High Serum Uric Acid Increases the Risk for Nonalcoholic Fatty Liver Disease: A Prospective Observational Study

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease, and serum uric acid is observed to be significantly elevated in NAFLD patients. However, whether this elevation is causal, a bystander, or a consequence of NAFLD remains unclear. We performed a population-based prospective study among the employees of Zhenhai Refining & Chemical Company Ltd., Ningbo, China to investigate whether the elevation of serum uric acid has a casual role for NAFLD. A total of 6890 initially NAFLD-free subjects were followed up for 3 years. Overall, 11.80% (813/6890) subjects developed NAFLD over 3 years of follow-up. The cumulative incidence of NAFLD increased with progressively higher baseline serum uric acid levels (the cumulative incidence was 7.2%, 9.5%, 11.5%, 13.8%, and 17.2% in quintile 1, quintile 2, 3, 4 and 5, respectively; P value for trend <0.001). Cox proportional hazards regression analyses showed that serum uric acid levels were independently and positively associated with the risk for incident NAFLD; the age-, gender- and metabolic syndrome adjusted hazard ratio (95% CI) for the subjects in quintile 2, 3, 4 and 5 versus quintile 1 was 1.18 (0.91–1.54), 1.32 (1.03–1.70), 1.39 (1.09–1.78) and 1.50 (1.18–1.92), respectively. Taken together, our prospective observational study showed that elevation of serum uric acid levels independently predicts increase risk for incident NAFLD.

Study of Serum Uric Acid in Chronic Liver Disease and Its Relation With Other Parameters

“…This may be because high UA indicates ongoing hepatocellular destruction. So far, most of the studies on serum UA have been done with NAFLD 10 . In one prospective study from China, they found that hyperuricemia was an independent predictor of development of NAFLD with hazard ratio of 1.62 10 .…”

Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

“…There is a graded, positive association between SUA levels and NAFLD severity and elevated SUA levels predict NAFLD risk independently of coexisting MetS features in different ethnicities. [99][100][101][102][103][104][105][106][107][108] Accordingly, a large study found that increased SUA levels were associated with cirrhosis and elevated serum liver enzymes, independent of potential confounders, in 5,518 participants during a mean follow-up of 12.9 years. 96 Further studies are needed to ascertain whether reducing SUA levels would prevent NAFLD/NASH development and progression.…”

Association of the serum uric acid level with liver histology in biopsy-proven non-alcoholic fatty liver disease

“…Another study also indicated that hypouricemic therapy using allopurinol and benzbromarone significantly ameliorated hepatic steatosis and decreased serum cholesterol levels in a Mongolian gerbil model of NAFLD (19). In fact, a population-based prospective study showed that SUA was significantly associated with the development of NAFLD, suggesting that high SUA levels may have a causal role in the development of NAFLD (9). Similarly, the present study demonstrated that the SUA level was significantly associated with the degree of steatosis from a histological perspective.…”

“…Hyperuricemia was significantly associated with NAFLD, and the prevalence of NAFLD increases with SUA increase (6)(7)(8). Elevation in SUA levels independently predicts an increase in the risk for the incident of NAFLD and suggests that high SUA levels may have a causal role in the development of NAFLD (9). Certain in vitro and in vivo studies in hepatocytes and liver tissue of mice suggest that uric acid stimulated fat synthesis and induced inflammatory cell infiltration in the liver (10,11).…”