Serum uric acid to creatinine ratio is associated with higher prevalence of NAFLD detected by FibroScan in the United States.

BACKGROUND: The association between the serum uric acid (sUA) to creatinine ratio (sUA/Cr) and non-alcoholic fatty liver disease (NAFLD) has not been sufficiently clarified. In this study, we investigated the relationship between sUA/Cr and NAFLD among participants in the United States. METHODS: We performed a cross-sectional study based on data from the National Health and Nutrition examination Survey (NHANES) 2017-2018. A measured controlled attenuation parameter (CAP) value of ≥274 dB/m detected by Fibroscan was used to identify hepatic steatosis. SUA/Cr was calculated as sUA divided by serum creatinine. Multivariate logistic regression analysis was used to estimate the association between sUA/Cr and NAFLD. The adjusted odds ratio (OR) of sUA/Cr for NAFLD was estimated, and subgroup analysis stratified by sex was also conducted. The nonlinear relationship between sUA/Cr and NAFLD was further described using smooth curve fittings and threshold-effect analysis. RESULTS: We found that sUA/Cr was positively correlated with NAFLD status after fully adjustment for confounding factors. In subgroup analysis stratified by sex, the positive interaction between sUA/Cr and NAFLD status only existed in women but not in men. Moreover, the nonlinear association between sUA/Cr and NAFLD status was an inverted U-shaped curve with an inflection point at 9.7 among men. CONCLUSIONS: Our study identified that sUA/Cr was positively associated with the risk of NAFLD among individuals in the United States. Moreover, the correlation between sUA/Cr and NAFLD differed according to sex.

Ubiquitously specific protease 4 inhibitor-Vialinin A attenuates inflammation and fibrosis in S100-induced hepatitis mice through Rheb/mTOR signalling.

Inflammation and fibrosis are major consequences of autoimmune hepatitis, however, the therapeutic mechanism remains to be investigated. USP4 is a deubiquitinating enzyme and plays an important role in tissue fibrosis and immune disease. Vialinin A is an extract from mushroom and is a specific USP4 inhibitor. However, there is lack of evidences that Vialinin A plays a role in autoimmune hepatitis. By employing S100-induced autoimmune hepatitis in mice and AML12 cell line, therapeutic mechanism of Vialinin A was examined. Inflammation was documented by liver histological staining and inflammatory cytokines. Fibrosis was demonstrated by Masson, Sirius red staining and fibrotic cytokines with western blot and real-time RT-PCR. In experimental animal, there were increases in inflammation and fibrosis as well as USP4, and which were reduced after treatment of Vialinin A. Vialinin A also reduced Rheb and phosphorylated mTOR. Moreover, in LPS-treated AML12 cells, LPS-induced USP4, inflammatory and fibrotic cytokines, phosphorylated mTOR and Rheb. Specific inhibitory siRNA of USP4 reduced USP4 level and the parameters mentioned above. In conclusion, USP4 was significantly elevated in autoimmune hepatitis mice and Vialinin A reduced USP4 level and attenuate inflammation and fibrosis in the liver. The mechanism may be related to regulation of Rheb/mTOR signalling.