Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease

Authors

Xiaoqin Wu
Xiude Fan
Tatsunori Miyata
Adam Kim
Christina K Cajigas-Du Ross
Semanti Ray
Emily Huang
Moyinoluwa Taiwo
Rakesh Arya
Jianguo Wu
Laura E Nagy

Publication Date

1-24-2023

Journal

Annual Review of Pathology: Mechanisms of Disease

Abstract

Alcohol-associated liver disease (ALD) is one of the major diseases arising from chronic alcohol consumption and is one of the most common causes of liver-related morbidity and mortality. ALD includes asymptomatic liver steatosis, fibrosis, cirrhosis, and alcohol-associated hepatitis and its complications. The progression of ALD involves complex cell-cell and organ-organ interactions. We focus on the impact of alcohol on dysregulation of homeostatic mechanisms and regulation of injury and repair in the liver. In particular, we discuss recent advances in understanding the disruption of balance between programmed cell death and prosurvival pathways, such as autophagy and membrane trafficking, in the pathogenesis of ALD. We also summarize current understanding of innate immune responses, liver sinusoidal endothelial cell dysfunction and hepatic stellate cell activation, and gut-liver and adipose-liver cross talk in response to ethanol. In addition,we describe the current potential therapeutic targets and clinical trials aimed at alleviating hepatocyte injury, reducing inflammatory responses, and targeting gut microbiota, for the treatment of ALD.

Keywords

Humans, Liver Diseases, Alcoholic, Liver, Ethanol, Hepatocytes, Fibrosis, alcohol-associated liver disease, ALD, programmed cell death, PCD, pattern recognition receptors, PRR, complement, gut-liver axis

Comments

PMID: 36270295