Department of Infectious Diseases, Translational Laboratory of Liver Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Laboratory of Liver Diseases, National Institute On Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20892, USA.
Hepatol Int. 2020 Sep;14(5):667-676. doi: 10.1007/s12072-020-10082-6. Epub 2020 Sep 5.
Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and progressive inflammatory liver injury in patients with a history of prolonged periods of excess alcohol consumption and recent heavy alcohol abuse. Severe AH is a life-threatening form of alcohol-associated liver disease with a high short-term mortality rate around 30-50% at one month from the initial presentation. A large number of pro-inflammatory mediators, metabolic pathways, transcriptional factors and epigenetic factors have been suggested to be associated with the development and progression of AH. Several factors may contribute to liver failure and mortality in patients with severe AH including hepatocyte death, inflammation, and impaired liver regeneration. Although the pathogeneses of AH have been extensively investigated and many therapeutic targets have been identified over the last five decades, no new drugs for AH have been successfully developed. In this review, we discuss interleukin-22 (IL-22) biology and its roles of anti-apoptosis, anti-fibrosis, anti-oxidation, anti-bacterial infection and regenerative stimulation in protecting against liver injury in many preclinical models including several recently developed models such as chronic-plus-binge ethanol feeding, acute-on-chronic liver failure, C-X-C motif chemokine ligand 1 plus high-fat diet-induced nonalcoholic steatohepatitis. Finally, clinical trials of IL-22 for the treatment of AH are also discussed, which showed some promising benefits for AH patients.
酒精性肝炎（AH）是一种临床综合征，其特征为黄疸和进行性炎症性肝损伤，患者有长期过量饮酒史和近期大量酗酒史。严重 AH 是一种危及生命的酒精相关性肝病形式，在初始表现后一个月内的短期死亡率约为 30-50%。大量促炎介质、代谢途径、转录因子和表观遗传因素被认为与 AH 的发生和发展有关。一些因素可能导致严重 AH 患者发生肝衰竭和死亡，包括肝细胞死亡、炎症和受损的肝再生。尽管 AH 的发病机制在过去五十年中得到了广泛研究，并且已经确定了许多治疗靶点，但仍然没有成功开发出用于 AH 的新药。在这篇综述中，我们讨论了白细胞介素-22（IL-22）的生物学特性及其在许多临床前模型（包括最近开发的一些模型，如慢性加 binge 乙醇喂养、慢性肝衰竭急性加重、C-X-C 基序趋化因子配体 1 加高脂肪饮食诱导的非酒精性脂肪性肝炎）中对抗肝损伤的抗凋亡、抗纤维化、抗氧化、抗细菌感染和再生刺激作用。最后，还讨论了 IL-22 治疗 AH 的临床试验，这些试验显示了对 AH 患者的一些有希望的益处。
