ONE OF THE ‘Top Posters’ presented at the European Association for the Study of the Liver (EASL) Congress 2025 has challenged longstanding assumptions about the role of alcohol consumption in fatty liver disease, revealing no causal link in a large Taiwanese population.
Despite a global rise in fatty liver cases, particularly in Asia, where prevalence increased from 25.3%–33.9% over less than two decades, this new study suggests that alcohol may not be the primary driver, at least in this demographic.
Using Mendelian randomisation (MR), a method that leverages genetic variants as proxies to infer causality, researchers examined data from over 120,000 Taiwanese adults aged 37–60. After excluding individuals with viral hepatitis or missing information, the analysis focused on 104,802 participants. Fatty liver was defined using the Fatty Liver Index (FLI), with a score of 20 or more indicating disease.
The study investigated whether genetic variations associated with alcohol metabolism, specifically in the ADH1A, ADH1B, ADH1C, and ALDH2 genes, could establish a causal link between drinking and fatty liver. While four significant variants were initially identified, only two (ADH1B rs1229984 and ALDH2 rs75162023) met the stringent MR criteria, showing a reliable association with alcohol consumption without being influenced by confounders such as smoking or income.
When these valid genetic instruments were used in MR analysis, the results showed no statistically significant causal effect of alcohol consumption on fatty liver. In contrast, the two variants that did not meet MR assumptions falsely suggested strong associations, underscoring the critical importance of methodological rigour in such studies.
The findings suggest that lifestyle factors beyond alcohol, such as diet and physical inactivity, may play a more substantial role in fatty liver development. As the global burden of this disease continues to grow, further research, including genome-wide association studies (GWAS), is needed to disentangle the complex interplay of genetic and behavioural factors.
Reference
Wu YC et al. Examining the causal link between alcohol consumption and fatty liver disease using Mendelian randomization. Abstract TOP-018. EASL Congress, 7-10 May, 2025.
