C型肝炎に対する肝移植後長期経過症例に対する経口抗ウイルス薬療法の経験
「I. 緒言」C型肝炎ウイルス(hepatitis C virus : HCV)による肝硬変, 肝細胞がんに対する肝移植後には, 肝炎の再発がほぼ全例に認められ, グラフト喪失の主な原因である. 肝移植後再発C型肝炎に対してインターフェロン(interferon : IFN)を含んだ治療が行われてきたが奏効率は30-40%程度と報告され, 拒絶反応発症のリスクもあり, 再発肝炎治療は困難であった. 近年, simeprevir(SMV), daclatasvir(DCV), asunaprevir(ASV)などの直接作用型抗ウイルス薬(direct acting antiviral agent...
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| Published in | Japanese Journal of Transplantation Vol. 52; no. 1; pp. 081 - 086 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本移植学会
2017
日本移植学会 The Japan Society for Transplantation |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0578-7947 2188-0034 |
| DOI | 10.11386/jst.52.1_081 |
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| Abstract | 「I. 緒言」C型肝炎ウイルス(hepatitis C virus : HCV)による肝硬変, 肝細胞がんに対する肝移植後には, 肝炎の再発がほぼ全例に認められ, グラフト喪失の主な原因である. 肝移植後再発C型肝炎に対してインターフェロン(interferon : IFN)を含んだ治療が行われてきたが奏効率は30-40%程度と報告され, 拒絶反応発症のリスクもあり, 再発肝炎治療は困難であった. 近年, simeprevir(SMV), daclatasvir(DCV), asunaprevir(ASV)などの直接作用型抗ウイルス薬(direct acting antiviral agents : DAAs)を用いた抗HCV療法が本邦でも認可された. 肝移植が施行されていない患者に対するSMV, peg-IFN, ribavirin(RBV)の3剤併用療法(SMV+peg-IFN+RBV療法)や, DCV, ASVの2剤併用療法(DCV+ASV療法)の良好な治療効果が報告されている. |
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| AbstractList | 「I. 緒言」C型肝炎ウイルス(hepatitis C virus : HCV)による肝硬変, 肝細胞がんに対する肝移植後には, 肝炎の再発がほぼ全例に認められ, グラフト喪失の主な原因である. 肝移植後再発C型肝炎に対してインターフェロン(interferon : IFN)を含んだ治療が行われてきたが奏効率は30-40%程度と報告され, 拒絶反応発症のリスクもあり, 再発肝炎治療は困難であった. 近年, simeprevir(SMV), daclatasvir(DCV), asunaprevir(ASV)などの直接作用型抗ウイルス薬(direct acting antiviral agents : DAAs)を用いた抗HCV療法が本邦でも認可された. 肝移植が施行されていない患者に対するSMV, peg-IFN, ribavirin(RBV)の3剤併用療法(SMV+peg-IFN+RBV療法)や, DCV, ASVの2剤併用療法(DCV+ASV療法)の良好な治療効果が報告されている. Liver cirrhosis resulting from the recurrence of hepatitis in patients with hepatitis C virus (HCV) is the major cause of graft loss after liver transplantation (LT). The effectiveness of treatment by direct-acting antiviral agents (DAAs) against HCV has been reported in LT patients. We report our experiences of anti-HCV therapy using DAAs in long-term HCV recipients. Five patients treated with DAAs were included in this study. Two patients were treated with pegylated-interferon (peg-IFN), ribavirin (RBV), and simeprevir (SMV), and three were with daclatasvir (DCV) and asunaprevir (ASV). All five had been previously treated with interferon (IFN) or peg-IFN with RBV after LT. Four of them discontinued antiviral therapy because of heart failure, retinal detachment, cellulitis, or diabetes mellitus. HCV reappearance was experienced after in the remaining patient who continued the therapy. In all patients, the levels of serum HCV-ribo nucleic acid were decreased to the under-detection level within 15 weeks; sustained virological response 24 weeks after treatment (SVR24) was then achieved. HCV could be eradicated with DAAs therapy even in long-term LT patients with failed IFN. |
| Author | 増田, 雄一 三田, 篤義 池上, 俊彦 中澤, 勇一 小山, 誠 宮川, 眞一 大野, 康成 小林, 聡 浦田, 浩一 細田, 清孝 |
| Author_FL | NAKAZAWA Yuichi KOYAMA Makoto MITA Atsuyoshi KOBAYASHI Akira OHNO Yasunari IKEGAMI Toshihiko MIYAGAWA Shin-ichi MASUDA Yuichi HOSODA Kiyotaka URATA Koichi |
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| References | 17) Burton JR Jr, O'Leary JG, Verna EC, et al. A US multicenter study of hepatitis C treatment of liver transplant recipients with protease-inhibitor triple therapy. J Hepatol 2014; 61: 508-514. 18) Fridell RA, Qiu D, Wang C, et al. Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system. Antimicrob Agents Chemother 2010; 54: 3641-3650. 21) Kawaoka T, Imamura M, Morio K, et al. Three patients treated with daclatasvir and asunaprevir for recurrent hepatitis C after liver transplantation: case report. Hepatol Res 2016; 46: 707-712. 