消化器病学会雑誌 109 (臨増総会) A313 -A313 2012年03月 [査読無し][通常論文]
  • HCVコアアミノ酸置換とPEG-IFN/リバビリン併用療法施行C型慢性肝炎症例の検討
    小林 智絵, 髭 修平, 荘 拓也, 中西 満, 中馬 誠, 浅香 正博, 永坂 敦, 小川 浩司, 山本 義也 肝臓 51 (Suppl.1) A226 -A226 2010年04月 [査読無し][通常論文]
  • 1型高ウイルス量C型肝炎に対するPEG-IFN/RBV併用療法の有効性の検討
    小林 智絵, 髭 修平, 荘 拓也, 中西 満, 中馬 誠, 浅香 正博, 小川 浩司, 山本 義也, 永坂 敦 日本消化器病学会雑誌 107 (臨増総会) A223 -A223 2010年03月 [査読無し][通常論文]
  • 畑中一映, 林秀幸, 中井正人, 井上弘行, 小川浩司, 山本文泰, 山本義也, 片桐雅樹, 成瀬宏仁, 工藤和洋, 坂田幸雄, 辻龍一, 小松嘉人 日本癌治療学会誌 43 (2) 935 -935 2008年10月01日 [査読無し][通常論文]
  • 中積 宏之, 川本 泰之, 江藤 和範, 小川 浩司, 山本 文泰, 畑中 一映, 山本 義也, 片桐 雅樹, 成瀬 宏仁 函館医学誌 31 (1) 8 -11 2007年10月 [査読無し][通常論文]
     
    肝肉芽腫は肝生検施行例の２～15％に認められるといわれている。その原因疾患は原発性胆汁性肝硬変（PBC），サルコイドーシス，結核，薬剤などさまざまであり，特定できないこともある。Hodgkin Lymphoma（HL）も肝肉芽腫をきたしうる疾患であるが比較的稀である。今回，肝サルコイドーシスとの鑑別を要し診断に苦慮したHL の１例を経験したので，若干の文献的考察を加え報告する。
  • 川本 泰之, 江藤 和範, 中積 宏之, 小川 浩司, 山本 文泰, 畑中 一映, 山本 義也, 片桐 雅樹, 成瀬 宏仁 函館医学誌 31 (1) 12 -15 2007年10月 [査読無し][通常論文]
     
    Churg-Strauss 症候群は，気管支喘息，好酸球増多，血管炎症候群を３主徴とする症候群で比較的まれな疾患である。病理組織学的には壊死性血管炎のほかに，肉芽腫性血管炎および血管外肉芽腫が認められることが特徴で，1951年にChurg とStrauss が結節性多発動脈炎から本症を独立させた１）～４）。肉芽腫性病変は全身に出現し，皮膚症状として紫斑，皮下出血など，循環器症状として心不全，心筋梗塞など，呼吸器症状として間質性肺炎，胸膜炎など，その他，筋炎，関節炎など症状は多彩である。消化器症状としては穿孔，出血，腹膜炎があり，これらを合併したときは予後不良と報告されている５）６）。今回我々は，腹腔内出血をきたしたChurg-Strauss 症候群の１例を経験したので報告する。
  • 悪性腹膜中皮腫の3例
    畑中 一映, 中井 正人, 小松 康之, 江藤 和範, 小川 浩司, 山本 文泰, 山本 義也, 片桐 雅樹, 成瀬 宏仁, 下山 則彦, 小松 嘉人 日本癌治療学会誌 42 (2) 827 -827 2007年09月 [査読無し][通常論文]
  • 当科における胃瘻症例の検討
    片桐 雅樹, 江藤 和範, 川本 泰之, 中積 宏之, 小川 浩司, 山本 文泰, 畑中 一映, 山本 義也, 成瀬 宏仁 道南医学会大会並びに総会プログラム・抄録集 59回 27 -27 2006年11月 [査読無し][通常論文]
  • 進行・再発大腸癌に対するFOLFOX治療例の検討
    畑中 一映, 江藤 和範, 川本 泰之, 中積 宏之, 小川 浩司, 山本 文泰, 山本 義也, 片桐 雅樹, 成瀬 宏仁, 遠山 茂, 木村 純 道南医学会大会並びに総会プログラム・抄録集 59回 30 -30 2006年11月 [査読無し][通常論文]
  • 胆嚢癌肝門部浸潤に伴う胆管炎の制御にENBD side by side留置が有効であった1例
    成瀬 宏仁, 江藤 和範, 川本 泰之, 中積 宏之, 小川 浩司, 山本 文泰, 畑中 一映, 山本 義也, 片桐 雅樹 道南医学会大会並びに総会プログラム・抄録集 59回 31 -31 2006年11月 [査読無し][通常論文]
  • 当院におけるB型慢性肝疾患に対する抗ウイルス治療の現状
    山本 義也, 江藤 和範, 川本 泰之, 中積 宏之, 小川 浩司, 山本 文泰, 畑中 一映, 片桐 雅樹, 成瀬 宏仁 道南医学会大会並びに総会プログラム・抄録集 59回 32 -32 2006年11月 [査読無し][通常論文]
  • 当科における切除不能膵癌に対する塩酸ゲムシタビンによる化学療法の成績
    成瀬 宏仁, 中積 宏之, 川本 泰之, 江藤 和範, 小川 浩司, 山本 文康, 畑中 一映, 山本 義也, 片桐 雅樹 日本消化器病学会雑誌 103 (臨増大会) A990 -A990 2006年09月 [査読無し][通常論文]
  • MGBプローブ法によるHBV変異株の定量
    山本 洋一, 髭 修平, 荘 拓也, 夏井坂 光輝, 小川 浩司, 中西 満, 中馬 誠, 吉田 繁, 浅香 正博 肝臓 47 (Suppl.2) A389 -A389 2006年09月 [査読無し][通常論文]

教育活動情報

主要な担当授業

  • 基本医学研究
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 肝炎ウイルス、癌ゲノミクス、H.pylori、食道癌 Hepatitis viruses、Cancer genomics、H.pylori、Esophageal cancer
  • 基本医学総論
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 肝炎ウイルス、癌ゲノミクス、H.pylori、分子標的療法 Hepatitis viruses、Cancer genomics、H.pylori、Molecular targeting therapies
  • 医学総論
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 肝炎ウイルス、癌ゲノミクス、H.pylori、食道癌、膵癌、炎症性腸疾患
  • 基盤医学研究
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 肝炎ウイルス、癌ゲノミクス、H.pylori、分子標的療法、がんプロフェッショナル
  • 臨床医学研究
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 肝炎ウイルス、癌ゲノミクス、H.pylori、食道癌、膵癌、炎症性腸疾患

Copyright © MEDIA FUSION Co.,Ltd. All rights reserved.