Viral Associated Liver Disease Phase III

描述（由申请人提供）： 在拟议的研究中，我们将检查治疗和未治疗的慢性丙型肝炎病毒（HCV）感染患者的长期临床结果。目前，5.4%的美国退伍军人感染了HCV，这是肝脏疾病的主要原因。抗病毒治疗可以消除HCV，但高度流行的行为，精神和心肺疾病可能会对治疗候选人和依从性以及VA患者的治疗成功产生不利影响。因此，目前在VA接受治疗的患者中只有18%接受过抗HCV治疗，只有不到4%的患者清除了病毒。即使在相对健康的HCV患者中，由于病毒根除而改善的临床结局也难以在短期随访研究中量化。VA患者治疗相关结局的改善可能更不显著，因为显著的合并症使该人群面临更大的肝病和过早死亡风险。到目前为止，还没有在HCV治疗患者的大型队列中进行长期临床结局研究。这些是特别重要的，现在执行，作为新一代的丙型肝炎治疗利用蛋白酶抑制剂和聚合酶抑制剂可能会获得FDA批准在2011年，许多VA患者将寻求与这些药物治疗，虽然确切的好处，他们的病毒清除或缺乏目前还没有。在目前的建议中，我们将研究进展为肝硬化，肝硬化失代偿，肝脏相关的死亡，和所有原因的死亡率之间的患者从两个独特的队列丙型肝炎患者的VA。第一个是1999年至2000年从10家VA医院招募的2000名HCV感染参与者的多地点队列。第二个是在过去18年中招募的771名HCV患者的旧金山弗朗西斯科VA队列。使用这两个队列，我们将研究长期临床结果的差异，退伍军人谁清除HCV与抗病毒治疗，未能清除病毒，或从未接受过治疗。我们还将探讨新出现的数据，这些数据表明种族背景不仅与治疗反应相关，而且还有助于肝硬化发展的风险。这项研究的结果将提供急需的证据，以更好地告知临床医生在作出治疗决定的HCV，一种疾病，正在采取增加收费的退伍军人人口。 公共卫生相关性： 慢性丙型肝炎病毒（HCV）感染在美国退伍军人中流行，估计有207，000或5.4%的VA患者感染了该病毒。这主要是由于许多退伍军人在1989年病毒被发现之前通过过去的药物使用或受污染的血液制品感染而暴露。HCV在发展成晚期肝病之前有很长的非活动期，这可能危及生命。抗病毒治疗是昂贵的，漫长的，导致不良的副作用，往往不能清除病毒。各种不健康状况的组合影响治疗资格。这些包括抑郁症、肥胖症、酗酒和滥用药物。目前只有18%的患有HCV的VA患者接受了抗病毒治疗，因为他们通常是治疗的不良候选人。此外，只有一小部分接受治疗的人清除了病毒。通过准确了解治疗对退伍军人的好处，我们的目标是以最好的方式使用抗病毒药物，从而减少肝病的长期并发症，并改善患有HCV的退伍军人的生活。

DESCRIPTION (provided by applicant): In the proposed study, we will examine long-term clinical outcomes in treated and untreated patients with chronic hepatitis C virus (HCV) infection. Currently, 5.4% of US military veterans are infected with HCV, a major cause of liver disease. Antiviral treatment can eliminate HCV, but highly prevalent behavioral, psychiatric, and cardiopulmonary conditions can adversely impact treatment candidacy and compliance, as well as therapeutic success among VA patients. Thus, only 18% of patients currently in care in the VA have ever received anti-HCV treatment, and fewer than 4% have cleared the virus. Even among relatively healthy HCV patients, improved clinical outcomes due to viral eradication have been difficult to quantitate in short-term follow-up studies. Improved treatment-associated outcomes among VA patients may be even less significant, as marked comorbidities place this population at greater risk for liver disease and for premature death. To date, there have been no long-term clinical outcome studies among large cohorts of HCV-treated patients. These are particularly important to perform now, as a new generation of hepatitis C therapies utilizing protease inhibitors and polymerase inhibitors will likely receive FDA approval in 2011, and many VA patients will seek to be treated with these medications, although precise benefits to them of viral clearance or lack thereof are not currently available. In the current proposal, we will examine the progression to cirrhosis, decompensation of cirrhosis, liver-related death, and all cause mortality among patients from two unique cohorts of HCV patients with the VA. The first is a multisite cohort of 2000 HCV-infected participants recruited between 1999 and 2000 from 10 VA hospitals. The second is a San Francisco VA cohort of 771 HCV patients enrolled over the past 18 years. Using these two cohorts, we will examine differences in long-term clinical outcomes among veterans who cleared HCV with antiviral therapy, failed to clear the virus, or were never treated. We will also explore emerging data that suggest that ethnic background correlates not only with response to treatment, which is well established, but also contributes to risk for cirrhosis development. The results of this study will provide critically needed evidence to better inform clinicians in making treatment decisions for HCV, a disease that is taking an increased toll on the veteran population. PUBLIC HEALTH RELEVANCE: Chronic hepatitis C virus (HCV) infection is epidemic among US veterans, with an estimated 207,000, or 5.4%, of VA patients infected with the virus. This is due largely to the many veterans who were exposed through past drug use or contaminated blood products infected before the virus was identified in 1989. HCV has a long inactive period before it can develop into advanced liver disease, which can be life-threatening. Antiviral therapy is costly, lengthy, causes bad side effects, and often does not clear the virus. A combination of unhealthy conditions influences treatment eligibility. These include depression, obesity, alcoholism and active substance abuse. Only 18% of current VA patients with HCV have received antiviral therapy, due to their often being poor candidates for therapy. Also, only a small proportion of those who are treated clear the virus. By understanding precisely the benefits of treatment to veterans, we aim to use antiviral medications in the best way, and so reduce the long-term complications of liver disease and enhance the lives of veterans with HCV.