Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, 200092, China.
Acta Pharmacol Sin. 2022 May;43(5):1191-1199. doi: 10.1038/s41401-021-00822-1. Epub 2021 Dec 14.
Currently, nonalcoholic steatohepatitis (NASH) is one of the most common forms of chronic hepatitis, increasing the burden of health care worldwide. In patients with NASH, the fibrosis stage is the most predictive factor of long-term events. However, there are still no drugs approved by the Food and Drug Administration of the United States for treating biopsy-proven NASH with fibrosis or cirrhosis. Although some novel drugs have shown promise in preclinical studies and led to improvement in terms of hepatic fat content and steatohepatitis, a considerable proportion of them have failed to achieve histological endpoints of fibrosis improvement. Due to the large number of NASH patients and adverse clinical outcomes, the search for novel drugs is necessary. In this review, we discuss current definitions for the evaluation of treatment efficacy in fibrosis improvement for NASH patients, and we summarize novel agents in the pipeline from different mechanisms and phases of trial. We also critically review the challenges we face in the development of novel agents for fibrotic NASH and NASH cirrhosis.
目前，非酒精性脂肪性肝炎（NASH）是最常见的慢性肝炎类型之一，在全球范围内增加了医疗保健负担。在 NASH 患者中，纤维化阶段是预测长期事件的最主要因素。然而，目前仍没有美国食品和药物管理局批准的药物可用于治疗经活检证实的伴有纤维化或肝硬化的 NASH。虽然一些新型药物在临床前研究中显示出前景，并在改善肝脂肪含量和脂肪性肝炎方面取得了一定的效果，但相当一部分药物未能达到纤维化改善的组织学终点。由于 NASH 患者数量众多，且临床结局不良，因此有必要寻找新型药物。在这篇综述中，我们讨论了当前用于评估 NASH 患者纤维化改善治疗效果的定义，并总结了不同机制和试验阶段的新型药物。我们还批判性地审查了在开发纤维化 NASH 和 NASH 肝硬化新型药物方面所面临的挑战。
