Alcohol-associated Liver Disease

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2024 Feb 1

PMID 38299591

Authors

Bryan Mackowiak

Yaojie Fu

Luca Maccioni

Bin Gao

Affiliations

Soon will be listed here.

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.

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References

Schmalz F, Fischer J, Innes H, Buch S, Moller C, Matz-Soja M . High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis. JHEP Rep. 2023; 5(4):100684. PMC: 9985032. DOI: 10.1016/j.jhepr.2023.100684. View

Weichselbaum L, Azouz A, Smolen K, Das J, Splittgerber M, Lepida A . Epigenetic basis for monocyte dysfunction in patients with severe alcoholic hepatitis. J Hepatol. 2020; 73(2):303-314. DOI: 10.1016/j.jhep.2020.02.017. View

Liu X, Rosenthal S, Meshgin N, Baglieri J, Musallam S, Diggle K . Primary Alcohol-Activated Human and Mouse Hepatic Stellate Cells Share Similarities in Gene-Expression Profiles. Hepatol Commun. 2020; 4(4):606-626. PMC: 7109347. DOI: 10.1002/hep4.1483. View

Mutlu E, Keshavarzian A, Engen P, Forsyth C, Sikaroodi M, Gillevet P . Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. Alcohol Clin Exp Res. 2009; 33(10):1836-46. PMC: 3684271. DOI: 10.1111/j.1530-0277.2009.01022.x. View

Guillot A, Winkler M, Afonso M, Aggarwal A, Lopez D, Berger H . Mapping the hepatic immune landscape identifies monocytic macrophages as key drivers of steatohepatitis and cholangiopathy progression. Hepatology. 2023; 78(1):150-166. DOI: 10.1097/HEP.0000000000000270. View

Aguilar-Bravo B, Rodrigo-Torres D, Arino S, Coll M, Pose E, Blaya D . Ductular Reaction Cells Display an Inflammatory Profile and Recruit Neutrophils in Alcoholic Hepatitis. Hepatology. 2018; 69(5):2180-2195. PMC: 9189898. DOI: 10.1002/hep.30472. View

Wu X, Fan X, McMullen M, Miyata T, Kim A, Pathak V . Macrophage-derived MLKL in alcohol-associated liver disease: Regulation of phagocytosis. Hepatology. 2022; 77(3):902-919. PMC: 9741663. DOI: 10.1002/hep.32612. View

Sato K, Marzioni M, Meng F, Francis H, Glaser S, Alpini G . Ductular Reaction in Liver Diseases: Pathological Mechanisms and Translational Significances. Hepatology. 2018; 69(1):420-430. PMC: 6324973. DOI: 10.1002/hep.30150. View

Louvet A, Thursz M, Kim D, Labreuche J, Atkinson S, Sidhu S . Corticosteroids Reduce Risk of Death Within 28 Days for Patients With Severe Alcoholic Hepatitis, Compared With Pentoxifylline or Placebo-a Meta-analysis of Individual Data From Controlled Trials. Gastroenterology. 2018; 155(2):458-468.e8. DOI: 10.1053/j.gastro.2018.05.011. View

10.

Szabo G . Women and alcoholic liver disease - warning of a silent danger. Nat Rev Gastroenterol Hepatol. 2018; 15(5):253-254. DOI: 10.1038/nrgastro.2018.8. View

11.

Polimanti R, Gelernter J . ADH1B: From alcoholism, natural selection, and cancer to the human phenome. Am J Med Genet B Neuropsychiatr Genet. 2017; 177(2):113-125. PMC: 5617762. DOI: 10.1002/ajmg.b.32523. View

12.

Bloom P, Donlan J, Torres Soto M, Daidone M, Hohmann E, Chung R . Fecal microbiota transplant improves cognition in hepatic encephalopathy and its effect varies by donor and recipient. Hepatol Commun. 2022; 6(8):2079-2089. PMC: 9315114. DOI: 10.1002/hep4.1950. View

13.

Qian H, Chao X, Williams J, Fulte S, Li T, Yang L . Autophagy in liver diseases: A review. Mol Aspects Med. 2021; 82:100973. PMC: 9585624. DOI: 10.1016/j.mam.2021.100973. View

14.

Rinella M, Lazarus J, Ratziu V, Francque S, Sanyal A, Kanwal F . A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023; 79(6):1542-1556. DOI: 10.1016/j.jhep.2023.06.003. View

15.

Singal A, Shah V, Malhi H . Emerging targets for therapy in ALD: Lessons from NASH. Hepatology. 2023; 80(1):223-237. PMC: 10511666. DOI: 10.1097/HEP.0000000000000381. View

16.

Gao B, Bataller R . Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 2011; 141(5):1572-85. PMC: 3214974. DOI: 10.1053/j.gastro.2011.09.002. View

17.

Gao B, Xu M, Bertola A, Wang H, Zhou Z, Liangpunsakul S . Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance. Gene Expr. 2017; 17(3):173-186. PMC: 5500917. DOI: 10.3727/105221617X695519. View

18.

Beaudoin J, Long N, Liangpunsakul S, Puri P, Kamath P, Shah V . An exploratory genome-wide analysis of genetic risk for alcoholic hepatitis. Scand J Gastroenterol. 2017; 52(11):1263-1269. PMC: 5773288. DOI: 10.1080/00365521.2017.1359664. View

19.

Ambade A, Lowe P, Kodys K, Catalano D, Gyongyosi B, Cho Y . Pharmacological Inhibition of CCR2/5 Signaling Prevents and Reverses Alcohol-Induced Liver Damage, Steatosis, and Inflammation in Mice. Hepatology. 2018; 69(3):1105-1121. PMC: 6393202. DOI: 10.1002/hep.30249. View

20.

Homann N, Stickel F, Konig I, Jacobs A, Junghanns K, Benesova M . Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers. Int J Cancer. 2005; 118(8):1998-2002. DOI: 10.1002/ijc.21583. View