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

Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
PLoS ONE (Impact Factor: 3.23). 07/2010; 5(7):e11578. DOI: 10.1371/journal.pone.0011578
Source: PubMed


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.

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    • "Studies had shown that uric acid might play an important role in the NAFLD [8–13]. A few cross-sectional studies in Korean adults and in nondiabetic adults from the USA had shown that elevated uric acid level was independently associated with ultrasound-diagnosed NAFLD [14, 15]. "
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    ABSTRACT: Objective: To investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) and the association of serum uric acid level with NAFLD in Uygur people, Xinjiang. Methods: A total of 2241 Uyghur persons (1214 males and 1027 females) were interviewed for physical checkups from 2011 to 2012. The clinical data of questionnaire survey, body mass index (BMI), abdominal circumference, blood pressure, blood sugar, blood lipid, and serum uric acid level were collected for analysis. Results: The prevalence rates of NAFLD determined by abdominal ultrasound examination and hyperuricemia were 43.9% and 8.4%, respectively. The persons with NAFLD had significantly higher serum uric acid levels than those without NAFLD (320 ± 88 versus 254 ± 80 μ mol/L; P < 0.001). The prevalence rate of NAFLD was significantly higher in subjects with hyperuricemia than that in those without hyperuricemia (78.19% versus 40.83%; P < 0.001), and the prevalence rate increased with progressively higher serum uric acid levels (P < 0.001). Multiple regression analysis showed that hyperuricemia was associated with an increased risk of NAFLD (odds ratio (OR): 2.628, 95% confidence interval (CI): 1.608-4.294, and P < 0.001). Conclusion: Serum uric acid level was significantly associated with NAFLD, and the prevalence rate of NAFLD increased with progressively higher serum uric acid levels.
    The Scientific World Journal 01/2014; 2014:393628. DOI:10.1155/2014/393628 · 1.73 Impact Factor
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    • "Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide [1], [2]. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD and can result in cirrhosis and hepatocellular carcinoma [3]–[5]. "
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    ABSTRACT: The human gut microbiota has profound influence on host metabolism and immunity. This study characterized the fecal microbiota in patients with nonalcoholic steatohepatitis (NASH). The relationship between microbiota changes and changes in hepatic steatosis was also studied. Fecal microbiota of histology-proven NASH patients and healthy controls was analyzed by 16S ribosomal RNA pyrosequencing. NASH patients were from a previously reported randomized trial on probiotic treatment. Proton-magnetic resonance spectroscopy was performed to monitor changes in intrahepatic triglyceride content (IHTG). A total of 420,344 16S sequences with acceptable quality were obtained from 16 NASH patients and 22 controls. NASH patients had lower fecal abundance of Faecalibacterium and Anaerosporobacter but higher abundance of Parabacteroides and Allisonella. Partial least-square discriminant analysis yielded a model of 10 genera that discriminated NASH patients from controls. At month 6, 6 of 7 patients in the probiotic group and 4 of 9 patients in the usual care group had improvement in IHTG (P = 0.15). Improvement in IHTG was associated with a reduction in the abundance of Firmicutes (R(2) = 0.4820, P = 0.0028) and increase in Bacteroidetes (R(2) = 0.4366, P = 0.0053). This was accompanied by corresponding changes at the class, order and genus levels. In contrast, bacterial biodiversity did not differ between NASH patients and controls, and did not change with probiotic treatment. NASH patients have fecal dysbiosis, and changes in microbiota correlate with improvement in hepatic steatosis. Further studies are required to investigate the mechanism underlying the interaction between gut microbes and the liver.
    PLoS ONE 04/2013; 8(4):e62885. DOI:10.1371/journal.pone.0062885 · 3.23 Impact Factor
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    • "However, it is also possible that an AMPD product might act as an inhibitor of AMPK activity. One of the downstream products of AMPD is uric acid, which is known to predict both fatty liver and metabolic syndrome [33], [34], [35], [41]. We therefore examined the effect of uric acid on AMPK activity in HepG2 cells. "
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    ABSTRACT: Fatty liver (hepatic steatosis) is associated with nucleotide turnover, loss of ATP and generation of adenosine monophosphate (AMP). It is well known that in fatty liver, activity of the AMP-activated kinase (AMPK) is reduced and that its stimulation can prevent hepatic steatosis by both enhancing fat oxidation and reducing lipogenesis. Here we show that another AMP dependent enzyme, AMPD2, has opposing effects on fatty acid oxidation when compared to AMPK. In human hepatocytres, AMPD2 activation -either by overexpression or by lowering intracellular phosphate levels with fructose- is associated with a significant reduction in AMPK activity. Likewise, silencing of AMPK spontaneously increases AMPD activity, demonstrating that these enzymes counter-regulate each other. Furthermore, we show that a downstream product of AMP metabolism through AMPD2, uric acid, can inhibit AMPK activity in human hepatocytes. Finally, we show that fructose-induced fat accumulation in hepatocytes is due to a dominant stimulation of AMPD2 despite stimulating AMPK. In this regard, AMPD2-deficient hepatocytes demonstrate a further activation of AMPK after fructose exposure in association with increased fatty acid oxidation, and conversely silencing AMPK enhances AMPD-dependent fat accumulation. In vivo, we show that sucrose fed rats also develop fatty liver that is blocked by metformin in association with both a reduction in AMPD activity and an increase in AMPK activity. In summary, AMPD and AMPK are both important in hepatic fat accumulation and counter-regulate each other. We present the novel finding that uric acid inhibits AMPK kinase activity in fructose-fed hepatocytes thus providing new insights into the pathogenesis of fatty liver.
    PLoS ONE 11/2012; 7(11):e48801. DOI:10.1371/journal.pone.0048801 · 3.23 Impact Factor
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