The Progression of Hepatitis C Among IDUs

描述（由申请人提供）： 在美国，注射吸毒是丙型肝炎病毒（HCV）传播的主要途径，大多数注射非法药物（IDUs）的人都感染了HCV。HCV感染的主要医学后果是肝衰竭，其发生在纤维化的进行性积累之后，目前只能通过活检可靠地检测到这一过程。通过仔细评估（包括肝活检）随机抽样的210个社区为基础的，HCV感染的注射吸毒者，我们了解到，一些注射吸毒者符合公布的治疗标准，但几乎没有得到治疗，被动的咨询和转诊方法并没有改善治疗的获得。这些发现促使我们研究通过以下方式改善护理的方法：（1）对最需要治疗的注射吸毒者子集进行强化病例管理，（2）通过检测显著肝纤维化的微创标志物来检测该子集。在这项资助中，我们建议使用已经建立的独特资源来扩大我们对注射吸毒者肝纤维化进展的理解。 第一个目的是评估纤维化进展的人口统计学和行为标志物。到本研究开始时，将对最初210名注射吸毒者进行第二次肝活检。将根据性别、年龄、饮酒史和HIV感染状态，通过从第二次活检中减去第一次活检的纤维化评分并除以之间的年数，计算肝纤维化进展率。第二个目标是开发纤维化进展的血液标志物，使用每六个月收集的血清库和活检访视。第三个目的是通过仔细比较具有高纤维化进展率的注射吸毒者子集和具有低进展率的对照组的病毒序列进化和适应性免疫应答来扩展我们对纤维化进展的理解。 总的来说，这项研究将扩大我们对肝纤维化进展的理解，大大提高我们识别HCV感染的注射吸毒者的能力，这些人的疾病风险最大。预计成功的可能性很大，因为这项工作是在宝贵的现有资源基础上进行的，而且将由一组已经显示出必要技能的调查员进行。

DESCRIPTION (provided by applicant): In the United States, injection drug use is the principal route of hepatitis C virus (HCV) transmission and most persons who inject illicit drugs (IDUs) have HCV infection. The chief medical consequence of HCV infection is liver failure, which occurs after a progressive accumulation of fibrosis, a process that currently can only be detected reliably by biopsy. By carefully evaluating (including a liver biopsy) a random sample of 210 community-based, HCV-infected IDUs, we learned that some IDUs met published treatment criteria but almost none had been treated and that passive methods of counseling and referral did not improve treatment acquisition. These findings have led us to investigate methods to improve care delivery by (1) intensive case-management of the subset of IDUs that most need treatment and (2) detection of that subset by testing minimally-invasive markers of significant liver fibrosis. In this grant, we propose using the unique resources already established to expand our understanding of liver fibrosis progression among IDUs. The first aim is to evaluate demographic and behavioral markers of fibrosis progression. By the start of this investigation, a second liver biopsy will have been done on IDUs from the original group of 210. The rate of progression of liver fibrosis will be calculated according to gender, age, alcohol use history, and HIV infection status by subtracting the fibrosis score of the first from the second biopsy and dividing by the years between. The second aim is to develop blood markers of fibrosis progression, using a repository of sera collected every six months and at the biopsy visits. The third aim is to expand our understanding of fibrosis progression by carefully comparing viral sequence evolution and adaptive immune responses for a subset of IDUs with a high fibrosis progression rate and controls with low rates of progression. Collectively, this research will expand our understanding of liver fibrosis progression, substantially improving our ability to identify HCV-infected IDUs who are at greatest risk of disease. A high likelihood of success is anticipated since the work builds on precious existing resources and will be performed by a team of investigators who have already demonstrated the necessary skills.