Hyperuricemia precedes non-alcoholic fatty liver disease with abdominal obesity moderating this unidirectional relationship: Three longitudinal analyses

Abstract

Background and aims: 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.

Methods: 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.

Results: 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.

Conclusions: This study demonstrated a unidirectional relationship from hyperuricemia to NAFLD incidence, and suggested that lowering SUA levels in hyperuricemia patients may prevent subsequent NAFLD.

Keywords: Bidirectional analysis; Cross-lagged panel analysis; Hepatic steatosis; Hyperuricemia; Non-alcoholic fatty liver disease; Serum uric acid; Temporal relationship.