Alcoholic, Nonalcoholic, and Toxicant-Associated Steatohepatitis: Mechanistic Similarities and Differences

Cell Mol Gastroenterol Hepatol. 2015 Jun 3;1(4):356-367. doi: 10.1016/j.jcmgh.2015.05.006. eCollection 2015 Jul.


Hepatic steatosis and steatohepatitis are common histologic findings that can be caused by multiple etiologies. The three most frequent causes for steatosis/steatohepatitis are alcohol (alcoholic steatohepatitis, ASH), obesity/metabolic syndrome (nonalcoholic steatohepatitis, NASH), and environmental toxicants (toxicant-associated steatohepatitis, TASH). Hepatic steatosis is an early occurrence in all three forms of liver disease, and they often share common pathways to disease progression/severity. Disease progression is a result of both direct effects on the liver as well as indirect alterations in other organs/tissues such as intestine, adipose tissue, and the immune system. Although the three liver diseases (ASH, NASH, and TASH) share many common pathogenic mechanisms, they also exhibit distinct differences. Both shared and divergent mechanisms can be potential therapeutic targets. This review provides an overview of selected important mechanistic similarities and differences in ASH, NASH, and TASH.

Keywords: ALD, alcoholic liver disease; ALT, alanine aminotransferase; ASH, alcoholic steatohepatitis; AST, aspartate transaminase; Alcoholic Steatohepatitis; BMI, body mass index; CYP2E1, cytochrome P450 isoform 2E1; ECM, extracellular matrix; ER, endoplasmic reticulum; HCC, hepatocellular carcinoma; HDAC, histone deacetylase; HSC, hepatic stellate cell; IL, interleukin; LA, linoleic acid; LPS, lipopolysaccharide; Mechanisms; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NK, natural killer; NKT, natural killer T; Nonalcoholic Steatohepatitis; OXLAM, oxidized linoleic acid metabolite; PAI-1, plasminogen activator inhibitor-1; PCB153, 2,2′,4,4′,5,5′-hexachlorobiphenyl; PPAR, peroxisome proliferator-activated receptor; RNS, reactive nitrogen species; SNP, single-nucleotide polymorphism; TAFLD, toxicant-associated fatty liver disease; TASH, toxicant-associated steatohepatitis; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TH, helper T cell; TLR, Toll-like receptor; TNF, tumor necrosis factor; Toxicant-Associated Steatohepatitis; VA, U.S. Department of Veterans Affairs/Veterans Administration; miR, microRNA.

Publication types

  • Review