REDUCTION OF HCV RECURRANCE AFTER LIVER TRANSPLANTATION

减少肝移植后 HCV 复发

• 批准号: 2718450
• 负责人: MICHAEL R CHARLTON
• 金额: $ 5.36万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2718450
• 关键词: clinical research; clinical trials; combination therapy; hepatitis C; hepatitis C virus; human subject; human therapy evaluation; interferon alpha; liver disorder chemotherapy; liver transplantation; microorganism disease chemotherapy; polyethylene glycols; relapse /recurrence; ribavirin; virus RNA

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.

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感染复发率接近 普遍存在，10 名 HCV 感染者经历了早期移植 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）最近证明，预移植 通过 HCV RNA 测量的 OLT 病毒载量可预测患者和 移植物存活。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 HCV 感染者接受 OLT 治疗后。 目标： 提议为设计一个多中心、 纳入干扰素的双盲、随机、对照试验 α（IFN-α）和利巴韦林将由国家实验室进行 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相结合 移植中心。 为了设计这样的研究，具体目标 规划拨款提案包括： 1) 确定最佳研究规模 和持续时间（功率计算、分层策略） 目前HCV感染者的病毒学特征 在参与中心等待肝移植并且 2) 确定两种形式的 IFN-α 的耐受性和功效 利巴韦林治疗继发于 HCV 的终末期肝病患者。 方法：在参与中心等待 OLT 的 HCV 感染患者 （梅奥诊所和基金会，西奈山医疗中心，纽约， 加州大学旧金山分校 匹兹堡大学、内布拉斯加大学和贝勒大学医学院 中心）将被邀请参加这项研究。 六十名参加者 将被随机分配接受单独的非聚乙二醇化 IFN-α 治疗、非聚乙二醇化 IFN-α 治疗 聚乙二醇化 IFN-α + 利巴韦林或聚乙二醇化 IFN-α + 利巴韦林。 统计分析将由公立研究生院进行 匹兹堡大学健康学院。 意义：规划阶段的结果将有助于 多中心双盲、随机、 结合 IFN-α 和利巴韦林的对照试验以确定 降低 OLT 前 HCV RNA 滴度对移植后结果的影响， 包括丙型肝炎病毒复发。