New perspectives for preventing hepatitis C virus liver graft infection.
New perspectives for preventing hepatitis C virus liver graft infection.
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DOI：
10.1016/s1473-3099(16)00120-1
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Baumert TF
中科院分区：
文献类型：
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作者：
Felmlee DJ;Coilly A;Chung RT;Samuel D;Baumert TF
丙型肝炎病毒（HCV）感染是终末期肝病的主要原因，需要肝移植。病毒性肝硬化和肝细胞癌的发病率持续增加，使得肝移植越来越普遍。移植肝脏的感染是普遍的，并增加进展为晚期肝病，其中20-30%在5年内显示肝硬化。虽然慢性HCV感染的治疗已经有了显着改善，尽管仍然存在失败和进入的挑战，但肝移植期间预防移植物感染的治疗选择正在出现。在移植前或移植后直接使用新型直接作用抗病毒（DAA）药物消除循环HCV的最新进展为预防和治疗肝移植感染带来了新的希望。确定DAA的理想方案和使用揭示了这一特殊人群的新治疗模式。作为DAA的补充，进入抑制剂已被证明可以在动物模型中预防肝移植物感染，并在临床试验中延迟移植物感染，这提供了与移植同时使用的前景。我们回顾了与HCV肝移植感染相关的挑战和病理学，强调了DAA治疗时机的当前和未来策略，并讨论了可能与DAA协同抑制移植物感染的进入抑制剂的潜在作用。
Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease that necessitates liver transplantation. The incidence of virus-induced cirrhosis and hepatocellular carcinoma continues to increase, making liver transplantation increasingly common. Infection of the engrafted liver is universal and increases progression to advanced liver disease, with 20–30% displaying cirrhosis within 5 years. While treatments of chronic HCV infection have improved dramatically, albeit with remaining challenges of failure and access, therapeutic options to prevent graft infection during liver transplantation are emerging. Recent developments in directed use of novel direct-acting antiviral (DAA) agents to eliminate circulating HCV prior or following transplantation bring renewed hope for prevention and treatment of liver graft infection. Identifying the ideal regimen and use of DAAs reveals new paradigms of treatment for this special population. Complementing DAAs, entry inhibitors have been shown to prevent liver graft infection in animal models and delay graft infection in clinical trials, providing a perspective to be used concomitant to transplantation. We review the challenges and pathology associated with HCV liver graft infection, highlight current and future strategies of DAA treatment timing, and discuss the potential role of entry inhibitors that might be employed synergistically with DAAs to inhibit graft infection.