New antiviral agents and new treatments on the horizon for the management of viral hepatitis

摘要

Transfusion dependant patients are at risk of acquiring transfusiontransmitted viral infections including Hepatitis B virus (HBV) and Hepatitis C (HCV). These infections can lead to cirrhosis and hepatic cancer. Standard treatment, although with improved therapeutic results still exhibits resistance and relapses. New antiviral agents have been developed to further improve results and reduce adverse events. For hepatitis B, along with pegylated interferon a-2a, other drugs that have been approved include lamivudine, adefovir, entecavir, telbivudine and tenofovir, while emtricitabine and clevudine are awaiting FDA approval. Possible combination drug therapy may improve efficacy without engendering resistance. For hepatitis C, standard therapy has been the combination of Peg-IFN/Ribavarin. Genotype 1 of the virus, which is widespread in the USA and Europe, can be resistant to treatment especially with high viral load. Directly acting antiviral agents (DAAs), are being developed. These are: i) HCV NS3 protease inhibitors, such as telaprevir and boceprevir, which are currently approved by the FDA. Several other compounds are in phase I-II development; ii) NS5B polymerase inhibitors, which target HCV replication. These include mericitabine (a nucleoside analogue inhibitor) currently in phase III trials, and nonnucleiside inhibitors; iii) New intreferons such as pgylated interferonl, which are also on trial. Triple therapy using pegylated IFNa/ Ribavarin along with telaprevir or boceprevir are also under trial. ? 输血依赖型患者面临输血传播病毒感染的风险，包括乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）。 这些感染可导致肝硬化和肝癌。 标准治疗，尽管具有改善的治疗效果，但是仍然表现出抗病性和复发性 已研发出新的抗病毒药物，进一步完善结果和降低不良事件。 关于乙型肝炎，和聚乙二醇化干扰素a-2a一起，其他已获批准的药物包括拉米夫定、阿德福韦、恩替卡韦、替比夫定以及替诺福韦，恩曲他滨和克来夫定仍等待美国食品和药物管理局的批准。 可能的药物联合疗法可能会提高疗效，而不会产生抗病性。 关于丙型肝炎，标准疗法为聚乙二醇化干扰素/利巴韦林的联合治疗。 1号基因型丙型肝炎病毒在美国和欧洲广泛传播，可以抵抗治疗，特别是高病毒载荷。 正在研发直接作用的抗病毒药物（DAA）。 它们是： 1）HCV NS3蛋白酶抑制剂，如Telaprevir 和Boceprevir，目前它们已获得被美国食品和药物管理局批准。 其他几种化合物也正在进行第一阶段或第二阶段的研发；2）NS5B 聚合酶抑制剂，其针对丙型肝炎病毒的复制。 它们包括目前正在进行第二阶段试验的Mericitabine （一种核苷聚合酶抑制剂）以及单核苷抑制剂；3）新的干扰素，如加入聚乙二醇的干扰素正在试验之中。 使用加入聚乙二醇的IFNa/ 利巴韦林和Telaprevir 或Boceprevir的三联疗法也正在试验之中。