C型慢性肝炎に対するasunaprevir/daclatasvir併用療法著効後に発症した肝細胞癌の1例
症例は75歳男性．61歳時，遺伝子型1b高ウイルス量C型慢性肝炎の診断でIFNα-2b+ribavirin（RBV）併用療法を，69歳時，Peg-IFNα-2b+RBV併用療法を受けるも無効であった．患者宿主因子の検索で，インターフェロン（IFN）λ3（IFNL3）がTT, IFNλ4（IFNL4）がTT/Δ Gと乖離を示した．70歳時，asunaprevirとdaclatasvir併用の臨床試験に参加し，24週間の治療で著効が得られた．75歳時，肝S8に9 mmの肝細胞癌を認め，経皮的ラジオ波焼灼療法が行われた．IFN後の著効例では，特に，男性，高齢者や肝線維化進展例で肝発癌のリスクが高いこ...
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| Published in | 肝臓 Vol. 56; no. 7; pp. 348 - 355 |
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| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本肝臓学会
2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0451-4203 1881-3593 |
| DOI | 10.2957/kanzo.56.348 |
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| Abstract | 症例は75歳男性．61歳時，遺伝子型1b高ウイルス量C型慢性肝炎の診断でIFNα-2b+ribavirin（RBV）併用療法を，69歳時，Peg-IFNα-2b+RBV併用療法を受けるも無効であった．患者宿主因子の検索で，インターフェロン（IFN）λ3（IFNL3）がTT, IFNλ4（IFNL4）がTT/Δ Gと乖離を示した．70歳時，asunaprevirとdaclatasvir併用の臨床試験に参加し，24週間の治療で著効が得られた．75歳時，肝S8に9 mmの肝細胞癌を認め，経皮的ラジオ波焼灼療法が行われた．IFN後の著効例では，特に，男性，高齢者や肝線維化進展例で肝発癌のリスクが高いことが知られており，著効後も長期に渡る経過観察が必要とされている．IFN-freeの治療では，高齢者や肝硬変例においても高率に著効が得られるため，著効後の肝発癌について特に注意を要すると考えられ報告する． |
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| AbstractList | 症例は75歳男性．61歳時，遺伝子型1b高ウイルス量C型慢性肝炎の診断でIFNα-2b+ribavirin（RBV）併用療法を，69歳時，Peg-IFNα-2b+RBV併用療法を受けるも無効であった．患者宿主因子の検索で，インターフェロン（IFN）λ3（IFNL3）がTT, IFNλ4（IFNL4）がTT/Δ Gと乖離を示した．70歳時，asunaprevirとdaclatasvir併用の臨床試験に参加し，24週間の治療で著効が得られた．75歳時，肝S8に9 mmの肝細胞癌を認め，経皮的ラジオ波焼灼療法が行われた．IFN後の著効例では，特に，男性，高齢者や肝線維化進展例で肝発癌のリスクが高いことが知られており，著効後も長期に渡る経過観察が必要とされている．IFN-freeの治療では，高齢者や肝硬変例においても高率に著効が得られるため，著効後の肝発癌について特に注意を要すると考えられ報告する． |
| Author | 豊田, 成司 小関, 至 荒川, 智宏 桑田, 靖昭 髭, 修平 中島, 知明 後藤田, 裕子 狩野, 吉康 佐藤, 隆啓 山口, 将功 岩口, 佳史 木村, 睦海 大村, 卓味 |
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| References | 2) Takaoka A, Taniguchi T. New aspects of IFN-alpha/beta signalling in immunity, oncogenesis and bone metabolism. Cancer Sci 2003; 94: 405-411 19) Karino Y, Ozeki I, Hige S, et al. Analysis of the liver function and hepatic reserve improvement effects, and liver carcinogenesis restraint effect of the daclatasvir plus asnaprevir combination therapy. AASLD 2014; abstract #1012 3) Damdinsuren B, Nagano H, Wada H, et al. Stronger growth-inhibitory effect of interferon (IFN)-beta compared to IFN-alpha is mediated by IFN signaling pathway in hepatocellular carcinoma cells. Int J Oncol 2007; 30: 201-208 20) Kuno A, Ikehara Y, Tanaka Y, et al. A serum "sweet-doughnut" 272 protein facilitates fibrosis evaluation and therapy assessment in patients 273 with viral hepatitis. . Sci Rep 2013; 3: 1065 11) 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 13) Nozawa Y, Umemura T, Katsuyama Y, et al. Genetic polymorphism in IFNL4 and response to pegylated interferon-α and ribavirin in Japanese chronic hepatitis C patients. Tissue Antigens 2014; 83: 45-48 15) Mizokami M, Takehara T, Yokosuka O, et al. 100% SVR12 in Japanese patients with chronic genotype 1 hepatitis C virus infection receiving Ledipasvir/Sofosbuvir fixed-dose combination for 12 weeks: results from a multicenter phase 3 study. AASLD 2014; abstract #1929 16) Osaki Y, Ueda Y, Marusawa Y, et al. Decrease in alpha-fetoprotein levels predicts reduced incidence of hepatocellular carcinoma in patients with hepatitis