title: The role of hypoxia in the pathogenesis of alcoholic liver disease.
abstract: Research on alcohol-induced liver hypoxia in experimental and clinical alcoholic liver disease (ALD) over a span of 20 years is reviewed. The data has repeatedly supported a role for hypoxia in the pathogenesis of ALD but little attention has been given to this phenomenon in a clinical setting where intervention strategies could be developed. Liver hypoxia, particularly when blood alcohol levels are high, has been documented in vivo in rats fed ethanol continuously at a constant rate for prolonged periods. In this model of ALD, the liver pathology, the liver metabolism and the gene expression differ when the livers are compared at the peak and trough blood alcohol levels as monitored daily by measuring the urinary alcohol level cycle (UAL). Genes regulated by the hypoxia-inducible factor (HIF) are expressed more at the peaks, and the livers contain more inflammation at the peaks. However, alanine aminotransferase levels are higher at the troughs suggesting that hypoxia occurs at the peaks and reperfusion injury occurs at the troughs. These findings may be relevant to binge drinking-induced liver injury where hypoxia at high BAL is followed by normoxia and reoxygination injury when BAL falls toward zero.
authors.affiliation: Department of Pathology, Harbor-UCLA Medical Center, 1000 W. Carson Street, Torrance, CA, 90509 USA.
authors.forename: Samuel W.
authors.initials: SW
authors.lastname: French