Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease

BACKGROUND: Previous epidemiological studies suggest that patients diagnosed with nonalcoholic fatty liver disease (NAFLD) who drink light to moderate amounts of alcohol (up to ~30 g per day) have less severe histological lesions compared with nondrinkers. However, while the cross-sectional nature of current evidence precludes assessment of causality, cumulative lifetime-exposure of moderate alcohol consumption on histological outcomes has never been evaluated.

AIM: To overcome these limitations, a Mendelian randomisation study was performed using a validated genetic variant (rs1229984 A;G) in the alcohol dehydrogenase (ADH1B) gene as a proxy of long-term alcohol exposure.

METHODS: We first assessed whether the instrumental variant (rs1229984) was associated with the amount of alcohol consumption in our cohort. We further explored the association between the variant and histological outcomes; a sample of 466 individuals, including 266 patients with NAFLD confirmed by liver biopsy, was studied.

RESULTS: We found that carriers of the A-allele consumed significantly lower amounts of alcohol compared with noncarriers (2.3 +/- 5.3 vs. 8.18 +/- 21 g per day, mean +/- s.d., P = 0.03). The analysis of association with the disease severity showed that carriers of the A-allele had lower degree of histological steatosis (1.76 +/- 0.83 vs. 2.19 +/- 0.78, P = 0.03) and lower scores of lobular inflammation (0.54 +/- 0.65 vs. 0.95 +/- 0.92, P = 0.02) and NAFLD-Activity Score (2.9 +/- 1.4 vs. 3.7 +/- 1.4, P = 0.015) compared with noncarriers.

CONCLUSION: Mendelian randomisation analysis suggests no beneficial effect of moderate alcohol consumption on NAFLD disease severity.