Costa MA, Schiff ER
Division of Hepatology, Center for Liver Diseases, University of Miami School of Medicine, 1500 NW 12th Ave., Suite 1101, Miami, FL 33136-1038, USA.
Curr Treat Options Gastroenterol. 1999 Dec;2(6):481-490. doi: 10.1007/s11938-999-0052-z.
End-stage liver disease due to chronic hepatitis C is the leading indication for orthotopic liver transplantation in the United States. Twenty percent to 30% of hepatitis C patients are at increased risk of developing cirrhosis, and 1% to 4% of cirrhotic patients will develop hepatocellular carcinoma. These findings warrant treatment for hepatitis C virus (HCV)-infected patients. Currently, the mainstay in treatment of HCV is the use of recombinant alpha interferon, or its equivalent, in combination with the oral antiviral agent ribavirin. The major goals of therapy are clearance of the virus, achieving a noninfectious state, and halting the necro-inflammatory process that leads to fibrosis and progression to cirrhosis. End of treatment response (ETR) is biochemical and virological remission-- normalization of serum aminotransferase (ALT) and undetectable levels of HCV RNA, at the end of therapy. Sustained virological response (SVR) is defined as the absence of viremia and persistently normal aminotransferase 6 months off treatment, and is the ultimate goal of therapy. Patients who achieve SVR will have significant and persistent histologic improvement. HCV genotype, pretreatment levels of HCV-RNA (viral load), the presence of advanced fibrosis or cirrhosis, gender, and age are independent predictors of response. Ribavirin is teratogenic, therefore, contraception is mandatory for both males and females during and up to 6 months after therapy. Side effects of combination therapy are dose-dependent and most commonly include symptoms of irritability, depression and fatigue, and laboratory evidences of leukopenia, thrombocytopenia, and hemolytic anemia.
在美国,慢性丙型肝炎所致的终末期肝病是原位肝移植的主要指征。20%至30%的丙型肝炎患者发生肝硬化的风险增加,1%至4%的肝硬化患者会发展为肝细胞癌。这些发现表明丙型肝炎病毒(HCV)感染患者需要接受治疗。目前,HCV治疗的主要方法是使用重组α干扰素或其等效物,联合口服抗病毒药物利巴韦林。治疗的主要目标是清除病毒,实现非感染状态,并阻止导致纤维化和进展为肝硬化的坏死性炎症过程。治疗结束反应(ETR)是指治疗结束时生化和病毒学缓解,即血清氨基转移酶(ALT)正常化且HCV RNA水平检测不到。持续病毒学反应(SVR)定义为停止治疗6个月后无病毒血症且氨基转移酶持续正常,是治疗的最终目标。实现SVR的患者将有显著且持续的组织学改善。HCV基因型、HCV-RNA(病毒载量)的治疗前水平、是否存在晚期纤维化或肝硬化、性别和年龄是反应的独立预测因素。利巴韦林具有致畸性,因此,治疗期间及治疗后长达6个月,男性和女性均必须采取避孕措施。联合治疗的副作用与剂量有关,最常见的包括易怒、抑郁和疲劳症状,以及白细胞减少、血小板减少和溶血性贫血的实验室证据。