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Alcohol, higher BMI, rs738409 genotype increased NAFLD activity

Elevated nonalcoholic fatty liver disease activity score was linked to alcohol consumption, increased BMI and certain rs738409 genotypes, but alcohol and BMI also had a negative interaction with fibrosis in a recent study.

Researchers evaluated data from the autopsies of 405 adults who died in car accidents between 2000 and 2010 in Kansas and Missouri, including 170 alcohol-related and 235 nonalcohol-related cases. Those with blood alcohol concentrations of 0.08% or greater at autopsy were included in the alcoholic group. Genotyping for rs738409 also was performed in each case, with genotype CC observed in 233 cases, CG in 141 and GG in 31.

Within the alcohol-related cohort, age-standardized prevalence was higher for hepatic steatosis (56% vs. 36%), steatohepatitis (6% vs. 4%) and advanced fibrosis (18% vs. 6%) compared with the nonalcoholic cohort. Hepatic fibrosis at any stage was present in 42% of subjects in the alcoholic cohort and in 30% of nonalcoholic subjects.

Higher nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) was associated with the involvement of alcohol (OR=3.5; 95% CI, 2.0-5.9) and elevated BMI (OR=1.9; 95% CI, 1.7-2.5 for every 5-unit BMI increase). Investigators noted a negative association between advanced fibrosis and alcohol and BMI (P=.045), and that nonalcoholic subjects with higher BMI were at increased fibrosis risk (OR=2.2; 95% CI, 1.5-2.5 for every 5-unit increase). No association between BMI and fibrosis was observed within the alcoholic cohort (OR=0.84; 95% CI, 0.66-3.1).

Hepatic fibrosis was not associated with the CC genotype (OR=1.2; 95% CI, 0.76-2.0), nor fibrosis and the GC/GG genotype on initial analysis. Comparisons across fibrosis stages 0-2 vs. 3-4, however, showed increased risk associated with GC/GG (OR=3.2; 95% CI, 1.4-7.3). Subjects with GC or GG genotypes also were at elevated risk for a higher NAS (OR=1.9; 95% CI, 1.2-2.9).

“This study provided an assessment of fatty liver histology in the general population from an autopsy perspective, which was not possible with previous surrogate marker studies and patient case series,” the researchers wrote. “The finding of additive interaction among rs738409, obesity and alcohol toward NAS may be useful in targeting preventive care to patients at highest risk for [alcoholic liver disease]. The negative interaction between alcohol and obesity toward fibrosis justifies future research … and may lead to improved treatment to prevent fibrosis.”