Ezetimibe併用によるC型慢性肝疾患に対するPeginterferon/Ribavirin療法の成績向上について
C型慢性肝炎に対するPeginterferon alfa-2b（PEG-IFN）/Ribavirin（RBV）療法にコレステロールトランスポーター阻害薬であるEzetimibeを併用する後ろ向き研究を行い，Ezetimibeの有用性につき検討した．PEG-IFN/RBV療法を行い，投与開始から12週目HCV RNA陰性の判定が可能であった1型高ウイルス334例（Ezetimibe併用44例，非併用290例）を対象とした．EVR率は併用群（65.9％）で非併用群（45.2％）より有意（p=0.002）に高かった．多変量解析によるEVR寄与因子にEzetimibe併用が選択された（odds比2.9...
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| Published in | 肝臓 Vol. 51; no. 11; pp. 607 - 614 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本肝臓学会
2010
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| Subjects | |
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| ISSN | 0451-4203 1881-3593 |
| DOI | 10.2957/kanzo.51.607 |
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| Abstract | C型慢性肝炎に対するPeginterferon alfa-2b（PEG-IFN）/Ribavirin（RBV）療法にコレステロールトランスポーター阻害薬であるEzetimibeを併用する後ろ向き研究を行い，Ezetimibeの有用性につき検討した．PEG-IFN/RBV療法を行い，投与開始から12週目HCV RNA陰性の判定が可能であった1型高ウイルス334例（Ezetimibe併用44例，非併用290例）を対象とした．EVR率は併用群（65.9％）で非併用群（45.2％）より有意（p=0.002）に高かった．多変量解析によるEVR寄与因子にEzetimibe併用が選択された（odds比2.993，p=0.004）．累積HCV RNA陰性化率は，併用群で有意に高かった（p=0.0035）．投与前の肝脂肪変性の有無に関わらず併用群では非併用群よりEVR率が高い傾向があった．Ezetimibe併用は，C型慢性肝炎に対するPEG-IFN/RBV療法の治療成績向上に有用である可能性が示唆された． |
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| AbstractList | C型慢性肝炎に対するPeginterferon alfa-2b（PEG-IFN）/Ribavirin（RBV）療法にコレステロールトランスポーター阻害薬であるEzetimibeを併用する後ろ向き研究を行い，Ezetimibeの有用性につき検討した．PEG-IFN/RBV療法を行い，投与開始から12週目HCV RNA陰性の判定が可能であった1型高ウイルス334例（Ezetimibe併用44例，非併用290例）を対象とした．EVR率は併用群（65.9％）で非併用群（45.2％）より有意（p=0.002）に高かった．多変量解析によるEVR寄与因子にEzetimibe併用が選択された（odds比2.993，p=0.004）．累積HCV RNA陰性化率は，併用群で有意に高かった（p=0.0035）．投与前の肝脂肪変性の有無に関わらず併用群では非併用群よりEVR率が高い傾向があった．Ezetimibe併用は，C型慢性肝炎に対するPEG-IFN/RBV療法の治療成績向上に有用である可能性が示唆された． |
| Author | 小坂, 星太郎 須藤, 嘉子 田中, 延善 新, 浩一 神野, 正隆 野ツ俣, 和夫 渡邊, 弘之 宮山, 士朗 真田, 拓 登谷, 大修 松田, 尚登 |
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| References | 2) 野ツ俣和夫, 冨田俊二, 真田, 拓, 他. C型慢性肝炎に対するPeginterferon alfa-2b, Ribavirin併用療法における肝脂肪変性の関与について. 肝臓 2008; 49: 183-191 6) Tanaka Y, Nishida N, Sugiyama N, et al. Genome-wide association of IL28B with Response to pegylated interferon-alfa and ribavirin therapy for chronic hepatitis C. Nat Genet 2009; 41: 1105-1109 23) Syed GH, Amato Y, Siddiqui A. Hepatitis C virus hijacks host lipid metabolism. Trends Endocrinol Metab 2009; 21: 33-40 9) Kamar N, Chatelut E, Manolis E, et al. Ribavirin pharmacokinetics in renal and liver transplant patients: Evidence that it depends on renal function. Am J Kidney Dis 2004; 43: 140-146 10) MuHutchison JC, Everson GT, Gordon SC, et al. Teraprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009; 360: 1827-1831 19) 文屋 学. 脂肪肝合併脂質異常症に対するエゼチミブの有用性. Prog Med 2010; 30: 141-147 17) Zheng S, Hoos L, Cook J. Ezetimibe improves high fat and cholesterol diet-induced non-alcoholic fatty liver disease in mice. Eur J Pharmacol 2008; 584: 118-124 15) Altman SW, Davis HR Jr, Zhu LJ, et al. Niemann-Pick C1 like 1 protein is critical for Intestinal cholesterol absorption. Science 2004; 303: 1201-1204 18) 鈴木伸治. 複合型脂質異常症患者における脂肪肝に対する小腸コレステロールトランスポーター阻害薬エゼチミブの臨床効果―腹部エコーを用いた検討（9月間の中間報告）―. Prog Med 2008; 28: 1769-1775 20) 関耕次朗, 朴 孝憲, 楳村敦詩, 他. 小腸コレステロールトランスポーター阻害剤で腹水が消失し肝予備能の改善を認めた非代償性NASH肝硬変の1例. 肝臓 2009; 50: 532-539 11) Ye J, Wang C, Sumpter R Jr, et al. Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Nat Acad Sci USA 2003; 100: 15865-15870 16) Garcia-Calvo M, Lisnock J, Bull H, et al. The target of ezetimibe is Niemann-Pick C1 like 1 (NPC1L1). Proc Natl Acad Sci USA 2005; 102: 8132-8137 8) Deushi M, Nomura M, Kawakami A, et al. Ezetimibe improves liver steatosis and insulin resistance in obese rat model of metabolic syndrome. FEBS Lett 2007; 581: 5564-5670 21) Enjoji M, Machida K, Kohjima M, et al. NPC1L1 inhibitor ezetimibe is a reliable therapeutic agent for non-obese patients with nonalcoholic fatty liver disease. Lipids Health Dis 2010; 9: 29 5) Akuta N, Suzuki F, Kawamura Y, et al. Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol level. J Hepatol 2007; 46: 403-410 7) Sezaki H, Suzuki F, Acuta N, et al. An open pilot study exploring the efficacy of fluvastatin, pegylated interferon and ribavirin in patients with hepatitis C virus genotype 1b in high vial loads. Intervirology 2009; 52: 43-48 14) Nakamuta M, Yada R, Fujino T, et al. Changes in the expression of cholesterol metabolism-associated genes in HCV-infected liver: A novel target for therapy? Int J Molec Med 2009; 24: 825-828 3) Enomoto N, Sakuma I, Asahina Y, et al. Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N Eng J Med 1996; 334: 77-81 12) Wang C, Gale M Jr, Keller BC, et al. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol Cell 2005; 18: 425-434 4) El-Shamy A, Nagano-Fujii M, Sasae N, et al. Sequence variation in hepatitis C virus nonstructural protein 5A predicts clinical outocome of pegylated interferon/ribabirin combination therapy. Hepatology 2008; 48: 38-47 1) 野ツ俣和夫, 冨田 学, 真田, 拓, 他. ALT持続正常HCVキャリアに対するPeginterferon α2b+Ribavirin併用療法の有用性. 肝臓 2007; 48: 347-352 25) Sakamoto H, Okamoto K, Aoki M, et al. Host sphingolipid biosynthesis as a target for hepatitis C virus therapy. Nat Chem Biol 2005; 1: 333-337 24) Shi ST, Lee KJ, Aizaki H, et al. Hepatitis C virus RNA replication occurs on a detergent-resistant membrane that cofractionates with caveolin-2. J Virol 2003; 77: 4160-4168 22) Yoneda M, Fujita K, Nozaki Y, et al. Efficacy of ezetimibe for the treatment of non-alcoholic steatohepatitis: An open-label, pilot study. Hepatol Res 2010; 19: 19-21 13) Ikeda M, Kato N. Life style-related diseases of the digestive system: cell culture system for the screening of anti-hepatitis C virus (HCV) reagents: suppression of HCV replication by statins and synergistic action with interferon. J Pharmacol Sci 2007; 105: 145-150 |
| References_xml | – reference: 3) Enomoto N, Sakuma I, Asahina Y, et al. Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N Eng J Med 1996; 334: 77-81 – reference: 16) Garcia-Calvo M, Lisnock J, Bull H, et al. The target of ezetimibe is Niemann-Pick C1 like 1 (NPC1L1). Proc Natl Acad Sci USA 2005; 102: 8132-8137 – reference: 25) Sakamoto H, Okamoto K, Aoki M, et al. Host sphingolipid biosynthesis as a target for hepatitis C virus therapy. Nat Chem Biol 2005; 1: 333-337 – reference: 1) 野ツ俣和夫, 冨田 学, 真田, 拓, 他. ALT持続正常HCVキャリアに対するPeginterferon α2b+Ribavirin併用療法の有用性. 肝臓 2007; 48: 347-352 – reference: 10) MuHutchison JC, Everson GT, Gordon SC, et al. Teraprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009; 360: 1827-1831 – reference: 14) Nakamuta M, Yada R, Fujino T, et al. Changes in the expression of cholesterol metabolism-associated genes in HCV-infected liver: A novel target for therapy? Int J Molec Med 2009; 24: 825-828 – reference: 15) Altman SW, Davis HR Jr, Zhu LJ, et al. Niemann-Pick C1 like 1 protein is critical for Intestinal cholesterol absorption. Science 2004; 303: 1201-1204 – reference: 13) Ikeda M, Kato N. Life style-related diseases of the digestive system: cell culture system for the screening of anti-hepatitis C virus (HCV) reagents: suppression of HCV replication by statins and synergistic action with interferon. J Pharmacol Sci 2007; 105: 145-150 – reference: 12) Wang C, Gale M Jr, Keller BC, et al. