Division of Infectious Diseases, Massachusetts General Hospital, Boston, USA.
Division of Gastroenterology, Massachusetts General Hospital, Boston MA 02114, USA
BMJ. 2014 Jul 7;348:g3308. doi: 10.1136/bmj.g3308.
Hepatitis C virus (HCV) infection is a substantial health problem worldwide. Most patients infected with HCV remain chronically infected, with an increased risk of cirrhosis and hepatocellular carcinoma. Although they are associated with toxicities and low sustained viral response rates, interferon alfa and ribavirin have been the mainstay of treatment until recently. New direct acting antivirals, specifically designed to inhibit three viral proteins (the NS3/4A protease, the NS5A protein, and the NS5B RNA dependent RNA polymerase) are now becoming available. The NS3/4A inhibitor simeprevir and NS5B inhibitor sofosbuvir have recently been licensed and can reduce the length of antiviral treatment, improve response rates, and allow for interferon-free regimens for some HCV genotypes. Several other newer direct acting antivirals have shown promise in clinical studies and are likely to be licensed soon. These agents seem to facilitate the use of shortened courses of combination interferon-free therapy, which are associated with high (>95%) sustained response rates and relatively few toxicities. These regimens have also been successful in patients who were previously difficult to treat, including those with cirrhosis, HIV coinfection, and those who have undergone liver transplantation. The high cost of these agents may be the biggest challenge to their implementation worldwide.
丙型肝炎病毒(HCV)感染是一个全球性的重大健康问题。大多数感染 HCV 的患者会持续感染,肝硬化和肝细胞癌的风险增加。虽然干扰素α和利巴韦林与毒副作用和低持续病毒应答率相关,但直到最近它们仍是治疗的主要手段。现在,新的直接作用抗病毒药物,专门设计用于抑制三种病毒蛋白(NS3/4A 蛋白酶、NS5A 蛋白和 NS5B RNA 依赖性 RNA 聚合酶),现已上市。NS3/4A 抑制剂simeprevir 和 NS5B 抑制剂索非布韦最近已获得许可,可缩短抗病毒治疗时间、提高应答率,并允许某些 HCV 基因型采用无干扰素治疗方案。其他几种新型直接作用抗病毒药物在临床研究中显示出良好的前景,可能很快也会获得许可。这些药物似乎促进了联合无干扰素治疗疗程的缩短,这些治疗方案与高(>95%)持续应答率和相对较少的毒副作用相关。这些方案在以前难以治疗的患者中也取得了成功,包括肝硬化、HIV 合并感染和肝移植患者。这些药物的高成本可能是在全球范围内实施的最大挑战。