Viral Associated Liver Disease Phase III

病毒相关性肝病 III 期

基本信息

批准号：
8195995
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
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-10-01 至 2014-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8195995
关键词：
Adverse effects Affect Alcohol consumption Alcoholism Antiviral Agents Antiviral Therapy Ascites Attenuated Behavioral Cardiopulmonary Caring Cessation of life Characteristics Chronic Hepatitis C Cirrhosis Clinic Clinical Comorbidity Computerized Patient Records Consent Data Development Disease Disease Outcome Drug usage Eligibility Determination Enrollment Epidemic Fibrosis Generations Genetic Hemorrhage Hepatic Hepatitis C Hepatitis C Therapy Hepatitis C virus Hepatorenal Syndrome High Prevalence Hospitals Immune Immunity Incidence Infection Inflammation Inflammatory Institutional Review Boards Interferons Kidney Failure Lead Life Liver Liver Cirrhosis Liver Failure Liver Fibrosis Liver diseases Medical Medical center Mental Depression Mental Health Military Personnel Minority Natural History Nature Obesity Outcome Outcome Study Participant Patients Pharmaceutical Preparations Phase Physicians Play Polymerase Population Primary carcinoma of the liver cells Protease Inhibitor Publishing Pulmonary Heart Disease Questionnaires Race Recording of previous events Recruitment Activity Ribavirin Risk Risk Assessment Risk Factors Role San Francisco Severities Staging Substance abuse problem System Therapeutic Time Treatment Factor Treatment outcome Veterans Viral Virus Virus Replication anti-hepatitis C blood product cohort comparison group effective therapy experience follow-up improved information gathering inhibitor/antagonist intrahepatic liver biopsy mortality patient population premature public health relevance racial and ethnic response success treatment response

项目摘要

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.

描述（由申请人提供）：在拟议的研究中，我们将检查接受治疗和未经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 HCV，但高度普遍的行为、精神和心肺疾病可能会对 VA 患者的治疗候选性和依从性以及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% 曾接受过抗 HCV 治疗，只有不到 4% 的患者已经清除了病毒。即使在相对健康的丙肝患者中，由于病毒根除而改善的临床结果也很难在短期随访研究中进行定量。 VA 患者的治疗相关结果的改善可能更不显着，因为明显的合并症使该人群患肝病和过早死亡的风险更大。迄今为止，尚未对大量接受 HCV 治疗的患者进行长期临床结果研究。现在执行这些措施尤其重要，因为利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 批准，并且许多 VA 患者将寻求使用这些药物进行治疗，尽管病毒治疗对他们确实有好处目前尚无许可或缺乏许可。在当前的提案中，我们将检查两个独特的患有 VA 的 HCV 患者队列中患者的肝硬化进展、肝硬化失代偿、肝脏相关死亡和全因死亡率。第一个是 1999 年至 2000 年间从 10 家 VA 医院招募的 2000 名 HCV 感染参与者的多地点队列。第二个是旧金山 VA 队列，该队列由过去 18 年来招募的 771 名 HCV 患者组成。利用这两个队列，我们将研究通过抗病毒治疗清除丙肝病毒、未能清除病毒或从未接受治疗的退伍军人之间长期临床结果的差异。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（这一点已得到证实），而且还与肝硬化发展风险有关。这项研究的结果将提供急需的证据，以便临床医生更好地做出丙型肝炎治疗决策，丙型肝炎是一种对退伍军人造成越来越严重影响的疾病。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 名退伍军人感染该病毒，即 5.4%。这主要是因为在 1989 年病毒被发现之前，许多退伍军人因过去吸毒或受污染的血液制品而受到感染。HCV 在发展为晚期肝病之前有很长一段不活跃期，可能危及生命。抗病毒治疗费用昂贵、时间漫长、会产生严重的副作用，而且通常不能清除病毒。不健康状况的组合会影响治疗资格。这些包括抑郁、肥胖、酗酒和活性物质滥用。目前，只有 18% 的 VA 丙型肝炎患者接受过抗病毒治疗，因为他们通常不太适合接受治疗。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益处，我们的目标是以最佳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肝病毒的退伍军人的生活。