The interaction of rs738409, obesity, and alcohol: a population-based autopsy study

The objective of this study was to access the prevalence of alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) histology in the general population, which had been otherwise difficult to access because of inherent misclassification bias in surrogate marker studies and referral bias in patient case series. The interaction among rs738409, obesity, and alcohol remains controversial. This population-based autopsy study investigated the histological prevalence of ALD and NAFLD, and interactions among rs738409, obesity, and alcoholism.

A total of 170 alcoholic and 235 nonalcoholic cases were selected from 1,034 adult car accident autopsies in 17 Kansas and Missouri counties from 2000 to 2010. The nonalcoholic group had undetectable blood alcohol concentration, while the alcoholic group had a blood alcohol concentration ≥0.08%.

The age-standardized prevalences of hepatic steatosis, steatohepatitis, and advanced fibrosis were 56, 6, and 18% among alcoholics and 36, 4, and 6% in nonalcoholics, respectively. The interaction terms among alcohol, body mass index (BMI), and genotype were not significant. rs738409 GC or GG genotype was associated with 1.9-fold odds (95% confidence interval (CI), 1.2-2.9) of a higher NAFLD Activity Score (NAS). Alcohol had 3.5-fold odds (95% CI, 2.0-5.9), while every 5-unit increase in BMI had 1.9-fold odds (95% CI, 1.7-2.5). A negative interaction between alcohol and BMI towards fibrosis had been observed (P=0.045). Every 5-unit increase in BMI had 2.2-fold odds (95% CI, 1.5-2.5) of fibrosis among nonalcoholics, but not in alcoholics.

This study assessed the prevalence of fatty liver histology in the general population from an autopsy study perspective. The finding of an additive interaction among rs738409, obesity, and alcohol towards NAS may be useful in targeting preventative care to patients at highest risk for ALD. The negative interaction between alcohol and obesity towards fibrosis supported previous findings and suggests the need for future research to explore potential mechanisms that may improve treatment of nonalcoholic steatohepatitis-related fibrosis.