Antiviral Therapy in African Americans with HCV

这是BIDMC肝脏中心作为多中心合作项目中的临床试验中心的一项提案，旨在检查患有丙型肝炎的非洲裔美国人对抗病毒治疗的耐药性。HCV是美国的一个常见问题，有近400万人暴露于该病毒。HCV是美国肝硬化和肝癌的最常见原因。几乎6%的非洲裔美国人患有HCV，并且对基于干扰素的抗病毒治疗的反应仅为非HI西班牙白人的50%。本研究将研究非裔美国人对PEG-干扰素联合利巴韦林的病毒耐药机制，并研究可能导致病毒耐药的因素。具体目的是：1）确认AA和白人之间持续病毒清除存在差异; 2）确定影响抗病毒治疗应答的因素; 3）确定治疗期间HCV病毒动力学对后续持续病毒清除的作用; 4）确定决定病毒清除的病毒学、免疫学和宿主遗传因素。大约400名患者将接受PEG-IFN和利巴韦林治疗48周，然后再随访48周，以确定持续的病毒根除。治疗前变量将与病毒清除率相关。将采集肝组织和血清标本用于病毒耐药性的基础研究。这些研究应该有助于确定AA与HCV的最佳治疗方法。

This is a proposal for the Liver Center at BIDMC to act as a clinical trials center in a multicenter collaborative program to examine resistance to antiviral therapy in African Americans with hepatitis C. HCV is a common problem in the US with almost 4 million individuals exposed to the virus. HCV is the commonest cause of cirrhosis and liver cancer in the US. Almost 6% of African Americans have HCV and there response to Interferon based antiviral therapy is only 50% that of non-HIspanic whites. This study will examine the mechanism of viral resistance in African Americans to PEG-Interferon combined with ribavirin and examine the factors potentially responsible for viral resistance. The specific Aims are to 1) Confirm that there is a difference in sustained viral clearance between AA and whites; 2) Identify factors that effect response to antiviral therapy; 3) determine the role of HCV viral kinetics during therapy on subsequent sustained viral clearance; 4) identify virological, immunological-and host genetic factors that determine viral clearance. Approximately 400 patients will be treated with PEG-IFN and ribavirin for 48 weeks and then followed for a further 48 weeks to determine sustained viral eradication. Pretreatment variables will be correlated with viral clearance. Specimens of liver tissue and serum will be collected for basic studies on viral resistance. These studies should help determine the best therapy for AA with HCV.