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

Abstract

Abstract. Hyperuricemia is significantly associated with and independently predicts the risk for non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to examine the association of serum uric acid (SUA) levels with liver histology in patients with biopsy-proven NAFLD. Data were collected from 158 adults aged >18 years, and diagnosed with biopsy-proven NAFLD. The differences in liver histology were assessed between hyperuricemic and normal SUA groups with NAFLD to determine the possible risk factors. The SUA level was closely associated with the degree of steatosis (correlation coefficient 0.177, P= 0.027). A higher proportion of patients with hyperuricemia showed increased severity of lobular inflammation (lobular inflammation score ≥2) compared with patients exhibiting normal SUA (75 vs. 52.7%; χ 2 =8.548, P=0.003). Hyperuricemic groups had higher non-alcoholic steatosis (≥5) compared to the normal SUA groups with NAFLD (48.8 vs. 31.1%; χ 2 =5.131, P=0.024). Hyperuricemia was independently associated with advanced lobular inflammation (odds ratio, 2.79; 95% confidence interval, 1.250-6.257; P= 0.012) using a logistic regression model controlling for ferritin, serum alanine aminotransferase and aspartate aminotransferase. In conclusion, hyperuricemia is associated with histologically severe NAFLD. Hyperuricemia was independently associated with greater odds of advanced lobular inflammation of NAFLD. IntroductionNon-alcoholic fatty liver disease (NAFLD) is a state of intrahepatic fat accumulation, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is the most common liver disease in Western countries, affecting 20-30% of the general population (1). NAFLD is also an emerging public health concern in developing countries (2,3). Among more affluent regions of China, the community prevalence of NAFLD is 15% (2). With the increasing obesity pandemic, the prevalence of NAFLD is likely to increase in the future (2). Serum uric acid (SUA) levels are closely associated with insulin resistance, diabetes mellitus type 2 and metabolic syndrome (4,5). Hyperuricemia was significantly associated with NAFLD, and the prevalence of NAFLD increases with SUA increase (6-8). 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). Therefore, it is plausible that uric acid may reflect increased disease severity in NAFLD. However, there is one previous study regarding the association between UA serum levels and histological severity of NAFLD patients (12). The majority of studies have been conducted in Western populations. Notably, the prevalence of obesity in China is significantly lower compared to Western countries (13,14), and certain features of metabolic ...

Higher Serum Uric Acid Level Predicts Non-alcoholic Fatty Liver Disease: A 4-Year Prospective Cohort Study

“…The first pathogenic mechanism was metabolic disturbances. Oxidative stress and lipid peroxidation were the main causes of fatty liver (36), whereas SUA was the main antioxidant in vivo, which was significantly associated with the degree of steatosis and the greater odds of advanced lobular inflammation of NAFLD (37). Another pathogenic mechanism was IR.…”

Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents

“…shown that hyperuricemia is associated with ALT, LDL-C, fasting glucose and NASH (NAS >5), but mostly was independently associated with greater odds of advanced lobular inflammation of NAFLD and progression to NASH [5]. With regard to this finding [5], recently it has become evident that UA is biologically active and can stimulate the production of inflammatory mediators and a high level of UA also inhibits the bioavailability of endothelial NO causing a reduction of the vasodilatation [32]. Thus, it is plausible that uric acid may influence risk of NASH by promoting liver inflammation and affecting liver microvascular responses.…”

“…Risk factors for liver disease progression and the development of NASH are oxidative stress, systemic inflammation and insulin resistance [4]. Several studies in adults, have shown that hyperuricaemia is associated with insulin resistance (IR), type 2 diabetes (T2DM), MetS and NAFLD but whether hyperuricaemia is associated with NAFLD in the paediatric population is uncertain [5,6].…”

Uric acid induced hepatocytes lipid accumulation through regulation of miR-149-5p/FGF21 axis

“…Other large populationbased cohort studies also found that high SUA levels are positively associated with risk of NAFLD [24,25]. Histological studies have demonstrated that the SUA levels were significantly associated with histological disease severity of NAFLD [26][27][28]. Moreover, uric acid-lowering therapy by allopurinol significantly alleviated HFD-induced hepatic steatosis in an animal model of NAFLD [29].…”