HEPATITIS C ANTIVIRAL LONG-TERM TREATMENT TO PREVENT CIRRHOSIS (HALT-C) TRIAL

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。丙型肝炎是美国慢性肝病最常见的原因之一。大约有300-400万美国人患有慢性丙型肝炎。其中，每年估计有8,000-10,000人死于肝硬变或肝癌。目前，唯一被批准的慢性丙型肝炎治疗方法是单独使用干扰素或与利巴韦林联合使用。虽然联合治疗与更高的应答率相关，但只有不到50%的丙型肝炎患者会有持续的应答。最近的研究发现，一些在干扰素或联合治疗期间没有反应(清除丙型肝炎病毒)的患者的肝病得到了改善，重复肝活检证明炎症减少了。也有报告表明，干扰素治疗可能会降低丙型肝炎引起的肝硬变患者罹患肝癌的风险。这项研究的目的是确定长期的干扰素治疗是否可以防止对以前的治疗无效的丙型肝炎患者的纤维化(疤痕形成)的进展和肝硬变、肝衰竭和肝癌的发展。这是一项由美国国立卫生研究院(NIH)赞助的多中心临床试验。密歇根大学是被选中参与这项试验的9个中心之一。约1000名丙型肝炎患者(其中120人来自密歇根大学)将参加这项试验，这些患者对以前的干扰素治疗无效的丙型肝炎和肝活检中的3级或更多纤维化。所有患者都将接受聚乙二醇化干扰素和利巴韦林联合治疗24周。聚乙二醇化干扰素是一种长效干扰素制剂，初步临床试验表明，它在诱导反应方面比标准干扰素制剂更有效。重新治疗的目的是为患者提供目前可用的最好的治疗。未能清除病毒的患者随后将被随机分组，继续接受聚乙二醇化干扰素治疗或不治疗3.5年。这两组患者都将受到密切监测，并将在第二年和第四年结束时重复进行肝脏活检，以确定长期服用聚乙二醇化干扰素在预防肝纤维化、肝硬化、肝功能衰竭和肝癌方面是否安全有效。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hepatitis C is one of the most common causes of chronic liver disease in the United States. Approximately 3-4 million Americans have chronic hepatitis C infection. Of these, 8,000-10,000 are estimated to die from cirrhosis or liver cancer each year. Currently, the only approved treatment for chronic hepatitis C is interferon alone or in combination with ribavirin. Although combination therapy is associated with a higher response rate, less than 50% hepatitis C patients will have a sustained response. Recent studies found that some patients who fail to respond (clear the hepatitis C virus) during treatment with interferon or combination therapy have improvement in liver disease demonstrated by decreased inflammation on repeat liver biopsies. There have also been reports indicating that interferon treatment may decrease the risks of developing liver cancer in patients with cirrhosis due to hepatitis C. The purpose of this study is to determine if long-term interferon treatment will prevent progression of fibrosis (scarring) and development of liver cirrhosis, liver failure and liver cancer in hepatitis C patients who failed to respond to previous therapy. This is a multi-center clinical trial sponsored by the National Institutes of Health (NIH). The University of Michigan is 1 of 9 centers selected to participate in this trial. Approximately 1000 patients (120 from the University of Michigan) with hepatitis C and stage 3 or more fibrosis on liver biopsy, who failed to respond to previous interferon therapy will be enrolled in this trial. All patients will be re-treated with a combination of pegylated interferon and ribavirin for 24 weeks. Pegylated interferon is a long-acting preparation of interferon, which has been shown in preliminary clinical trials to be more effective in inducing a response than standard preparations of interferon. The purpose of the re-treatment is to provide patients with the best treatment currently available. Patients who fail to clear the virus will then be randomized to continue treatment with pegylated interferon alone or no treatment for another 3.5 years. Both groups of patients will be closely monitored and liver biopsies will be repeated at the end of years 2 and 4 to determine if long-term pegylated interferon is safe and effective in preventing progression of liver fibrosis, cirrhosis, liver failure and liver cancer.