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肝移植前后的丙型肝炎治疗

Hepatitis C therapy before and after liver transplantation.

作者信息

Terrault Norah A

机构信息

Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA 94143, USA.

出版信息

Liver Transpl. 2008 Oct;14 Suppl 2:S58-66. doi: 10.1002/lt.21624.

DOI:10.1002/lt.21624
PMID:18825697
Abstract
  1. Pretransplant therapy, using a low-accelerating-dose regimen, is an option for patients with mildly decompensated liver disease and low laboratory Model for End-Stage Liver Disease scores. Achievement of an on-treatment virologic response is the goal of therapy. Preliminary data suggest that up to two-thirds of patients who become hepatitis C virus RNA-negative on treatment will be hepatitis C virus infection-free post-transplantation. 2. Effective prophylactic therapies are not available. Hepatitis C antibody therapy has been ineffective in preventing hepatitis C virus infection in studies to date. 3. Preemptive antiviral therapy started within weeks of transplantation is limited by tolerability, particularly in patients with high Model for End-Stage Liver Disease scores pre-transplantation. Rates of sustained virologic response vary from 8% to 39%. Histological benefits in virologic nonresponders have been demonstrated. 4. Posttransplant antiviral therapy in those with evidence of recurrent disease is the mainstay of management. A combination of pegylated interferon and ribavirin is the treatment of choice, and sustained virologic response is achieved with 48 weeks of treatment in approximately 30% of treated patients. Attainment of early loss of hepatitis C virus RNA is highly predictive of sustained virologic response. Histologic improvements are seen in responders. Survival is prolonged among those achieving a sustained virologic response. 5. Posttransplant antiviral therapy is limited by poor tolerability and the frequent need for dose reductions and/or discontinuation. Immunologic complications, including acute rejection, chronic rejection, and autoimmune-like hepatitis, occur in association with therapy, albeit at low rates. 6. Hepatitis C virus-infected liver transplant recipients represent an important patient population in need of new therapeutics options to prevent patient and graft losses due to recurrent hepatitis C virus disease.
摘要
  1. 对于轻度失代偿性肝病且终末期肝病模型实验室评分较低的患者,采用低加速剂量方案的移植前治疗是一种选择。治疗的目标是实现治疗期间的病毒学应答。初步数据表明,治疗期间丙型肝炎病毒RNA转为阴性的患者中,多达三分之二在移植后将无丙型肝炎病毒感染。2. 目前尚无有效的预防性治疗方法。迄今为止的研究表明,丙型肝炎抗体治疗在预防丙型肝炎病毒感染方面无效。3. 移植后数周内开始的抢先抗病毒治疗受到耐受性的限制,尤其是对于移植前终末期肝病模型评分较高的患者。持续病毒学应答率在8%至39%之间。已证明对病毒学无应答者有组织学益处。4. 对有复发疾病证据的患者进行移植后抗病毒治疗是主要的治疗手段。聚乙二醇干扰素和利巴韦林联合使用是首选治疗方法,约30%接受治疗的患者在48周治疗后可实现持续病毒学应答。早期丙型肝炎病毒RNA转阴对持续病毒学应答具有高度预测性。应答者可见组织学改善。实现持续病毒学应答的患者生存率延长。5. 移植后抗病毒治疗受到耐受性差以及频繁需要降低剂量和/或停药的限制。免疫并发症,包括急性排斥反应、慢性排斥反应和自身免疫样肝炎,与治疗相关,尽管发生率较低。6. 丙型肝炎病毒感染的肝移植受者是一个重要的患者群体,需要新的治疗选择来预防因丙型肝炎病毒疾病复发导致的患者和移植物损失。

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