サブジェノタイプ1bのC型慢性肝炎及びC型代償性肝硬変患者に対するオムビタスビル/パリタプレビル/リトナビル配合錠の特定使用成績調査：国内臨床試験長期追跡調査

オムビタスビル/パリタプレビル/リトナビル配合剤（以下；本剤）の特定使用成績調査を実施し，インターフェロンフリー直接作用型抗ウイルス薬治療後の持続性ウイルス学的著効（SVR）維持と肝発癌状況を調査した．本剤第II相又は第III相臨床試験の後観察期間（48週）を完了したサブジェノタイプ1bのC型慢性肝炎およびC型代償性肝硬変患者を対象に，4年間追跡調査した．330例の有効性解析対象症例のうち，後観察期間を合わせた5年間のSVR維持率は100%であった．5年間に10例で肝発癌が報告され，累積発癌割合（95%CI）は3.2%（1.73-5.87）で，SVR12達成例で未達成例に比べ有意に低かった．安...

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Published in肝臓 Vol. 63; no. 7; pp. 319 - 334
Main Authors 川名, 克芳, 島上, 哲朗, 佐久間, 龍太, 黄地, 薫, 熊田, 博光, 持田, 智
Format Journal Article
LanguageJapanese
Published 一般社団法人　日本肝臓学会 01.07.2022
Subjects
C型慢性肝炎
オムビタスビル/パリタプレビル/リトナビル配合錠
サブジェノタイプ1b
肝癌
長期追跡調査
Online AccessGet full text
ISSN0451-4203
1881-3593
DOI10.2957/kanzo.63.319

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Abstract オムビタスビル/パリタプレビル/リトナビル配合剤（以下；本剤）の特定使用成績調査を実施し，インターフェロンフリー直接作用型抗ウイルス薬治療後の持続性ウイルス学的著効（SVR）維持と肝発癌状況を調査した．本剤第II相又は第III相臨床試験の後観察期間（48週）を完了したサブジェノタイプ1bのC型慢性肝炎およびC型代償性肝硬変患者を対象に，4年間追跡調査した．330例の有効性解析対象症例のうち，後観察期間を合わせた5年間のSVR維持率は100%であった．5年間に10例で肝発癌が報告され，累積発癌割合（95%CI）は3.2%（1.73-5.87）で，SVR12達成例で未達成例に比べ有意に低かった．安全性解析対象症例334例中，25例（7.5%）に重篤な有害事象が認められた．本研究により，本剤治療後5年間にわたりSVRが維持され，SVR12達成により肝発癌が低下することが示唆された．
AbstractList オムビタスビル/パリタプレビル/リトナビル配合剤（以下；本剤）の特定使用成績調査を実施し，インターフェロンフリー直接作用型抗ウイルス薬治療後の持続性ウイルス学的著効（SVR）維持と肝発癌状況を調査した．本剤第II相又は第III相臨床試験の後観察期間（48週）を完了したサブジェノタイプ1bのC型慢性肝炎およびC型代償性肝硬変患者を対象に，4年間追跡調査した．330例の有効性解析対象症例のうち，後観察期間を合わせた5年間のSVR維持率は100%であった．5年間に10例で肝発癌が報告され，累積発癌割合（95%CI）は3.2%（1.73-5.87）で，SVR12達成例で未達成例に比べ有意に低かった．安全性解析対象症例334例中，25例（7.5%）に重篤な有害事象が認められた．本研究により，本剤治療後5年間にわたりSVRが維持され，SVR12達成により肝発癌が低下することが示唆された．
Author 川名, 克芳
島上, 哲朗
持田, 智
黄地, 薫
熊田, 博光
佐久間, 龍太
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  fullname: 佐久間, 龍太
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  fullname: 黄地, 薫
  organization: アッヴィ合同会社医学統括本部
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  organization: 虎の門病院
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  fullname: 持田, 智
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References 11) Ioannou GN, Green PK, Berry K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol 2018; 68: 25-32
31) Simili A, Mazzella G, Ravaioli F, et al. Interleukin 28 Polymorphisms and Hepatocellular Carcinoma Development after Direct Acting Antiviral Therapy for Chronic Hepatitis C. J Gastrointestin Liver Dis 2019; 28: 449-456
5) 国立がん研究センター. がん情報サービス. https://ganjoho.jp/reg_stat/statistics/stat/summary.html (2021年11月22日参照
6) 工藤正俊, 泉 並木, 久保正二, 他. 第22回全国原発性肝癌追跡調査報告 (2012～2013) 日本肝癌研究会追跡調査委員会. 肝臓 2021; 62: 251-299
12) Morgan RL, Baack B, Smith BD, et al. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med 2013; 158: 329-337
15) Tanaka H, Tsukuma H, Kasahara A, et al. Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C: a retrospective cohort study of 738 patients. Int J Cancer 2000; 87: 741-749
29) Watanabe T, Tokumoto Y, Joko K, et al. Predictors of hepatocellular carcinoma occurrence after direct-acting antiviral therapy in patients with hepatitis C virus infection. Hepatol Res 2019; 49: 136-146
30) De Re V, Tornesello ML, De Zorzi M, et al. Clinical Significance of Polymorphisms in Immune Response Genes in Hepatitis C-Related Hepatocellular Carcinoma. Front Microbiol 2019; 10: 475
