Interleukin-22 in alcoholic hepatitis and beyond
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REVIEW ARTICLE
Interleukin‑22 in alcoholic hepatitis and beyond Xiaogang Xiang1,2 · Seonghwan Hwang2 · Dechun Feng2 · Vijay H. Shah3 · Bin Gao2 Received: 11 May 2020 / Accepted: 17 August 2020 © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020
Abstract 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. Keywords Alcoholic liver disease · Liver regeneration · Inflammation · Acute-on-chronic liver failure · Nonalcoholic steatohepatitis
Introduction Alcohol-associated liver disease (ALD) is a crucial cause of liver damage, liver cirrhosis, hepatocellular carcinoma and end-stage liver diseases worldwide [1–4]. There are several major stages of ALD including alcoholic fatty liver, alcoholic steatohepatitis (ASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma [1, 5]. Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and progressive inflammatory liver injury in patients with a history
* Bin Gao [email protected] 1
Department of Infectious Diseases, Translational Laboratory of Liver Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
2
Laboratory of Liver Diseases, National Institute On Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
3
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, USA
of prolonged periods of excess alcohol consumption and recent heavy alcohol abuse [5–8]. Both chronic ALD with active alcohol binge and systemic infla
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