C virus infection receiving interferon therapy: a single center study. J Gastroenterol 2012; 47: 444-451 6) 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 7) Okanoue T, Itoh Y, Minami M, et al. Interferon therapy lowers the rate of progression to hepatocellular carcinoma in chronic hepatitis C but not significantly in advanced stage: a retrospective study in 1,148 patients. Viral Hepatitis Therapy Study Group. J Hepatol 1999; 30: 653-659 9) Watanabe S, Enomoto N, Koike K, et al. Cancer preventive effect of pegylated interferon α-2b plus ribavirin in a real-life clinical setting in Japan. PERFECT interim analysis. Hepatol Res 2011; 41: 955-964 12) Prokunina-Olsson L, Muchmore B, Tang W, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 2013; 45: 164-171 10) Ogawa E, Furusyo N, Kajiwara E, et al. Efficacy of pegylated interferon α-2b and ribavirin treatment on the risk of hepatocellular carcinoma in patients with chronic hepatitis C: a prospective multicenter study. J Hepatol 2013; 58: 495-501 21) Masuzaki R, Tateishi R, Yoshida H, et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology 2009; 49: 1954-1961 4) Nishiguchi S, Kuroki T, Nakatani S, et al. Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 1995; 346: 1051-1055 1) Kumada H, Suzuki Y, Ikeda K, et al. Daclatasvir plus asnaprevir for chronic HCV genotype 1b infection. Hepatology 2014; 59: 2083-2091 8) Ikeda K, Saitoh S, Arase Y, et al. Effect of interferon therapy on hepatocellular carcinoma 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 14) Miyamura T, Kanda T, Nakamoto S, et al. IFNL4 ss469415590 variant is associated with treatment response in Japanese HCV genotype 1 infected individuals treated with IFN-including regimens. Int J Hepatol 2014; 2014: 723868 doi: 10.1155/2014/723868 18) Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibro- sis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatology 2007; 46: 32-36 5) Kasahara A, Hayashi N, Mochizuki K, et al. Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group. Hepatology 1998; 27: 1394-1402 17) Oze T, Hiramatsu N, Yakushijin T, et al. Post-treatment levels of α-fetoprotein predict incidence of hepatocellular carcinoma after interferon therapy. Clinical Gastroenterology and Hepatology 2014; 12: 1186-1195 |
| References_xml | – reference: 1) Kumada H, Suzuki Y, Ikeda K, et al. Daclatasvir plus asnaprevir for chronic HCV genotype 1b infection. Hepatology 2014; 59: 2083-2091 – reference: 2) Takaoka A, Taniguchi T. New aspects of IFN-alpha/beta signalling in immunity, oncogenesis and bone metabolism. Cancer Sci 2003; 94: 405-411 – reference: 12) Prokunina-Olsson L, Muchmore B, Tang W, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 2013; 45: 164-171 – reference: 9) Watanabe S, Enomoto N, Koike K, et al. Cancer preventive effect of pegylated interferon α-2b plus ribavirin in a real-life clinical setting in Japan. PERFECT interim analysis. Hepatol Res 2011; 41: 955-964 – reference: 11) 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: 14) Miyamura T, Kanda T, Nakamoto S, et al. IFNL4 ss469415590 variant is associated with treatment response in Japanese HCV genotype 1 infected individuals treated with IFN-including regimens. Int J Hepatol 2014; 2014: 723868 doi: 10.1155/2014/723868 – reference: 5) Kasahara A, Hayashi N, Mochizuki K, et al. Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group. Hepatology 1998; 27: 1394-1402 – reference: 21) Masuzaki R, Tateishi R, Yoshida H, et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology 2009; 49: 1954-1961 – reference: 15) Mizokami M, Takehara T, Yokosuka O, et al. 100% SVR12 in Japanese patients with chronic genotype 1 hepatitis C virus infection receiving Ledipasvir/Sofosbuvir fixed-dose combination for 12 weeks: results from a multicenter phase 3 study. AASLD 2014; abstract #1929 – reference: 18) Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibro- sis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatology 2007; 46: 32-36 – reference: 19) Karino Y, Ozeki I, Hige S, et al. Analysis of the liver function and hepatic reserve improvement effects, and liver carcinogenesis restraint effect of the daclatasvir plus asnaprevir combination therapy. AASLD 2014; abstract #1012 – reference: 16) Osaki Y, Ueda Y, Marusawa Y, et al. Decrease in alpha-fetoprotein levels predicts reduced incidence of hepatocellular carcinoma in patients with hepatitis C virus infection receiving interferon therapy: a single center study. J Gastroenterol 2012; 47: 444-451 – reference: 13) Nozawa Y, Umemura T, Katsuyama Y, et al. Genetic polymorphism in IFNL4 and response to pegylated interferon-α and ribavirin in Japanese chronic hepatitis C patients. Tissue Antigens 2014; 83: 45-48 – reference: 4) Nishiguchi S, Kuroki T, Nakatani S, et al. Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 1995; 346: 1051-1055 – reference: 7) Okanoue T, Itoh Y, Minami M, et al. Interferon therapy lowers the rate of progression to hepatocellular carcinoma in chronic hepatitis C but not significantly in advanced stage: a retrospective study in 1,148 patients. Viral Hepatitis Therapy Study Group. J Hepatol 1999; 30: 653-659 – reference: 8) Ikeda K, Saitoh S, Arase Y, et al. Effect of interferon therapy on hepatocellular carcinoma 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 – reference: 3) Damdinsuren B, Nagano H, Wada H, et al. Stronger growth-inhibitory effect of interferon (IFN)-beta compared to IFN-alpha is mediated by IFN signaling pathway in hepatocellular carcinoma cells. Int J Oncol 2007; 30: 201-208 – reference: 6) 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: 20) Kuno A, Ikehara Y, Tanaka Y, et al. A serum "sweet-doughnut" 272 protein facilitates fibrosis evaluation and therapy assessment in patients 273 with viral hepatitis. . Sci Rep 2013; 3: 1065 – reference: 17) Oze T, Hiramatsu N, Yakushijin T, et al. Post-treatment levels of α-fetoprotein predict incidence of hepatocellular carcinoma after interferon therapy. Clinical Gastroenterology and Hepatology 2014; 12: 1186-1195 – reference: 10) Ogawa E, Furusyo N, Kajiwara E, et al. Efficacy of pegylated interferon α-2b and ribavirin treatment on the risk of hepatocellular carcinoma in patients with chronic hepatitis C: a prospective multicenter study. J Hepatol 2013; 58: 495-501 |
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| SubjectTerms | asunaprevir C型慢性肝疾患 daclatasvir 肝発癌 |
| Title | C型慢性肝炎に対するasunaprevir/daclatasvir併用療法著効後に発症した肝細胞癌の1例 |
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