23) Simmons B, Saleem J, Hill A, et al. Risk of Late Relapse or Reinfection With Hepatitis C Virus After Achieving a Sustained Virological Response: A Systematic Review and Meta-analysis. Clin Infect Dis 2016; 62: 683-694
4) Watanabe H, Saito T, Shinzawa H, et al. Spontaneous elimination of serum hepatitis C virus (HCV) RNA in chronic HCV carriers: a population-based cohort study. J Med Virol 2003; 71: 56-61
9) Kumada H, Chayama K, Rodrigues L Jr, et al. Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis. Hepatology 2015; 62: 1037-1046
10) 持田, 智, 佐久間龍太, 中島 龍, 他. ジェノタイプ1型のC型慢性肝炎およびC型代償性肝硬変患者に対するオムビタスビル/パリタプレビル/リトナビル配合錠の使用成績調査. 肝臓 2021; 62: 690-702
18) Reig M, Mariño Z, Perelló C, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol 2016; 65: 719-726
7) 日本肝臓学会. 「C型肝炎治療ガイドライン第8版」肝炎診療ガイドライン作成委員会編, 2020
26) Piñero F, Mendizabal M, Ridruejo E, et al. Treatment with direct-acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma. Liver Int 2019; 39: 1033-1043
1) 田中純子, 栗栖あけみ, 秋田智之, 他. 厚生労働科学研究費補助金 (肝炎等克服政策研究事業) 令和元年度 分担研究報告書: 肝炎ウイルス感染状況の把握及び肝炎ウイルス排除への方策に資する疫学研究: HBV/HCV持続感染者数の2000年以降の動向-NDBによるreal world解析を含めた推計-. https://mhlw-grants.niph.go.jp/system/files/2019/192161/201921003A_upload/201921003A0023.pdf (2021年11月22日参照
17) Conti F, Buonfiglioli F, Scuteri A, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol 2016; 65: 727-733
25) Ogata F, Kobayashi M, Akuta N, et al. Outcome of All-Oral Direct-Acting Antiviral Regimens on the Rate of Development of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Genotype 1-Related Chronic Liver Disease. Oncology 2017; 93: 92-98
19) Kobayashi M, Suzuki F, Fujiyama S, et al. Sustained virologic response by direct antiviral agents reduces the incidence of hepatocellular carcinoma in patients with HCV infection. J Med Virol 2017; 89: 476-483
16) Yoshida H, Shiratori Y, Moriyama M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med 1999; 131: 174-181
21) Nagaoki Y, Imamura M, Aikata H, et al. The risks of hepatocellular carcinoma development after HCV eradication are similar between patients treated with peg-interferon plus ribavirin and direct-acting antiviral therapy. PLoS One 2017; 12: e0182710
22) Hayashi K, Ishigami M, Ishizu Y, et al. Late relapse of hepatitis C virus in patients with sustained virological response after daclatasvir and asunaprevir therapy. J Viral Hepat 2018; 25: 1446-1451
24) Kanwal F, Kramer J, Asch SM, et al. Risk of Hepatocellular Cancer in HCV Patients Treated With Direct-Acting Antiviral Agents. Gastroenterology 2017; 153: 996-1005.e1
8) Chayama K, Notsumata K, Kurosaki M, et al. Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus-infected patients. Hepatology 2015; 61: 1523-1532
20) Li DK, Ren Y, Fierer DS, et al. The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: An ERCHIVES study. Hepatology 2018; 67: 2244-2253
14) Ikeda K, Saitoh S, Arase Y, et al. Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis. Hepatology 1999; 29: 1124-1130
13) Asahina Y, Tsuchiya K, Tamaki N, et al. Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection. Hepatology 2010; 52: 518-527
