Alcohol Modulation of the Postburn Hepatic Response

Abstract

The widespread and rapidly increasing trend of binge drinking is accompanied by a concomitant rise in the prevalence of trauma patients under the influence of alcohol at the time of their injury. Epidemiological evidence suggests up to half of all adult burn patients are intoxicated at the time of admission, and the presence of alcohol is an independent risk factor for death in the early stages post burn. As the major site of alcohol metabolism and toxicity, the liver is a critical determinant of postburn outcome, and experimental evidence implies an injury threshold exists beyond which burn-induced hepatic derangement is observed. Alcohol may lower this threshold for postburn hepatic damage through a variety of mechanisms including modulation of extrahepatic events, alteration of the gut-liver axis, and changes in signaling pathways. The direct and indirect effects of alcohol may prime the liver for the second-hit of many overlapping physiologic responses to burn injury. In an effort to gain a deeper understanding of how alcohol potentiates postburn hepatic damage, the authors summarize possible mechanisms by which alcohol modulates the postburn hepatic response.

Figure 1

Overlapping responses to burn injury and alcohol exposure alter the gut-liver axis. interleukin-6 (IL-6), Kupffer cells (KC), lipopolysaccharide (LPS), tumor necrosis factor (TNF)

Figure 2

Potential signaling pathway alterations in Kupffer cells after alcohol and/or burn injury. activator protein-1 (AP-1), alpha-2a adrenoceptor (α_2A-AR), cluster of differentiation 14 (CD14), inhibitor of kappa B (IκB), interleukin-1 receptor-associated kinase (IRAK), interleukin-6 (IL-6), endoplasmic reticulum (ER), lipopolysaccharide (LPS), LPS binding protein (LBP), nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase), nuclear factor kappa B (NF-κB), Toll-like Receptor 4 (TLR4), tumor necrosis factor (TNF). Numbers in figure 2 denote associated references. *Chen et al, in preparation

Figure 3

Mechanisms of steatosis development after burn injury and/or alcohol intoxication. Acetyl coenzyme A (acetyl CoA), glycerol 3-phosphate (glycerol 3-p), nicotinamide adenine dinucleotide (NAD), triglyceride (TG), very low-density lipoprotein (VLDL)