Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression

Natalia A Osna; Irina Tikhanovich; Martí Ortega-Ribera; Sebastian Mueller; Chaowen Zheng; Johannes Mueller; Siyuan Li; Sadatsugu Sakane; Raquel Carvalho Gontijo Weber; Hyun Young Kim; Wonseok Lee; Souradipta Ganguly; Yusuke Kimura; Xiao Liu; Debanjan Dhar; Karin Diggle; David A Brenner; Tatiana Kisseleva; Neha Attal; Iain H McKillop; Shilpa Chokshi; Ram Mahato; Karuna Rasineni; Gyongyi Szabo; Kusum K Kharbanda

doi:10.3390/biom14040404

Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression

Biomolecules. 2024 Mar 27;14(4):404. doi: 10.3390/biom14040404.

Authors

Natalia A Osna^{1

2}, Irina Tikhanovich³, Martí Ortega-Ribera⁴, Sebastian Mueller^{5

6}, Chaowen Zheng⁵, Johannes Mueller⁵, Siyuan Li⁵, Sadatsugu Sakane^{7

8}, Raquel Carvalho Gontijo Weber^{7

8}, Hyun Young Kim^{7

8}, Wonseok Lee^{7

8}, Souradipta Ganguly^{7

8}, Yusuke Kimura^{7

8}, Xiao Liu^{7

8}, Debanjan Dhar⁷, Karin Diggle^{7

8}, David A Brenner^{7

9}, Tatiana Kisseleva⁸, Neha Attal¹⁰, Iain H McKillop¹⁰, Shilpa Chokshi^{11

12}, Ram Mahato¹³, Karuna Rasineni¹⁴, Gyongyi Szabo⁴, Kusum K Kharbanda^{2

14

15}

Affiliations

¹ Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68106, USA.
² Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68106, USA.
³ Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
⁴ Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
⁵ Center for Alcohol Research, University of Heidelberg, 69120 Heidelberg, Germany.
⁶ Viscera AG Bauchmedizin, 83011 Bern, Switzerland.
⁷ Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
⁸ Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA.
⁹ Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
¹⁰ Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA.
¹¹ The Roger Williams Institute of Hepatology, Foundation for Liver Research, London SE59NT, UK.
¹² School of Microbial Sciences, King's College, London SE59NT, UK.
¹³ Department of Pharmaceutical Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68106, USA.
¹⁴ Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68106, USA.
¹⁵ Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.

Abstract

Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here, we overview several crucial mechanisms related to ALD end-stage outcome development, such as epigenetic changes, cell death, hemolysis, hepatic stellate cells activation, and hepatic fatty acid binding protein 4. Additionally, in this review, we also present two clinically relevant models using human precision-cut liver slices and hepatic organoids to examine ALD pathogenesis and progression.

Keywords: MetAld; alcohol-associated liver disease; cell death; epigenetics; fatty acid binding protein 4; fibrosis; hemolysis; hepatic stellate cells; hepatocellular carcinoma; models.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Progression*
Epigenesis, Genetic
Hepatic Stellate Cells / metabolism
Hepatic Stellate Cells / pathology
Humans
Liver / metabolism
Liver / pathology
Liver Diseases, Alcoholic* / metabolism
Liver Diseases, Alcoholic* / pathology

Grants and funding

This work was supported by the National Institute of Health grants R01 DK135817 (N.A.O. and R.M.), P50 AA030407-1529 (N.A.O.), R01 AA027586 (I.T.), R01 AA017729 (G.S.), R01 AA020744 (G.S.), R01 AA011576 (G.S.), R01 DK099205 (T.K.), R01 AA028550 (T.K.), R01 DK101737 (T.K.), R01 AA011999 (T.K.), R01 DK120515 (T.K.), R01 AA029019 (T.K.), R01 DK091183 (T.K.), R01 DK137061 (D.D.), R01 DK133930 (D.D.), R01 AA027586 (I.T.), R01 AA028524 (K.R.), RP42ES010337 (T.K.), R44DK115242 (D.A.B.), R01 AA026723 (K.K.K.), P50 AA030407-1531 (K.K.K), RA 2677/1-2 Deutsche Forschungsgemeinschaft (S.M.), The Foundation for Liver Research (S.C.), and Merit Review grants I01BX004053 (K.K.K.) and I01BX006064 (K.K.K.) from the US Department of Veterans Affairs, Biomedical Laboratory Research, and Development Service.