Associations of serum uric acid levels with liver disease‐related morbidity and mortality: A prospective cohort study of the UK Biobank

Abstract Background and Aims The association of serum uric acid (SUA) levels with liver‐related morbidity and mortality remains undetermined. Therefore, we aimed to explore the association of SUA levels with liver‐related morbidity and mortality. Methods The present cohort study included 459 619 adults from the UK Biobank. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of SUA levels with morbidity and mortality of overall liver disease. Mendelian randomization (MR) analyses were conducted to explore the underlying causality. A polygenic risk score was generated to assess whether there was a gene‐exposure interaction. Results During a median follow‐up of 12.6 years, 14 302 nonfatal and 609 fatal cases of overall liver disease were identified. Compared to individuals in the lowest quartile, the HRs (95% CI) of incident overall liver disease were 1.08 (1.02–1.14), 1.13 (1.07–1.20) and 1.44 (1.36–1.53) for individuals with SUA levels in quartiles 2, 3 and 4 respectively. Similarly, the HRs (95% CI) of liver disease‐associated mortality were 1.09 (0.78–1.52), 1.55 (1.14–2.13) and 1.96 (1.42–2.69) for individuals with SUA levels in quartiles 2, 3 and 4 respectively. The MR results did not support the causal association of SUA levels with liver disease. In addition, there was a significant modification effect of the polygenic risk score on the association of SUA levels with incident overall liver disease ( p interaction = .003). Conclusions Higher SUA levels were significantly associated with an increased risk of overall liver disease morbidity and mortality.