Excessive alcohol consumption is a global healthcare problem with enormous social, economic, and clinical consequences. While chronic, heavy alcohol consumption causes structural damage and/or disrupts normal organ function in virtually every tissue of the body, the liver sustains the greatest damage. This is primarily because the liver is the first to see alcohol absorbed from the gastrointestinal tract via the portal circulation and second, because the liver is the principal site of ethanol metabolism. Alcohol-induced damage remains one of the most prevalent disorders of the liver and a leading cause of death or transplantation from liver disease. Despite extensive research on the pathophysiology of this disease, there are still no targeted therapies available. Given the multifactorial mechanisms for alcohol-associated liver disease pathogenesis, it is conceivable that a multitherapeutic regimen is needed to treat different stages in the spectrum of this disease.
Keywords: AA, Arachidonic acid; ADH, Alcohol dehydrogenase; AH, Alcoholic hepatitis; ALD, Alcohol-associated liver disease; ALDH, Aldehyde dehydrogenase; ALT, Alanine transaminase; ASH, Alcohol-associated steatohepatitis; AST, Aspartate transaminase; AUD, Alcohol use disorder; BHMT, Betaine-homocysteine-methyltransferase; CD, Cluster of differentiation; COX, Cycloxygenase; CTLs, Cytotoxic T-lymphocytes; CYP, Cytochrome P450; CYP2E1, Cytochrome P450 2E1; Cu/Zn SOD, Copper/zinc superoxide dismutase; DAMPs, Damage-associated molecular patterns; DC, Dendritic cells; EDN1, Endothelin 1; ER, Endoplasmic reticulum; ETOH, Ethanol; EVs, Extracellular vesicles; FABP4, Fatty acid-binding protein 4; FAF2, Fas-associated factor family member 2; FMT, Fecal microbiota transplant; Fn14, Fibroblast growth factor-inducible 14; GHS-R1a, Growth hormone secretagogue receptor type 1a; GI, GOsteopontinastrointestinal tract; GSH Px, Glutathione peroxidase; GSSG Rdx, Glutathione reductase; GST, Glutathione-S-transferase; GWAS, Genome-wide association studies; H2O2, Hydrogen peroxide; HA, Hyaluronan; HCC, Hepatocellular carcinoma; HNE, 4-hydroxynonenal; HPMA, 3-hydroxypropylmercapturic acid; HSC, Hepatic stellate cells; HSD17B13, 17 beta hydroxy steroid dehydrogenase 13; HSP 90, Heat shock protein 90; IFN, Interferon; IL, Interleukin; IRF3, Interferon regulatory factor 3; JAK, Janus kinase; KC, Kupffer cells; LCN2, Lipocalin 2; M-D, Mallory–Denk; MAA, Malondialdehyde-acetaldehyde protein adducts; MAT, Methionine adenosyltransferase; MCP, Macrophage chemotactic protein; MDA, Malondialdehyde; MIF, Macrophage migration inhibitory factor; Mn SOD, Manganese superoxide dismutase; Mt, Mitochondrial; NK, Natural killer; NKT, Natural killer T-lymphocytes; OPN, Osteopontin; PAMP, Pathogen-associated molecular patterns; PNPLA3, Patatin-like phospholipase domain containing 3; PUFA, Polyunsaturated fatty acid; RIG1, Retinoic acid inducible gene 1; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; SCD, Stearoyl-CoA desaturase; STAT, Signal transduction and activator of transcription; TIMP1, Tissue inhibitor matrix metalloproteinase 1; TLR, Toll-like receptor; TNF, Tumor necrosis factor-α; alcohol; alcohol-associated liver disease; ethanol metabolism; liver; miRNA, MicroRNA; p90RSK, 90 kDa ribosomal S6 kinase.