The Medical University of South Carolina, Charleston, South Carolina.
Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York.
Gastroenterology. 2021 Apr;160(5):1502-1520.e1. doi: 10.1053/j.gastro.2020.09.065. Epub 2021 Jan 30.
Hepatitis C virus (HCV) infection and its complications have been the major cause of cirrhosis and its complications for several decades in the Western world. Until recently, treatment for HCV with interferon-based regimens was associated with moderate success but was difficult to tolerate. More recently, however, an arsenal of novel and highly effective direct-acting antiviral (DAA) drugs has transformed the landscape by curing HCV in a broad range of patients, including those with established advanced fibrosis, cirrhosis, comorbidities, and even those with complications of cirrhosis. Fibrosis is a dynamic process comprising both extracellular matrix deposition, as well as its degradation. With almost universal sustained virologic response (SVR) (ie, elimination of HCV), it is timely to explore whether HCV eradication can reverse fibrosis and cirrhosis. Indeed, fibrosis in several types of liver disease is reversible, including HCV. However, we do not know with certainty in whom fibrosis regression can be expected after HCV elimination, how quickly it occurs, and whether antifibrotic therapies will be indicated in those with persistent cirrhosis. This review summarizes the evidence for reversibility of fibrosis and cirrhosis after HCV eradication, its impact on clinical outcomes, and therapeutic prospects for directly promoting fibrosis regression in patients whose fibrosis persists after SVR.
丙型肝炎病毒(HCV)感染及其并发症几十年来一直是西方世界肝硬化及其并发症的主要原因。直到最近,基于干扰素的治疗方案治疗 HCV 虽然取得了一定的成功,但患者很难耐受。然而,最近一系列新型、高效的直接作用抗病毒(DAA)药物的出现改变了这一局面,使 HCV 在广泛的患者中得到治愈,包括那些已患有晚期纤维化、肝硬化、合并症,甚至是肝硬化并发症的患者。纤维化是一个动态过程,包括细胞外基质的沉积和降解。由于几乎普遍的持续病毒学应答(SVR)(即 HCV 的消除),现在正是探讨 HCV 根除是否可以逆转纤维化和肝硬化的时机。事实上,包括 HCV 在内的几种类型的肝病的纤维化是可以逆转的。然而,我们尚不能确定在 HCV 消除后,纤维化在哪些患者中可以得到逆转,它发生的速度有多快,以及在那些持续性肝硬化患者中是否需要抗纤维化治疗。这篇综述总结了 HCV 根除后纤维化和肝硬化逆转的证据,及其对临床结局的影响,以及在 SVR 后纤维化仍然存在的患者中直接促进纤维化逆转的治疗前景。