28) Sasaki R, Yamasaki K, Abiru S, et al. Serum Wisteria Floribunda Agglutinin-Positive Mac-2 Binding Protein Values Predict the Development of Hepatocellular Carcinoma among Patients with Chronic Hepatitis C after Sustained Virological Response. PLoS One 2015; 10: e0129053
27) Ioannou GN, Green PK, Beste LA, et al. Development of models estimating the risk of hepatocellular carcinoma after antiviral treatment for hepatitis C. J Hepatol 2018; 69: 1088-1098
2) Matsuo J, Mizui M, Okita H, et al. Follow up of the 987 blood donors found with hepatitis C virus infection over 9-18 years. Hepatol Res 2012; 42: 637-647
3) Manns MP, Buti M, Gane E, et al. Hepatitis C virus infection. Nat Rev Dis Primers 2017; 3: 17006
References_xml – reference: 6) 工藤正俊, 泉 並木, 久保正二, 他. 第22回全国原発性肝癌追跡調査報告 (2012～2013) 日本肝癌研究会追跡調査委員会. 肝臓 2021; 62: 251-299
– reference: 5) 国立がん研究センター. がん情報サービス. https://ganjoho.jp/reg_stat/statistics/stat/summary.html (2021年11月22日参照)
– reference: 16) Yoshida H, Shiratori Y, Moriyama M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med 1999; 131: 174-181
– reference: 7) 日本肝臓学会. 「C型肝炎治療ガイドライン第8版」肝炎診療ガイドライン作成委員会編, 2020
– reference: 23) Simmons B, Saleem J, Hill A, et al. Risk of Late Relapse or Reinfection With Hepatitis C Virus After Achieving a Sustained Virological Response: A Systematic Review and Meta-analysis. Clin Infect Dis 2016; 62: 683-694
– reference: 1) 田中純子, 栗栖あけみ, 秋田智之, 他. 厚生労働科学研究費補助金 (肝炎等克服政策研究事業) 令和元年度 分担研究報告書: 肝炎ウイルス感染状況の把握及び肝炎ウイルス排除への方策に資する疫学研究: HBV/HCV持続感染者数の2000年以降の動向-NDBによるreal world解析を含めた推計-. https://mhlw-grants.niph.go.jp/system/files/2019/192161/201921003A_upload/201921003A0023.pdf (2021年11月22日参照)
– reference: 10) 持田, 智, 佐久間龍太, 中島 龍, 他. ジェノタイプ1型のC型慢性肝炎およびC型代償性肝硬変患者に対するオムビタスビル/パリタプレビル/リトナビル配合錠の使用成績調査. 肝臓 2021; 62: 690-702
– reference: 21) Nagaoki Y, Imamura M, Aikata H, et al. The risks of hepatocellular carcinoma development after HCV eradication are similar between patients treated with peg-interferon plus ribavirin and direct-acting antiviral therapy. PLoS One 2017; 12: e0182710
– reference: 26) Piñero F, Mendizabal M, Ridruejo E, et al. Treatment with direct-acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma. Liver Int 2019; 39: 1033-1043
– reference: 4) Watanabe H, Saito T, Shinzawa H, et al. Spontaneous elimination of serum hepatitis C virus (HCV) RNA in chronic HCV carriers: a population-based cohort study. J Med Virol 2003; 71: 56-61
– reference: 8) Chayama K, Notsumata K, Kurosaki M, et al. Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus-infected patients. Hepatology 2015; 61: 1523-1532
– reference: 25) Ogata F, Kobayashi M, Akuta N, et al. Outcome of All-Oral Direct-Acting Antiviral Regimens on the Rate of Development of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Genotype 1-Related Chronic Liver Disease. Oncology 2017; 93: 92-98
– reference: 20) Li DK, Ren Y, Fierer DS, et al. The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: An ERCHIVES study. Hepatology 2018; 67: 2244-2253
– reference: 22) Hayashi K, Ishigami M, Ishizu Y, et al. Late relapse of hepatitis C virus in patients with sustained virological response after daclatasvir and asunaprevir therapy. J Viral Hepat 2018; 25: 1446-1451