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol Cell 2005; 18: 425-434 – reference: 23) Syed GH, Amato Y, Siddiqui A. Hepatitis C virus hijacks host lipid metabolism. Trends Endocrinol Metab 2009; 21: 33-40 – reference: 4) El-Shamy A, Nagano-Fujii M, Sasae N, et al. Sequence variation in hepatitis C virus nonstructural protein 5A predicts clinical outocome of pegylated interferon/ribabirin combination therapy. Hepatology 2008; 48: 38-47 – reference: 21) Enjoji M, Machida K, Kohjima M, et al. NPC1L1 inhibitor ezetimibe is a reliable therapeutic agent for non-obese patients with nonalcoholic fatty liver disease. Lipids Health Dis 2010; 9: 29 – reference: 5) Akuta N, Suzuki F, Kawamura Y, et al. Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol level. J Hepatol 2007; 46: 403-410 – reference: 20) 関耕次朗, 朴 孝憲, 楳村敦詩, 他. 小腸コレステロールトランスポーター阻害剤で腹水が消失し肝予備能の改善を認めた非代償性NASH肝硬変の1例. 肝臓 2009; 50: 532-539 – reference: 9) Kamar N, Chatelut E, Manolis E, et al. Ribavirin pharmacokinetics in renal and liver transplant patients: Evidence that it depends on renal function. Am J Kidney Dis 2004; 43: 140-146 – reference: 2) 野ツ俣和夫, 冨田俊二, 真田, 拓, 他. C型慢性肝炎に対するPeginterferon alfa-2b, Ribavirin併用療法における肝脂肪変性の関与について. 肝臓 2008; 49: 183-191 – reference: 6) Tanaka Y, Nishida N, Sugiyama N, et al. Genome-wide association of IL28B with Response to pegylated interferon-alfa and ribavirin therapy for chronic hepatitis C. Nat Genet 2009; 41: 1105-1109 – reference: 17) Zheng S, Hoos L, Cook J. Ezetimibe improves high fat and cholesterol diet-induced non-alcoholic fatty liver disease in mice. Eur J Pharmacol 2008; 584: 118-124 – reference: 19) 文屋 学. 脂肪肝合併脂質異常症に対するエゼチミブの有用性. Prog Med 2010; 30: 141-147 – reference: 7) Sezaki H, Suzuki F, Acuta N, et al. An open pilot study exploring the efficacy of fluvastatin, pegylated interferon and ribavirin in patients with hepatitis C virus genotype 1b in high vial loads. Intervirology 2009; 52: 43-48 – reference: 24) Shi ST, Lee KJ, Aizaki H, et al. Hepatitis C virus RNA replication occurs on a detergent-resistant membrane that cofractionates with caveolin-2. J Virol 2003; 77: 4160-4168 – reference: 22) Yoneda M, Fujita K, Nozaki Y, et al. Efficacy of ezetimibe for the treatment of non-alcoholic steatohepatitis: An open-label, pilot study. Hepatol Res 2010; 19: 19-21 – reference: 11) Ye J, Wang C, Sumpter R Jr, et al. Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Nat Acad Sci USA 2003; 100: 15865-15870 – reference: 8) Deushi M, Nomura M, Kawakami A, et al. Ezetimibe improves liver steatosis and insulin resistance in obese rat model of metabolic syndrome. FEBS Lett 2007; 581: 5564-5670 – reference: 18) 鈴木伸治. 複合型脂質異常症患者における脂肪肝に対する小腸コレステロールトランスポーター阻害薬エゼチミブの臨床効果―腹部エコーを用いた検討（9月間の中間報告）―. Prog Med 2008; 28: 1769-1775 |
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| Snippet | C型慢性肝炎に対するPeginterferon alfa-2b（PEG-IFN）/Ribavirin（RBV）療法にコレステロールトランスポーター阻害薬であるEzetimibeを併用する後ろ向き研究を行い，Ezetimibeの有用性につき検討した．PEG-IFN/RBV療法を行い，投与開始から12週目HCV... |
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| SubjectTerms | C型慢性肝疾患 EVR Ezetimibe Peginterferon/Ribavirin療法 肝脂肪変性 |
| Title | Ezetimibe併用によるC型慢性肝疾患に対するPeginterferon/Ribavirin療法の成績向上について |
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