Asselah Tarik, Benhamou Yves, Marcellin Patrick
INSERM, U773, Centre de Recherche Bichat-Beaujon CRB3, Service d'hépatologie, Hôpital Beaujon, Clichy, France.
Liver Int. 2009 Jan;29 Suppl 1:57-67. doi: 10.1111/j.1478-3231.2008.01928.x.
Chronic hepatitis C is among the leading causes of chronic liver disease worldwide, with approximately 170 million people infected. The severity of disease varies from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma. Recently,advances have been made, with the combination of pegylated interferon (PEG-IFN) and ribavirin leading to a sustained virological response (SVR) in approximately 55% of cases. In genotypes 2 or 3, SVR rates reach 80%; in genotype 1 SVR rates is 50%. Furthermore, SVR appears to be long lasting, associated probably with a reduction in the risk of cirrhosis and hepatocellular carcinoma. Despite this progress, treatment failure still occurs in about half of the patients. Furthermore, therapy results in several side effects and high costs. These limitations have led to important development of novel compounds under the name of specifically targeted antiviral therapy for HCV (STAT-C). Also, considering side effects and treatment cost, prediction of virological non-response is mandatory. The management of chronic hepatitis C must include better knowledge of viral cycle and mechanisms of non response. The development of new molecules such as HCV enzyme inhibitors is ongoing. The aim of this review is to summarize results obtained with STATC: protease and polymerase inhibitors.
慢性丙型肝炎是全球慢性肝病的主要病因之一，约有1.7亿人感染。疾病的严重程度从无症状慢性感染到肝硬化和肝细胞癌不等。最近取得了进展，聚乙二醇化干扰素（PEG-IFN）和利巴韦林联合使用可使约55%的病例获得持续病毒学应答（SVR）。在基因2型或3型中，SVR率达到80%；在基因1型中，SVR率为50%。此外，SVR似乎是持久的，可能与肝硬化和肝细胞癌风险降低有关。尽管取得了这一进展，但仍有约一半的患者治疗失败。此外，治疗会导致多种副作用和高昂费用。这些局限性促使了以针对丙型肝炎的特异性靶向抗病毒治疗（STAT-C）为名的新型化合物的重要发展。此外，考虑到副作用和治疗成本，预测病毒学无应答是必不可少的。慢性丙型肝炎的管理必须包括对病毒周期和无应答机制的更好了解。诸如丙型肝炎病毒酶抑制剂等新分子的研发正在进行中。本综述的目的是总结使用STAT-C（蛋白酶和聚合酶抑制剂）所取得的结果。