1) Ahmad J, Dodson SF, Demetris AJ, et al. Recurrent hepatitis C after liver transplantation: a nonrandomized trial of interferon alfa alone versus interferon alfa and ribavirin. Liver Transpl 2001; 7: 863-869. 4) Herzer K, Gerken G. Hepatitis C virus reinfection after liver transplant: new chances and new challenges in the era of direct-acting antiviral agents. World J Hepatol 2015; 7: 532-538. 8) Ueda Y, Kaido T, Hatano E, et al. Safe and effective treatment with daclatasvir and asunaprevir in a liver transplant recipient with severe cholestatic hepatitis C. Hepatol Res 2015; 45: 1360-1362. 12) Crespo G, Mariño Z, Navasa M, et al. Viral hepatitis in liver transplantation. Gastroenterology 2012; 142: 1373-1383. 14) Féray C, Samuel D, Gigou M, et al. An open trial of interferon alfa recombinant for hepatitis C after liver transplantation: antiviral effects and risk of rejection. Hepatology 1995; 22: 1084-1089. 11) 上田佳秀， 丸澤宏之. 肝移植後の抗ウイルス療法の新展開. 肝胆膵 2014; 69: 889-894. 20) LaMattina JC, Mezrich JD, Fernandez LA, et al. Native kidney function following liver transplantation using calcineurin inhibitors: single-center analysis with 20 years of follow-up. Clinical Transplant 2013; 27: 193-202. 7) Kawaoka T, Imamura M, Kan H, et al. Two patients treated with simeprevir plus pegylated-interferon and ribavirin triple therapy for recurrent hepatitis C after living donor liver transplantation: case report. Transplant Proc 2015; 47: 809-814. 19) Mcphee F, Friborg j, Levine S, et al. Resistance analysis of the hepatitis C virus NS3 protease inhibitor asunaprevir. Antimicrob Agents Chemother 2012; 56: 3670-3681. 6) Manns M, Pol S, Jacobson IM, et al. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet 2014; 384: 1597-1605. 10) 日本肝移植研究会. 肝移植症例登録報告. 移植 2015; 50: 156-169. 9) Zoulim F, Liang TJ, Gerbes AL, et al. Hepatitis C virus treatment in the real world: optimising treatment and access to therapies. Gut 2015; 64: 1824-1833. 13) Berenguer M, Ferrell L, Watson J, et al. HCV-related fibrosis progression following liver transplantation: increase in recent years. J Hepatol 2000; 32: 673-684. 3) Berenguer M, Schuppan D. Progression of liver fibrosis in post-transplant hepatitis C: mechanisms, assessment and treatment. J Hepatol 2013; 58: 1028-1041. 2) Wang CS, Ko HH, Yoshida EM, et al. Interferon-based combination anti-viral therapy for hepatitis C virus after liver transplantation: a review and quantitative analysis. Am J Transplant 2006; 6: 1586-1599. 15) Stravitz RT, Shiffman ML, Sanyal AJ, et al. Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation. Liver Transpl 2004; 10: 850-858. 5) Jacobson IM, Dore GJ, Foster GR, et al. Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1) : a phase 3, randomised, double-blind, placebo-controlled trial. Lancet 2014; 384: 403-413. 16) Pungpapong S, Aqel BA, Koning L, et al. Multicenter experience using telaprevir or boceprevir with peginterferon and ribavirin to treat hepatitis C genotype 1 after liver transplantation. Liver Transpl 2013; 19: 690-700. |
| References_xml | – reference: 15) Stravitz RT, Shiffman ML, Sanyal AJ, et al. Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation. Liver Transpl 2004; 10: 850-858. – reference: 16) Pungpapong S, Aqel BA, Koning L, et al. Multicenter experience using telaprevir or boceprevir with peginterferon and ribavirin to treat hepatitis C genotype 1 after liver transplantation. Liver Transpl 2013; 19: 690-700. – reference: 18) Fridell RA, Qiu D, Wang C, et al. Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system. Antimicrob Agents Chemother 2010; 54: 3641-3650. – reference: 2) Wang CS, Ko HH, Yoshida EM, et al. Interferon-based combination anti-viral therapy for hepatitis C virus after liver transplantation: a review and quantitative analysis. Am J Transplant 2006; 6: 1586-1599. – reference: 11) 上田佳秀， 丸澤宏之. 