Circulating total bilirubin and risk of non-alcoholic fatty liver disease in the PREVEND study: observational findings and a Mendelian randomization study

AbstractThe relationship between circulating total bilirubin and incident non-alcoholic fatty liver disease (NAFLD) is uncertain. We aimed to assess the association of total bilirubin with the risk of new-onset NAFLD and investigate any causal relevance to the association using a Mendelian randomization (MR) study. Plasma total bilirubin levels were measured at baseline in the PREVEND prospective study of 3824 participants (aged 28 –75 years) without pre-existing cardiovascular disease or NAFLD. Incident NAFLD was estimated using the biomarker-based algorithms, fatty liver index (FLI) and hepatic steatosis index (HSI). Odds ratios (ORs) (95% confidence intervals) for NAFLD were assessed. The genetic variant rs6742078 locate d in the UDP-glucuronosyltransferase (UGT1A1) locus was used as an instrumental variable. Participants were followed up for a mean duration of 4.2 years. The multivariable adjusted OR (95% CIs) for NAFLD as estimated by FLI (434 cases) was 0.82 (0.73–0.92;p  =  0.001) per 1 standard deviation (SD) change in loge total bilirubin. The corresponding adjusted OR (95% CIs) for NAFLD as estimated by HSI (452 cases) was 0.87 (0.78 –0.97;p  =  0.012). The rs6742078 variant explained 20% of bilirubin variation. The ORs (95% CIs) for a 1 SD genetically elevated total bilirubin level was 0.98 (0.69–1.38;p  =  0.900) for FLI and 1.14 (0.81–1.59;p  =  0.451) for HSI. Elevated levels of total bilirubin were not causally associated with decre...
Source: European Journal of Epidemiology - Category: Epidemiology Source Type: research