Modifiable lifestyle factors, genetic and acquired risk, and the risk of severe liver disease in the UK Biobank cohort

Background Lifestyle intervention is important for the treatment of liver diseases. Aims To clarify the association of healthy lifestyle with severe liver disease (SLD) and assessed whether genetic susceptibility and acquired fibrosis risk can modify the association. Methods We included 417,986 UK Biobank participants who were free of SLD at baseline. Information on seven modifiable lifestyle factors was collected through a baseline questionnaire. SLD was defined as a medical diagnosis of cirrhosis, hepatocellular carcinoma or liver failure. Cox proportional hazards models were used to evaluate the association between healthy lifestyle factors and risk of incident SLD. The polygenic risk score (PRS) and fibrosis-4 index (FIB-4) were calculated and set as an interaction term. Results During a median follow-up of 12.6 years, 4542 fatal and non-fatal SLD incidents were identified. A higher overall lifestyle score was associated with a significantly lower SLD risk (Ptrend <0.001). An increment of 1-point lifestyle score combined with a 1-SD increment in FIB-4 or PRS was associated with an additional reduction of 3% or 2% in SLD risk. Conclusions In European individuals, a healthy lifestyle is associated with a lower risk of incident SLD, which is more pronounced among individuals with a higher genetic and fibrosis risk.