肝移植後の抗ウイルス療法の新展開. 肝胆膵 2014; 69: 889-894. – reference: 20) LaMattina JC, Mezrich JD, Fernandez LA, et al. Native kidney function following liver transplantation using calcineurin inhibitors: single-center analysis with 20 years of follow-up. Clinical Transplant 2013; 27: 193-202. – reference: 8) Ueda Y, Kaido T, Hatano E, et al. Safe and effective treatment with daclatasvir and asunaprevir in a liver transplant recipient with severe cholestatic hepatitis C. Hepatol Res 2015; 45: 1360-1362. – reference: 5) Jacobson IM, Dore GJ, Foster GR, et al. Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1) : a phase 3, randomised, double-blind, placebo-controlled trial. Lancet 2014; 384: 403-413. – reference: 1) Ahmad J, Dodson SF, Demetris AJ, et al. Recurrent hepatitis C after liver transplantation: a nonrandomized trial of interferon alfa alone versus interferon alfa and ribavirin. Liver Transpl 2001; 7: 863-869. – reference: 21) Kawaoka T, Imamura M, Morio K, et al. Three patients treated with daclatasvir and asunaprevir for recurrent hepatitis C after liver transplantation: case report. Hepatol Res 2016; 46: 707-712. – reference: 17) Burton JR Jr, O'Leary JG, Verna EC, et al. A US multicenter study of hepatitis C treatment of liver transplant recipients with protease-inhibitor triple therapy. J Hepatol 2014; 61: 508-514. – reference: 7) Kawaoka T, Imamura M, Kan H, et al. Two patients treated with simeprevir plus pegylated-interferon and ribavirin triple therapy for recurrent hepatitis C after living donor liver transplantation: case report. Transplant Proc 2015; 47: 809-814. – reference: 13) Berenguer M, Ferrell L, Watson J, et al. HCV-related fibrosis progression following liver transplantation: increase in recent years. J Hepatol 2000; 32: 673-684. – reference: 14) Féray C, Samuel D, Gigou M, et al. An open trial of interferon alfa recombinant for hepatitis C after liver transplantation: antiviral effects and risk of rejection. Hepatology 1995; 22: 1084-1089. – reference: 10) 日本肝移植研究会. 肝移植症例登録報告. 移植 2015; 50: 156-169. – reference: 6) Manns M, Pol S, Jacobson IM, et al. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet 2014; 384: 1597-1605. – reference: 9) Zoulim F, Liang TJ, Gerbes AL, et al. Hepatitis C virus treatment in the real world: optimising treatment and access to therapies. Gut 2015; 64: 1824-1833. – reference: 3) Berenguer M, Schuppan D. Progression of liver fibrosis in post-transplant hepatitis C: mechanisms, assessment and treatment. J Hepatol 2013; 58: 1028-1041. – reference: 4) Herzer K, Gerken G. Hepatitis C virus reinfection after liver transplant: new chances and new challenges in the era of direct-acting antiviral agents. World J Hepatol 2015; 7: 532-538. – reference: 19) Mcphee F, Friborg j, Levine S, et al. Resistance analysis of the hepatitis C virus NS3 protease inhibitor asunaprevir. Antimicrob Agents Chemother 2012; 56: 3670-3681. – reference: 12) Crespo G, Mariño Z, Navasa M, et al. Viral hepatitis in liver transplantation. Gastroenterology 2012; 142: 1373-1383. |
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| Snippet | 「I. 緒言」C型肝炎ウイルス(hepatitis C virus : HCV)による肝硬変, 肝細胞がんに対する肝移植後には, 肝炎の再発がほぼ全例に認められ, グラフト喪失の主な原因である. 肝... Liver cirrhosis resulting from the recurrence of hepatitis in patients with hepatitis C virus (HCV) is the major cause of graft loss after liver... |
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| SubjectTerms | direct-acting antiviral agents liver transplantation recurrent hepatitis C |
| Title | C型肝炎に対する肝移植後長期経過症例に対する経口抗ウイルス薬療法の経験 |
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