Warfarin anticoagulation for liver fibrosis in patients transplanted for Hepatitis C virus infection

华法林抗凝治疗丙型肝炎病毒感染移植患者的肝纤维化

• 批准号: G0701716/1
• 负责人: Mark Thursz
• 金额: $ 86.59万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0701716%2F1
• 关键词: Warfarin; anticoagulation; liver; fibrosis; patients

Hepatitis C virus (HCV) persistently infects over 200 million people worldwide, causing inflammation in the liver leading to fibrosis or scarring,and eventually cirrhosis. The current available treatment is only successful in half of patients, is expensive, and can have unpleasant side effects. Mice models of liver fibrosis have shown that mice who have a predisposed tendency to coagulate (thrombose) their blood (a prothrombotic tendency) develop liver fibrosis more rapidly than normal mice, and if given anticoagulation the rate of fibrosis is rapidly reduced. Patients who are genetically predisposed to coagulate their blood more rapidly than normal are also more likely to develop rapid liver fibrosis if infected with Hepatitis C virus. Anticoagulation is widely used to treat a variety of conditions and has also been used to treat lung fibrosis, with a 50% reduction in mortality without any anticoagulation related complications. We believe anticoagulation may provide a simple and safe intervention to slow or prevent fibrosis in patients with Hepatitis C virus . The study will be a multi-centre clinical trial of anticoagulation in patients transplanted for HCV infection. The treatment group will receive warfarin for 2 years, and liver biopsies will be performed annually, as per their routine clinical care. All patients will be screened for prothrombic tendencies. We will also evaluate non-invasive tests for liver fibrosis.If anticoagulation safely prevents or slows liver fibrosis, this could lead to it being widely used in liver transplant recipients with HCV infection. Furthermore it may lead to its use as an anti-fibrotic irrespective of the aetiology of liver fibrosis in the future.

丙型肝炎病毒（HCV）持续感染全球超过2亿人，引起肝脏炎症，导致纤维化或瘢痕形成，最终导致肝硬化。目前可用的治疗方法只对一半的患者有效，而且价格昂贵，还可能产生令人不快的副作用。肝纤维化小鼠模型表明，具有血液凝固倾向（血栓形成倾向）的小鼠比正常小鼠更快地发生肝纤维化，如果给予抗凝剂，纤维化的速度会迅速降低。在遗传上易于比正常人更快凝固血液的患者，如果感染丙型肝炎病毒，也更容易发生快速肝纤维化。抗凝被广泛用于治疗各种疾病，也被用于治疗肺纤维化，死亡率降低50%，无任何抗凝相关并发症。我们相信抗凝治疗可以提供一种简单而安全的干预措施，以减缓或预防丙型肝炎病毒患者的纤维化。该研究将是一项针对丙肝病毒感染移植患者抗凝治疗的多中心临床试验。治疗组接受华法林治疗2年，每年进行肝脏活检，按照常规临床护理。所有患者都将接受血栓形成倾向筛查。我们还将评估肝纤维化的非侵入性检查。如果抗凝可以安全地预防或减缓肝纤维化，这可能会导致它被广泛应用于HCV感染的肝移植受者。此外，它可能导致其用作抗纤维化，而不管肝纤维化的病因在未来。