Optimizing Hepatitis C Therapies and Predicting Liver Disease Outcomes

优化丙型肝炎治疗并预测肝病结果

• 批准号: 9142962
• 负责人: Alexander Monto
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-10-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9142962
• 关键词: Address; Adverse effects; Age; Alcohol consumption; Antiviral Agents; Ascites; Chronic Hepatitis C; Cirrhosis; Clinical; Cohort Studies; Databases; Development; Diabetes Mellitus; Disease; Disease Outcome; Drug Costs; EGF gene; Encephalopathies; Enrollment; Expenditure; Face; Fibrosis; Genes; Genetic; Genetic Polymorphism; Genotype; Guidelines; HCV Cirrhosis; Hemorrhage; Hepatitis C; Hepatitis C Therapy; Hepatitis C virus; Hepatorenal Syndrome; Interferons; Link; Liver diseases; Malignant neoplasm of liver; Measurable; Measures; Medical; Medical center; Methods; Modeling; Monitor; Oral; Outcome; Patients; Pharmaceutical Preparations; Pharmacy facility; Primary carcinoma of the liver cells; Prospective Studies; Race; Regimen; Role; San Francisco; Serum; Services; Severity of illness; Staging; Testing; Veterans; anti-hepatitis C; base; clinical predictors; cohort; cost; genetic predictors; liver biopsy; liver imaging; liver transplantation; novel; prevent; prospective; public health relevance

 DESCRIPTION (provided by applicant): From mid-2014 to mid-2015, the Department of Veterans Affairs spent over $1.2 billion to treat 28,000 of its more than 170,000 hepatitis C virus (HCV) infected patients with new targeted antiviral medications. These combination regimens are a dramatic improvement over prior interferon-based therapies, with 90+% cure rates for hepatitis C with all-oral regimens generally for 3 months, with a reasonable side effect profile. In its current HCV Treatment Guideline, the VA states its commitment to treat all Veterans with HCV who wish to be treated and are suitable for treatment with these medications. It is fair to say that the cost of these drugs, at approximately $40-90,000 per course of treatment for a single patient, is the largest new expenditure that VA Pharmacy and Medical Services will face over the next 3-5 fiscal years. Treatment of all patients is not currently feasible because of the cost of the medications and limited VA treating capacity. We also do not know which patients who are treated will derive the most clinical benefit. Patients with cirrhosis from HCV are currently given the highest priority fo treatment, but whether their liver disease can regress and their rates of complications can be lowered by cure of their hepatitis C is not known. Likely, cirrhosis may be "too late," and hepatitis C cure will not prevent complications of cirrhosis like the need for a liver transplant o the development of hepatocellular carcinoma (HCC). In fact, patients with moderate liver disease without cirrhosis may well derive the most benefit. Some patients may also progress to cirrhosis despite HCV cure, and would benefit from closer monitoring. Such subtle questions require prospective studies to answer, as large databases cannot classify disease so finely. Aim 1 is to establish a prospective cohort of approximately 500 patients with known stage of liver disease who are considered for hepatitis C therapy at the San Francisco VA Medical Center (SFVAMC) over the next two years, with reassessment of liver disease severity by liver imaging (including the novel methods of FIBROSCAN and MR electrography) and serum fibrosis testing at two years after enrollment. Aim 2 is to analyze the most important genes and their polymorphisms, in addition to clinical variables, that have been linked to cirrhosis development, cirrhosis decompensation, and HCC in these patients. We cannot currently predict who will develop complications from HCV, or who will derive measurable clinical benefits from hepatitis C cure, but studying the roles of recently identified genetic polymorphisms and prospectively measuring liver disease before and after therapy should allow us to address both questions.

 描述（由申请人提供）： 从 2014 年中期到 2015 年中期，退伍军人事务部花费了超过 12 亿美元，用新的靶向抗病毒药物治疗了 170,000 多名丙型肝炎病毒 (HCV) 感染患者中的 28,000 名。这些联合治疗方案比以前的干扰素有了显着改善。基于药物的治疗，丙型肝炎治愈率高达 90% 以上，全口服疗法通常持续 3 个月，副作用合理在其当前的 HCV 治疗指南中，VA 承诺治疗所有希望接受治疗且适合使用这些药物治疗的 HCV 退伍军人。公平地说，这些药物的费用约为 40 美元。单个患者每个疗程的费用为 90,000 美元，这是 VA 药房和医疗服务部在未来 3-5 个财政年度将面临的最大的新支出，因为药物成本和 VA 有限，目前不可能对所有患者进行治疗。我们还有治疗能力。不知道哪些接受治疗的患者将获得最大的临床益处，目前最优先接受治疗的是丙型肝炎肝硬化患者，但他们的肝病是否可以通过治愈丙型肝炎来消退以及降低并发症的发生率。目前尚不清楚，肝硬化可能“为时已晚”，丙型肝炎治愈并不能预防肝硬化并发症，例如需要进行肝移植或发展为肝细胞癌（HCC）。尽管 HCV 已被治愈，但一些患者也可能会发展为肝硬化，这些微妙的问题需要前瞻性研究来回答，因为大型数据库无法对疾病进行如此精细的分类。建立一个由约 500 名已知肝病阶段的患者组成的前瞻性队列，这些患者考虑在未来两年内在旧金山退伍军人医疗中心 (SFVAMC) 接受丙型肝炎治疗，并根据肝脏重新评估肝病严重程度入组后两年进行成像（包括 FIBROSCAN 和 MR 电图的新方法）和血清纤维化检测 目标 2 是分析与肝硬化发展、肝硬化相关的最重要的基因及其多态性以及临床变量。我们目前无法预测这些患者中哪些人会出现丙型肝炎并发症，或者哪些人将从丙型肝炎治愈中获得可衡量的临床益处，但可以研究最近发现的遗传因素的作用。多态性和前瞻性测量治疗前后的肝病应该可以让我们解决这两个问题。