期刊
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
卷 41, 期 4, 页码 747-757出版社
WILEY
DOI: 10.1111/acer.13346
关键词
Alcohol-Dependent Subjects; Mild Alcoholic Liver Disease; Endotoxemia
资金
- NIH [R21 AA020849, R01 AA024102, Z99-AA999999, U01AA022489, 1U01AA021901-01, 1U01AA021893-01, R01AA023681]
- Department of Veterans Affairs [BX000350]
- Department of Defense [W81XWH-11-1-0595]
- Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM113226]
- National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health [P50AA024337]
Background: Interactions between the liver, the gut, and the immune system are critical components of alcoholic liver disease (ALD). The aim of this study was to explore the associations between alcohol-induced liver injury, endotoxemia, and inflammation at admission and over time during abstinence, as well as to examine the sex-related differences in these parameters in alcohol-dependent individuals admitted to an alcohol treatment program. Methods: A cohort of 48 otherwise healthy participants with alcohol use disorder, but no clinical signs of alcoholic liver injury (34 males [M]/14 females [F]) admitted to an alcohol detoxification program, was stratified into 2 groups based on baseline plasma alanine aminotransferase (ALT) levels (as a marker of liver injury). Group 1 (ALT<40U/l, 7M/8F) and Group 2 (ALT40U/l, 27M/6F) were identified. Plasma biomarkers of liver damage, endotoxemia, and inflammation were examined at baseline, day 8, and day 15 of the admission. The drinking history was also evaluated. Results: Sixty-nine percent of patients had elevated ALT and other markers of liver damage, including aspartate aminotransferase and cytokeratin 18 (CK18M65 and CK M30) at baseline, indicating the presence of mild ALD. Elevated CK18M65:M30 ratio suggested a greater contribution of necrotic rather than apoptotic hepatocyte cell death in the liver injury observed in these individuals. Females showed greater elevations of liver injury markers compared to males, although they had fewer drinks per day and shorter lifetime duration of heavy drinking. Liver injury was associated with systemic inflammation, specifically, elevated plasma tumor necrosis factor-alpha levels. Compared to patients without liver injury, patients with mild ALD had greater endotoxemia (increased serum lipopolysaccharide levels), which decreased with abstinence and this decrease preceded the drop in CK18M65 levels. Conclusions: The study documented the association of mild alcohol-induced liver injury and endotoxemia, which improved with 2weeks of abstinence, in a subset of individuals admitted to an alcohol detoxification program.
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