Michielsen P, Ho E, Francque S
Division of Gastroenterology and Hepatology, University Hospital, Faculty of Medicine, University of Antwerp, Antwerp, Belgium.
Minerva Gastroenterol Dietol. 2012 Mar;58(1):65-79.
Infection with the Hepatitis C virus (HCV) affects nearly 200 million people in the world. It is a leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). It is estimated that 25% of HCC worldwide is related to HCV, being the main cause in Western Europe, North America and Japan. HCV can be implicated in the development of HCC in an indirect way through induction of chronic inflammation, or directly by means of viral proteins activating several signaling pathways. For patients with clinically significant hepatic fibrosis there is widespread agreement that antiviral therapy is indicated in order to eliminate the virus. It is generally accepted that sustained virologic response (SVR), i.e. undetectable HCV RNA at 24 weeks after treatment withdrawal, is associated with resolution of liver disease in patients without cirrhosis. In the last decades, results of treatment for chronic hepatitis C have improved substantially. The current standard of care is a combination of pegylated interferon and ribavirin for 24 to 48 weeks, depending on the genotype. In the near future, this standard of care will include addition of directly-acting antivirals. In 2011 two protease inhibitors (boceprevir and telaprevir) have been registered for use in adults with genotype 1 chronic hepatitis C, increasing the SVR rates from less than 50% to about 70% in patients treated with a triple combination. There is limited evidence for the role of interferon-based therapy in primary, secondary and tertiary prophylaxis of HCC in patients with chronic Hepatitis C, as most studies were primarily designed to assess the antiviral effect of treatment and not the long-term impact on the natural history of the disease. Further prospective studies using the more successful emerging treatments of chronic hepatitis C are to be conducted to evaluate the risk of HCC.
丙型肝炎病毒(HCV)感染影响着全球近2亿人。它是慢性肝炎、肝硬化和肝细胞癌(HCC)的主要病因。据估计,全球25%的肝细胞癌与HCV有关,是西欧、北美和日本的主要病因。HCV可通过诱导慢性炎症以间接方式参与肝细胞癌的发生发展,或通过病毒蛋白激活多种信号通路直接参与。对于有临床显著肝纤维化的患者,普遍认为应进行抗病毒治疗以清除病毒。一般认为,持续病毒学应答(SVR),即在停药后24周检测不到HCV RNA,与无肝硬化患者的肝病缓解相关。在过去几十年中,慢性丙型肝炎的治疗结果有了显著改善。目前的标准治疗方案是根据基因型,使用聚乙二醇化干扰素和利巴韦林联合治疗24至48周。在不久的将来,这种标准治疗方案将包括添加直接抗病毒药物。2011年,两种蛋白酶抑制剂(博赛匹韦和特拉匹韦)已获准用于治疗基因型1慢性丙型肝炎的成人患者,三联疗法治疗的患者的SVR率从不到50%提高到了约70%。基于干扰素的治疗在慢性丙型肝炎患者原发性、继发性和三级预防肝细胞癌中的作用证据有限,因为大多数研究主要旨在评估治疗的抗病毒效果,而非对疾病自然史的长期影响。需要进一步开展前瞻性研究,采用更成功的慢性丙型肝炎新出现的治疗方法来评估肝细胞癌的风险。