School of Public Health, Capital Medical University, Beijing, China; Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
Department of Information, Beijing Physical Examination Center, Beijing, China.
Atherosclerosis. 2020 Oct;311:44-51. doi: 10.1016/j.atherosclerosis.2020.08.006. Epub 2020 Aug 27.
The temporal relationship between hyperuricemia and non-alcoholic fatty liver disease (NAFLD) is debatable. This study aimed to explore whether there exists a bidirectional or temporal relationship between them.
A total of 11,585 participants were recruited from the Beijing Health Management Cohort during the period 2012-2016. We evaluated whether hyperuricemia was associated with NAFLD development (part I) and whether NAFLD was associated with hyperuricemia incidence (part II) using a logistic regression model. Further, the cross-lagged panel analysis model was used to simultaneously examine the bidirectional relationship between hepatic steatosis and serum uric acid (SUA) (part III). Subgroup and interaction analyses were also performed to assess whether other variables moderated those relationships.
In part I, multiple logistic regression indicated that baseline hyperuricemia was associated with the development of NAFLD (OR = 1.5970, p < 0.0001). In part II, multiple logistic regression showed that baseline NAFLD was not correlated with hyperuricemia incidence (OR = 0.8600, p = 0.1976). In part III, cross-lagged panel analyses indicated that the standard regression coefficient of baseline SUA to follow-up hepatic steatosis (0.1516) was significantly greater than the coefficient from the baseline hepatic steatosis to follow-up SUA (-0.0044) with p < 0.0001 for the difference. This indicated a unidirectional relationship from baseline SUA to follow-up hepatic steatosis, suggesting hyperuricemia may precede NAFLD; and this relationship was not affected by age, sex, dyslipidemia, metabolism syndrome, diabetes but was moderated by abdominal obesity.
This study demonstrated a unidirectional relationship from hyperuricemia to NAFLD incidence, and suggested that lowering SUA levels in hyperuricemia patients may prevent subsequent NAFLD.
高尿酸血症与非酒精性脂肪性肝病(NAFLD)之间的时间关系仍存在争议。本研究旨在探讨两者之间是否存在双向或时间关系。
本研究共纳入了 2012 年至 2016 年期间北京健康管理队列中的 11585 名参与者。我们使用逻辑回归模型评估了高尿酸血症是否与 NAFLD 进展(第一部分)相关,以及 NAFLD 是否与高尿酸血症的发生相关(第二部分)。进一步使用交叉滞后面板分析模型同时检验了肝脂肪变性和血清尿酸(SUA)之间的双向关系(第三部分)。还进行了亚组和交互分析,以评估其他变量是否调节这些关系。
在第一部分中,多变量逻辑回归表明基线高尿酸血症与 NAFLD 的发生相关(OR=1.5970,p<0.0001)。在第二部分中,多变量逻辑回归表明基线 NAFLD 与高尿酸血症的发生率无关(OR=0.8600,p=0.1976)。在第三部分中,交叉滞后面板分析表明,基线 SUA 对随访肝脂肪变性的标准回归系数(0.1516)显著大于基线肝脂肪变性对随访 SUA 的系数(-0.0044),差异具有统计学意义(p<0.0001)。这表明从基线 SUA 到随访肝脂肪变性存在单向关系,提示高尿酸血症可能先于 NAFLD 发生;这种关系不受年龄、性别、血脂异常、代谢综合征、糖尿病的影响,但受腹型肥胖的调节。
本研究表明,高尿酸血症与 NAFLD 发生率之间存在单向关系,提示降低高尿酸血症患者的 SUA 水平可能预防随后发生的 NAFLD。