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(丙型肝炎病毒)传播的主要途径，大多数注射非法药物的人都感染了丙型肝炎病毒。丙型肝炎病毒感染的主要医学后果是肝功能衰竭，这是在肝纤维化逐渐积累之后发生的，目前只能通过活检可靠地检测到这一过程。通过仔细评估(包括肝脏活检)210名社区感染丙型肝炎病毒的注射吸毒者的随机样本，我们了解到一些注射吸毒者符合已公布的治疗标准，但几乎没有人接受过治疗，被动的咨询和转介方法并没有改善治疗的获得。这些发现促使我们研究通过(1)对最需要治疗的注射吸毒者亚群进行强化病例管理，以及(2)通过检测显著肝纤维化的微创标记物来检测该亚群，从而改善护理提供的方法。在这笔赠款中，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中肝纤维化进展的了解。 第一个目标是评估纤维化进展的人口统计学和行为学标志物。到本次调查开始时，将对最初的210名注射吸毒者进行第二次肝脏活检。肝纤维化的进展率将根据性别、年龄、饮酒史和艾滋病毒感染状况计算出来，方法是从第二次活检中减去第一次肝纤维化评分，然后除以其间的年份。第二个目标是开发纤维化进展的血液标记物，使用每六个月收集一次的血清库和活检访问。第三个目的是通过仔细比较高纤维化进展率的注射吸毒者和低进展率的对照组的病毒序列进化和获得性免疫反应，来扩大我们对纤维化进展的理解。 总而言之，这项研究将扩大我们对肝纤维化进展的理解，显著提高我们识别感染丙型肝炎病毒的注射吸毒者的能力，这些注射吸毒者的疾病风险最高。预计成功的可能性很高，因为这项工作建立在宝贵的现有资源基础上，并将由一组已经证明必要技能的调查人员进行。

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.