REDUCTION OF HCV RECURRANCE AFTER LIVER TRANSPLANTATION

背景：丙型肝炎病毒（HCV）继发的终末期肝病 感染是原位肝移植的主要适应症 (OLT)在美国 HCV感染的复发率几乎 普遍，10例HCV感染受者经历了早期移植 继发于复发性HCV疾病的损失或死亡。 国家 糖尿病、消化和肾脏疾病研究所肝脏 移植数据库（LTD）最近表明， 通过HCV RNA测量的奥尔特病毒载量可预测患者和 移植物存活率目前尚不清楚降低OLT前病毒载量是否会 提高病毒学复发率或患者或移植物存活率 在HCV感染的接受者中奥尔特。 目的：为设计一个多中心， 双盲、随机、对照试验， α（IFN-α）和利巴韦林将由国家 糖尿病、消化和肾脏疾病研究所肝脏 移植数据库与另外三个肝脏 移植中心。 为了设计这样一项研究， 的规划补助金建议是：1）建立最佳的研究规模 和持续时间（功效计算、分层策略） 目前HCV感染患者的病毒学特征 在参与中心等待肝移植，以及2） 确定两种形式的IFN-α的耐受性和疗效， 病毒唑治疗继发于HCV的终末期肝病患者。 方法：在参与中心等待奥尔特的HCV感染患者 (the马约诊所和基金会，西奈山医疗中心，纽约， 加州大学旧金山弗朗西斯科 匹兹堡大学、内布拉斯加大学和贝勒大学医学院 中心）将被邀请参加研究。 60名与会者 将随机接受单独的非聚乙二醇化IFN-α、非聚乙二醇化IFN-α和非聚乙二醇化IFN-α。 聚乙二醇化IFN-α +利巴韦林或聚乙二醇化IFN-α +利巴韦林。 统计分析将由公共研究生院进行 匹兹堡大学的健康。 意义：规划阶段的结果将有助于 多中心双盲、随机、 对照试验包括IFN-α和利巴韦林，以确定 降低OLT前HCV RNA滴度对移植后结果的影响， 包括HCV复发。

Background: End-stage liver disease secondary to hepatitis C virus (HCV) infection is the leading indication for orthotopic liver transplantation (OLT) in the United States. Recurrence of HCV infection is nearly universal, with 10 of HCV-infected recipients experiencing early graft loss or death secondary to recurrent HCV disease. The National Institutes of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database (LTD) has recently demonstrated that the pre- OLT viral load, as measured by HCV RNA, is predictive of patient and graft survival. It is not known whether lowering pre-OLT viral load will improve the rate of virological recurrence, or patient or graft survival following OLT in HCV-infected recipients. Aims: A planning grant is proposed for the design of a multi-center, double-blind, randomized, controlled trial incorporating interferon- alpha (IFN-alpha) and ribavirin to be conducted by the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database in conjunction with three additional Liver Transplant Centers. In order to design such a study, the specific aims of the planning grant proposal are: 1) to establish optimal study size and duration (power calculations, stratification strategy) through the virological characterization of the HCV-infected patients currently awaiting liver transplantation at the participating centers and 2) to determine the tolerability and efficacy of two forms of IFN-alpha and ribavirin in patients with end-stage liver disease secondary to HCV. Methods: HCV-infected patients awaiting OLT at the participating centers (the Mayo Clinic and Foundation, Mount Sinai Medical Center, New York, the University of California San Francisco, the University of Pittsburgh, the University of Nebraska and Baylor University Medical Center) will be invited to participate in the study. Sixty participants will be randomized to receive either non-pegylated IFN-alpha alone, non- pegylated IFN-alpha + ribavirin or pegylated IFN-alpha + ribavirin. Statistical analysis will be performed by the Graduate School of Public Health at the University of Pittsburgh. Significance: The results of the planning phase will facilitate the design and coordination of the multi-center double-blind, randomized, controlled trial incorporating IFN-alpha and ribavirin to determine the effect of lowering pre-OLT HCV RNA titers on posttransplant outcomes, including HCV recurrence.