Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, 3015 CE Rotterdam, The Netherlands.
Nat Rev Gastroenterol Hepatol. 2012 Apr 17;9(6):355-62. doi: 10.1038/nrgastro.2012.67.
Liver transplantation is an effective treatment for end-stage liver disease that is attributable to chronic HCV infection. However, long-term outcomes are compromised by universal virological recurrence in the graft. Reinfection that occurs after transplantation has increased resistance to current interferon-based antiviral therapy and often leads to accelerated development of cirrhosis. Important risk factors for severe HCV recurrence are linked to immunosuppression. Owing to the lack of good randomized, controlled trials, the optimal choice of immunosuppressants is still debated. By contrast, much progress has been made in the understanding of HCV biology and the antiviral action of interferons. These new insights have greatly expanded our knowledge of the molecular interplay between HCV and immunosuppressive drugs. In this article, we explore the effect of different immunosuppressants on the complex cellular events involved in HCV infection and interferon signalling. Potential implications for clinical practice and future drug development are discussed.
肝移植是一种有效的治疗方法,适用于由慢性 HCV 感染引起的终末期肝病。然而,由于移植物中普遍存在病毒学复发,长期预后受到影响。移植后发生的再感染对目前基于干扰素的抗病毒治疗具有耐药性,并且常常导致肝硬化加速发展。严重 HCV 复发的重要危险因素与免疫抑制有关。由于缺乏良好的随机对照试验,免疫抑制剂的最佳选择仍存在争议。相比之下,人们对 HCV 生物学和干扰素抗病毒作用的认识已经取得了很大的进展。这些新的见解极大地扩展了我们对 HCV 与免疫抑制药物之间分子相互作用的认识。在本文中,我们探讨了不同免疫抑制剂对 HCV 感染和干扰素信号转导涉及的复杂细胞事件的影响。讨论了其对临床实践和未来药物开发的潜在影响。