Liu Zhening, Huang Hangkai, Xie Jiarong, Xu Chengfu
Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Department of Gastroenterology, Ningbo First Hospital, Ningbo, 315010, China.
Liver Int. 2023 May;43(5):1046-1055. doi: 10.1111/liv.15564. Epub 2023 Mar 29.
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.
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.
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 = .003).
Higher SUA levels were significantly associated with an increased risk of overall liver disease morbidity and mortality.
血清尿酸（SUA）水平与肝脏相关发病率和死亡率之间的关联尚未明确。因此，我们旨在探讨SUA水平与肝脏相关发病率和死亡率之间的关联。
本队列研究纳入了英国生物银行的459619名成年人。采用多变量Cox比例风险模型估计SUA水平与总体肝病发病率和死亡率之间关联的风险比（HR）和95%置信区间（CI）。进行孟德尔随机化（MR）分析以探究潜在因果关系。生成多基因风险评分以评估是否存在基因-暴露相互作用。
在中位随访12.6年期间，共识别出14302例总体肝病非致命病例和609例致命病例。与最低四分位数组的个体相比，SUA水平处于第二、第三和第四四分位数组的个体发生总体肝病的HR（95%CI）分别为1.08（1.02 - 1.14）、1.13（1.07 - 1.20）和1.44（1.36 - 1.53）。同样，SUA水平处于第二、第三和第四四分位数组的个体肝病相关死亡率的HR（95%CI）分别为1.09（0.78 - 1.52）、1.55（1.14 - 2.13）和1.96（1.42 - 2.69）。MR结果不支持SUA水平与肝病之间的因果关联。此外，多基因风险评分对SUA水平与总体肝病发病之间的关联有显著的修饰作用（p = 0.003）。
较高的SUA水平与总体肝病发病率和死亡率风险增加显著相关。
