Wang Xiaobo
Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Med Rev (2021). 2022 Sep 13;2(4):328-330. doi: 10.1515/mr-2022-0024. eCollection 2022 Aug.
Nonalcoholic steatohepatitis (NASH) has emerged as the leading cause of chronic liver disease worldwide and is rapidly increasing in prevalence due to the obesity epidemic. There are currently no Food and Drug Administration (FDA) approved drugs to treat NASH, and therefore a critical need exists for novel therapies that can halt or reverse the progression to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Clinical trials to date using single drugs to treat NASH have shown disappointing efficacy. Combination therapies to attack different targets underlying disease pathogenesis of NASH are being explored as a strategy currently. Novel RNA therapies are also being developed to target previously "undruggable" targets and are close to the maturity necessary to be viable therapeutic approaches for the treatment of NASH and fibrosis. Identifying circulating biomarkers of fibrosis could serve as a valuable, non-invasive diagnostic tool to guide clinical practice. Despite progress in translational and clinical research, one of the major reasons for the absence of effective therapeutics is our incomplete understanding of the pathophysiology that underlies the progression from steatosis to NASH and its most deadly consequence-fibrosis. Multi-omics platforms will help to drive effective precision medicine development in NASH and hepatology.
非酒精性脂肪性肝炎（NASH）已成为全球慢性肝病的主要病因，并且由于肥胖症的流行，其患病率正在迅速上升。目前尚无美国食品药品监督管理局（FDA）批准的治疗NASH的药物，因此迫切需要能够阻止或逆转向肝纤维化、肝硬化和肝细胞癌进展的新型疗法。迄今为止，使用单一药物治疗NASH的临床试验疗效令人失望。目前正在探索联合疗法以针对NASH疾病发病机制的不同靶点，作为一种策略。新型RNA疗法也正在开发中，以针对以前“不可成药”的靶点，并且已接近成为治疗NASH和纤维化可行治疗方法所需的成熟度。识别纤维化的循环生物标志物可作为一种有价值的非侵入性诊断工具来指导临床实践。尽管在转化研究和临床研究方面取得了进展，但缺乏有效治疗方法的主要原因之一是我们对从脂肪变性发展到NASH及其最致命后果——纤维化的病理生理学理解不完整。多组学平台将有助于推动NASH和肝病学领域有效精准医学的发展。
