Viral Associated Liver Disease Phase III

描述(由申请人提供)： 在这项拟议的研究中，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丙型肝炎病毒，这是导致肝病的主要原因。抗病毒治疗可以消除丙型肝炎病毒，但高度流行的行为、精神和心肺疾病可能会对VA患者的治疗候选和依从性以及治疗成功产生不利影响。因此，目前在退伍军人管理局接受治疗的患者中，只有18%接受过抗丙型肝炎病毒治疗，只有不到4%的患者清除了病毒。即使在相对健康的丙型肝炎患者中，由于根除病毒而改善的临床结果在短期随访研究中也很难量化。VA患者治疗相关结果的改善可能更不显著，因为明显的合并症使这一人群面临更大的肝脏疾病和过早死亡的风险。到目前为止，还没有在大量接受丙型肝炎病毒治疗的患者中进行长期临床结果研究。现在进行这些治疗尤其重要，因为使用蛋白酶抑制剂和聚合酶抑制剂的新一代丙型肝炎疗法可能会在2011年获得FDA的批准，许多VA患者将寻求使用这些药物治疗，尽管目前尚不能获得病毒清除或缺乏这些药物对他们的确切好处。在目前的提案中，我们将研究来自两个独特的丙型肝炎病毒VA患者队列的患者进展为肝硬变、肝硬变失代偿、肝脏相关死亡和所有原因死亡的情况。第一组是1999年至2000年间从退伍军人事务部10家医院招募的2000名丙型肝炎病毒感染者的多点队列。第二个是旧金山退伍军人事务部在过去18年中登记的771名丙型肝炎患者。利用这两个队列，我们将检验接受抗病毒治疗、未能清除病毒或从未接受治疗的退伍军人的长期临床结果的差异。我们还将探索新出现的数据，这些数据表明种族背景不仅与治疗反应相关，这一点已经得到证实，而且还有助于肝硬变的发展风险。这项研究的结果将提供急需的证据，以便更好地为临床医生制定丙型肝炎的治疗决策提供信息。丙型肝炎是一种正在增加退伍军人人数的疾病。 公共卫生相关性： 慢性丙型肝炎病毒感染在美国退伍军人中很流行，估计有20.7万人，即5.4%的退伍军人患者感染了该病毒。这在很大程度上是因为许多退伍军人通过过去的药物使用或在1989年病毒被发现之前感染的受污染的血液产品而接触到病毒。丙型肝炎病毒在发展为晚期肝病之前有一段很长的非活跃期，这可能会危及生命。抗病毒治疗费用昂贵，时间长，会产生不良副作用，而且往往不能清除病毒。一系列不健康的情况会影响治疗资格。这些疾病包括抑郁症、肥胖症、酗酒和活性物质滥用。目前只有18%的丙型肝炎VA患者接受过抗病毒治疗，这是因为他们往往是糟糕的治疗对象。此外，在接受治疗的患者中，只有一小部分人清除了病毒。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，并改善患有丙型肝炎的退伍军人的生活。

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.