Future hepatitis C virus treatment: interferon-sparing combinations
Future hepatitis C virus treatment: interferon-sparing combinations
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DOI：
10.1111/j.1478-3231.2010.02383.x
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发表时间：
2011-01-01
影响因子：
6.7
通讯作者：
Gane, Edward
中科院分区：
文献类型：
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作者：
Gane, Edward
据估计，有100万人患有慢性丙型肝炎病毒（HCV）感染。以目前的治疗成功率，到2030年，超过40%的患者将是急性肝炎，预计终末期肝病病例数量将增加两倍。目前的标准治疗是聚乙二醇干扰素加利巴韦林联合治疗24-48周。不幸的是，这与疗效差（HCV GT 1为45%; GT 2为75%，GT 3为65%）和耐受性差有关。许多患者不适合或拒绝目前的治疗感染，因为与这种治疗相关的显著副作用，包括失代偿性肝硬化或严重精神疾病。人们希望开发直接作用的抗病毒药物（DAA）将解决这一巨大的未满足的医疗需求。在聚乙二醇干扰素加利巴韦林的基础上加入蛋白酶抑制剂与HCV GT 1患者的疗效增加和治疗持续时间缩短相关，并可能成为新的标准治疗。然而，三联疗法不适用于非1型HCV感染或有干扰素禁忌症的患者。希望针对HCV复制的不同步骤的多种DAA的组合应该提供无干扰素的治疗方案。目前和计划中的研究将确定哪种组合（蛋白酶、非核苷聚合酶、核苷聚合酶、NS 5A、cyclophyllin B抑制剂）、需要多少DAA和治疗持续时间来优化治愈。最大限度地减少多重耐药的出现也很重要，这将危及未来的再治疗选择。
An estimated million people have chronic hepatitis C virus (HCV) infection. With current treatment success rates, by 2030, more than 40% will be cirrhotic and the number of cases with end-stage liver disease is projected to treble. Current standard-of-care is the combination of pegylated interferon plus ribavirin for 24-48 weeks. Unfortunately this is associated with poor efficacy (45% in HCV GT1; 75% in GT2 and 65% in GT 3) and tolerability. Many patients are either unsuitable for or decline current treatment infection because of the significant side-effects associated with this treatment, including those with decompensated cirrhosis or sever psychiatric illness. It is hoped that the development of direct acting antiviral agents (DAAs) will address this huge unmet medical need. The addition of a protease inhibitor to pegylated interferon plus ribavirin is associated with increase in efficacy and shortened duration of therapy in patients with HCV GT1 and is likely to become the new standard-of-care. However, triple therapy will not be suitable for patients with non-1 HCV infection, or contraindications to interferon. It is hoped that the combination of multiple DAAs which target different steps of HCV replication should provide interferon-free treatment regimen. Current and planned studies will determine which combination (protease, nonnucleoside polymerase, nucleoside polymerase, NS5A, cyclophyllin B inhibitors), how many DAAs and duration of therapy will be required to optimise cure. It will also be important to minimise the emergence of multi-resistance, which would jeopardise future retreatment options.