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慢性丙型肝炎病毒治疗在晚期肝病和肝移植患者中的应用。

Antiviral therapy of chronic hepatitis C in patients with advanced liver disease and after liver transplantation.

机构信息

Department of Medicine I, J.W. Goethe University Hospital, Frankfurt, Germany.

出版信息

Med Microbiol Immunol. 2010 Feb;199(1):1-10. doi: 10.1007/s00430-009-0131-8. Epub 2009 Nov 10.

Abstract

Chronic infection with the hepatitis C virus (HCV) represents one of the major causes for end-stage liver disease worldwide. Although liver transplantation offers an effective treatment, HCV reinfection of the transplanted graft is a critical and almost inevitable complication with major influence on graft- and patient survival. Pre-transplant antiviral therapy in advanced liver disease is limited by poor tolerance and only applicable to mildly decompensated patients but was able to show promising results in patients reaching negative viral load when undergoing transplantation. Prophylactic therapy with HCV antibodies during the anhepatic phase has not been shown to be effective in studies to date. Antiviral therapy after transplantation but before evidence of reinfection, so called pre-emptive treatment, is limited by frequent complications and a high rate of side effects. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic Hepatitis C. With a combination therapy of pegylated interferon and ribavirin, sustained virologic response rates of 25-45% are achieved. However, tolerability is often poor, and the need of dose reduction is frequent. To date, there is no general consensus on modality, timing and dosing of antiviral treatment of HCV in patients with advanced liver disease and after liver transplantation. More randomised, controlled trials are needed. Moreover, upcoming new treatment approaches, e.g. specifically targeted antiviral therapy for hepatitis C (STAT-C) with HCV-specific polymerase and protease inhibitors, may represent a therapeutic alternative.

摘要

慢性丙型肝炎病毒(HCV)感染是全球终末期肝病的主要原因之一。虽然肝移植提供了有效的治疗方法,但移植肝的 HCV 再感染是一个关键且几乎不可避免的并发症,对移植物和患者的生存都有重大影响。晚期肝病患者的肝移植前抗病毒治疗因耐受性差而受到限制,仅适用于轻度失代偿患者,但在接受移植时能使病毒载量阴性的患者获得有前景的结果。迄今为止,研究表明在无肝期使用 HCV 抗体进行预防性治疗并不有效。移植后但在再感染证据之前进行抗病毒治疗,即所谓的抢先治疗,受到频繁并发症和高副作用率的限制。管理的主要方法是在慢性丙型肝炎复发后进行有针对性的抗病毒治疗。采用聚乙二醇干扰素和利巴韦林联合治疗,可达到 25-45%的持续病毒学应答率。然而,耐受性通常较差,需要经常减少剂量。迄今为止,对于晚期肝病患者和肝移植后的 HCV 抗病毒治疗的方式、时机和剂量尚无普遍共识。需要更多的随机对照试验。此外,即将出现的新治疗方法,例如针对丙型肝炎的特定抗病毒治疗(STAT-C)与 HCV 特异性聚合酶和蛋白酶抑制剂,可能代表一种治疗选择。

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