Alcohol-associated liver disease
Bryan Mackowiak, … , Luca Maccioni, Bin Gao
Bryan Mackowiak, … , Luca Maccioni, Bin Gao
Published February 1, 2024
Citation Information: J Clin Invest. 2024;134(3):e176345. https://doi.org/10.1172/JCI176345.
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Review

Alcohol-associated liver disease

Abstract

Alcohol-associated liver disease (ALD) is a major cause of chronic liver disease worldwide, and comprises a spectrum of several different disorders, including simple steatosis, steatohepatitis, cirrhosis, and superimposed hepatocellular carcinoma. Although tremendous progress has been made in the field of ALD over the last 20 years, the pathogenesis of ALD remains obscure, and there are currently no FDA-approved drugs for the treatment of ALD. In this Review, we discuss new insights into the pathogenesis and therapeutic targets of ALD, utilizing the study of multiomics and other cutting-edge approaches. The potential translation of these studies into clinical practice and therapy is deliberated. We also discuss preclinical models of ALD, interplay of ALD and metabolic dysfunction, alcohol-associated liver cancer, the heterogeneity of ALD, and some potential translational research prospects for ALD.

Authors

Bryan Mackowiak, Yaojie Fu, Luca Maccioni, Bin Gao

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Figure 3

Inflammation in ALD.

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Inflammation in ALD. Alcohol-associated steatohepatitis (ASH) is charact...
Alcohol-associated steatohepatitis (ASH) is characterized by hepatic infiltration of a large number of inflammatory cells, with predominant neutrophil and macrophage infiltration. Kupffer cells are activated at the early stage of ALD but are markedly reduced in the late stages of ALD, such as cirrhosis. ALD is also associated with infiltration of a significant number of T cells, but their subtypes and functions have not been well characterized. ALD, especially severe AH, is associated with infiltration of B cells and massive antibody deposition. The subsets and functions of inflammatory cells will be likely identified by single-cell and spatial transcriptomics and multiplex immunofluorescent staining analysis over the coming years. ASH is also associated with elevation of a large number of proinflammatory cytokines, chemokines, and adhesion molecules, which have overlapping functions and synergistically promote liver inflammation.