Shift work and evening chronotype are related to prevalent non-alcoholic fatty liver disease in 282,303 UK biobank participants

Abstract Background & Aims Non-alcoholic fatty liver disease (NAFLD) is globally prevalent and confers a high risk of morbidity via progression to non-alcoholic steatohepatitis (NASH). Circadian disruption in mouse models contributes to the development of hepatic steatosis and inflammation, however evidence in humans is lacking. We investigated how shift working and chronotype were associated with NAFLD/NASH in UK Biobank participants. Methods We stratified 282,303 UK Biobank participants into day, irregular-shift, and permanent night-shift workers. We compared the likelihood of NAFLD/NASH in these groups using: a) Dallas Steatosis Index (DSI), b) NAFLD/NASH ICD10 codes, and c) liver proton density fat fraction (PDFF) after serially adjusting for age, sex, ethnicity, sleep, alcohol, smoking, and body mass index. We further assessed the relationship of baseline chronotype with likelihood of NAFLD/NASH using the same outcomes and covariates. Results Compared to day workers, irregular-shift workers were more likely to have NAFLD/NASH defined by high DSI (odds ratio (OR) 1.29 (95% CI 1.18–1.4)) after adjusting for all covariates excluding BMI, with some attenuation after additional adjustment for BMI (OR 1.12 (1.03-1.22)). Likelihood of DSI-defined NAFLD/NASH was also higher in permanent night-shift workers (OR 1.08 (0.9–1.29)) in the fully-adjusted model. Compared to participants with intermediate chronotype, those with extreme late chronotype had a higher likelihood of DSI-defined NAFLD/NASH (OR 1.45 (1.34–1.56)) and a higher likelihood of NAFLD/NASH by ICD10 code (OR 1.23 (1.09–1.39)). Liver PDFF was elevated in irregular shift workers, but not permanent night shift workers. Conclusions Irregular-shift work and chronotype are associated with NAFLD/NASH, suggesting circadian misalignment as an underlying mechanism. These findings have implications for health interventions to mitigate the detrimental effect of shift work.