Antiviral Therapy in African Americans with HCV

这是一项建议，BIDMC的肝脏中心将在一个多中心合作项目中充当临床试验中心，以检查患有丙型肝炎的非裔美国人对抗病毒治疗的耐药性。在美国，丙型肝炎是一个常见的问题，有近400万人接触到这种病毒。在美国，丙型肝炎病毒是导致肝硬变和肝癌的最常见原因。几乎6%的非裔美国人感染了丙型肝炎病毒，而基于干扰素的抗病毒治疗的应答率只有非西班牙裔白人的50%。这项研究将研究非裔美国人对聚乙二醇干扰素和利巴韦林联合使用的病毒耐药性的机制，并研究可能导致病毒耐药性的因素。其具体目的是：1)确认再生障碍性贫血和白人之间在持续病毒清除方面的差异；2)确定影响抗病毒治疗反应的因素；3)确定治疗期间丙型肝炎病毒动力学对随后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48周的聚乙二醇化干扰素和利巴韦林治疗，然后再随访48周，以确定持续的病毒根除。前处理变量将与病毒清除相关。将收集肝组织和血清样本，用于病毒耐药性的基础研究。这些研究应该有助于确定丙型肝炎再生障碍性贫血的最佳治疗方法。

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.