Huisman Tsipora M, Dieterich Douglas T, Friedman Scott L
Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
J Exp Pharmacol. 2021 Mar 18;13:329-338. doi: 10.2147/JEP.S265286. eCollection 2021.
There have been major advances in the treatment of HBV and HCV with anti-viral treatments, which is reducing the prevalence of fibrosis due to these viruses and obviating the need for anti-fibrotic therapies in these diseases. At the same time, however, the prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing, of which a substantial fraction of patients have non-alcoholic steatohepatitis (NASH), which may progress to cirrhosis. Accordingly, NASH is emerging as the leading indication for liver transplantation in North America and Europe. Progress in uncovering pathogenic determinants of fibrosis in NASH include metabolic dysregulation in hepatocytes that induce inflammation and cytokine secretion leading to cell injury and apoptosis, among others. These pathogenic events converge upon hepatic stellate cells, which are the primary fibrogenic cell in liver, and represent a target of new therapeutic candidates that are currently being evaluated in animal models and clinical trials. This review highlights key experimental and investigational therapies for NASH fibrosis, whose evaluation will be accelerated as new non-invasive markers of fibrosis are established. While no drugs are approved yet for NASH fibrosis, there is growing optimism that new pharmacotherapies are likely to emerge within the next 3 years that will favorably alter the natural history of disease.
抗病毒治疗在乙肝病毒（HBV）和丙肝病毒（HCV）的治疗方面取得了重大进展，这降低了由这些病毒导致的肝纤维化患病率，并且不再需要针对这些疾病进行抗纤维化治疗。然而，与此同时，非酒精性脂肪性肝病（NAFLD）的患病率一直在上升，其中相当一部分患者患有非酒精性脂肪性肝炎（NASH），后者可能会发展为肝硬化。因此，NASH正成为北美和欧洲肝移植的主要指征。在揭示NASH肝纤维化的致病决定因素方面取得的进展包括肝细胞中的代谢失调，这种失调会引发炎症和细胞因子分泌，进而导致细胞损伤和凋亡等。这些致病事件都集中在肝星状细胞上，肝星状细胞是肝脏中主要的纤维化细胞，是目前正在动物模型和临床试验中评估的新治疗候选药物的靶点。本综述重点介绍了针对NASH肝纤维化的关键实验性和研究性疗法，随着新的肝纤维化非侵入性标志物的建立，对这些疗法的评估将加速。虽然目前尚无药物获批用于治疗NASH肝纤维化，但人们越来越乐观地认为，未来3年内可能会出现新的药物疗法，从而有利地改变疾病的自然病程。
