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

SILVIA SOOKOIAN; CARLOS J PIROLA; DIEGO FLICHMAN; GUSTAVO O CASTAÑO

ALIMENTARY PHARMACOLOGY & THERAPEUTICS.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016 vol. 44 p. 1224 - 1234

0269-2813

BackgroundPrevious epidemiological studies suggest that patients diagnosed with nonalcoholicfatty liver disease (NAFLD) who drink light to moderate amountsof alcohol (up to ~30 g per day) have less severe histological lesions comparedwith nondrinkers. However, while the cross-sectional nature ofcurrent evidence precludes assessment of causality, cumulative lifetimeexposureof moderate alcohol consumption on histological outcomes hasnever been evaluated.AimTo overcome these limitations, a Mendelian randomisation study was performedusing a validated genetic variant (rs1229984 A;G) in the alcoholdehydrogenase (ADH1B) gene as a proxy of long-term alcohol exposure.MethodsWe first assessed whether the instrumental variant (rs1229984) was associatedwith the amount of alcohol consumption in our cohort. We furtherexplored the association between the variant and histological outcomes; asample of 466 individuals, including 266 patients with NAFLD confirmedby liver biopsy, was studied.ResultsWe found that carriers of the A-allele consumed significantly lower amountsof 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 severityshowed 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.ConclusionMendelian randomisation analysis suggests no beneficial effect of moderatealcohol consumption on NAFLD disease severity.