Albanis E, Friedman S L
Division of Liver Diseases, Mount Sinai Medical Center, New York, New York, USA.
Am J Transplant. 2006 Jan;6(1):12-9. doi: 10.1111/j.1600-6143.2005.01143.x.
Complications from chronic hepatitis C (HCV) and recurrent HCV post-transplant are responsible for significant morbidity and mortality in the United States and Europe. Current antiviral therapies are at best, effective in up to 50% of patients in the pre-transplant setting, and in the post-transplant setting are associated with more limited efficacy and increased toxicity. With this reduced efficacy of antiviral strategies in the post-transplant setting, new approaches are urgently needed. Substantial progress has been made in understanding the pathogenesis of hepatic fibrosis over the last 20 years, which has yielded potential new therapeutic targets. The prospect of antifibrotic therapies is nearing reality in order to reduce progression to cirrhosis, thereby reducing morbidity, mortality and the need for re-transplantation. Current and evolving approaches primarily target the activated hepatic stellate cells, which are the main source of extracellular matrix, along with related fibrogenic cell types. Key issues yet to be clarified include the optimal duration of antifibrotic therapies, endpoints of clinical trials, indications in clinical practice and whether combination therapies might yield synergistic activity.
在美国和欧洲，慢性丙型肝炎（HCV）及移植后复发性HCV引发的并发症导致了显著的发病率和死亡率。目前的抗病毒疗法在移植前的患者中，最多只有50%有效，而在移植后的情况下，疗效更有限且毒性增加。鉴于移植后抗病毒策略的疗效降低，迫切需要新的方法。在过去20年里，人们对肝纤维化发病机制的理解取得了重大进展，这产生了潜在的新治疗靶点。抗纤维化疗法有望成为现实，以减少肝硬化的进展，从而降低发病率、死亡率和再次移植的需求。当前和不断发展的方法主要针对活化的肝星状细胞，它们是细胞外基质的主要来源，以及相关的纤维化细胞类型。尚未阐明的关键问题包括抗纤维化疗法的最佳持续时间、临床试验的终点、临床实践中的适应症以及联合疗法是否可能产生协同作用。