– reference: 2) Matsuo J, Mizui M, Okita H, et al. Follow up of the 987 blood donors found with hepatitis C virus infection over 9-18 years. Hepatol Res 2012; 42: 637-647
– reference: 18) Reig M, Mariño Z, Perelló C, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol 2016; 65: 719-726
– reference: 27) Ioannou GN, Green PK, Beste LA, et al. Development of models estimating the risk of hepatocellular carcinoma after antiviral treatment for hepatitis C. J Hepatol 2018; 69: 1088-1098
– reference: 30) De Re V, Tornesello ML, De Zorzi M, et al. Clinical Significance of Polymorphisms in Immune Response Genes in Hepatitis C-Related Hepatocellular Carcinoma. Front Microbiol 2019; 10: 475
– reference: 11) Ioannou GN, Green PK, Berry K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol 2018; 68: 25-32
– reference: 13) Asahina Y, Tsuchiya K, Tamaki N, et al. Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection. Hepatology 2010; 52: 518-527
– reference: 28) Sasaki R, Yamasaki K, Abiru S, et al. Serum Wisteria Floribunda Agglutinin-Positive Mac-2 Binding Protein Values Predict the Development of Hepatocellular Carcinoma among Patients with Chronic Hepatitis C after Sustained Virological Response. PLoS One 2015; 10: e0129053
– reference: 15) Tanaka H, Tsukuma H, Kasahara A, et al. Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C: a retrospective cohort study of 738 patients. Int J Cancer 2000; 87: 741-749
– reference: 17) Conti F, Buonfiglioli F, Scuteri A, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol 2016; 65: 727-733
– reference: 19) Kobayashi M, Suzuki F, Fujiyama S, et al. Sustained virologic response by direct antiviral agents reduces the incidence of hepatocellular carcinoma in patients with HCV infection. J Med Virol 2017; 89: 476-483
– reference: 12) Morgan RL, Baack B, Smith BD, et al. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med 2013; 158: 329-337
– reference: 3) Manns MP, Buti M, Gane E, et al. Hepatitis C virus infection. Nat Rev Dis Primers 2017; 3: 17006
– reference: 9) Kumada H, Chayama K, Rodrigues L Jr, et al. Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis. Hepatology 2015; 62: 1037-1046
– reference: 29) Watanabe T, Tokumoto Y, Joko K, et al. Predictors of hepatocellular carcinoma occurrence after direct-acting antiviral therapy in patients with hepatitis C virus infection. Hepatol Res 2019; 49: 136-146
– reference: 24) Kanwal F, Kramer J, Asch SM, et al. Risk of Hepatocellular Cancer in HCV Patients Treated With Direct-Acting Antiviral Agents. Gastroenterology 2017; 153: 996-1005.e1
– reference: 31) Simili A, Mazzella G, Ravaioli F, et al. Interleukin 28 Polymorphisms and Hepatocellular Carcinoma Development after Direct Acting Antiviral Therapy for Chronic Hepatitis C. J Gastrointestin Liver Dis 2019; 28: 449-456
– reference: 14) Ikeda K, Saitoh S, Arase Y, et al. Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis. Hepatology 1999; 29: 1124-1130
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SubjectTerms C型慢性肝炎
オムビタスビル/パリタプレビル/リトナビル配合錠
サブジェノタイプ1b
肝癌
長期追跡調査
Title サブジェノタイプ1bのC型慢性肝炎及びC型代償性肝硬変患者に対するオムビタスビル/パリタプレビル/リトナビル配合錠の特定使用成績調査：国内臨床試験長期追跡調査
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