A systematic review and a dose-response meta-analysis of coffee dose and nonalcoholic fatty liver disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is the most predominant chronic liver disease worldwide. Effect of coffee on NAFLD risk and its potential dose-response patterns were explored in the study. DESIGN: PubMed, Web of Science, MEDLINE, Cochrane and Embase were searched up to 10 April 2018. We performed pair-wise meta-analysis of <1 cup per day vs. 1-2 cups per days or >2 cups per day to pool the relative risks (RRs) and corresponding 95% confidence intervals (CIs). And dose-response analysis was used to estimate relationship of NAFLD occurrence with coffee intake. RESULTS: Seven articles were included with 4825 cases and 49,616 non-cases. Compared with <1 cup, 1-2 cups or >2 cups of coffee consumption per day were not significantly associated with NAFLD occurrence, and RR were 0.97 (95% CI: 0.85-1.11) and 0.88 (95%CI: 0.72-1.06). However, the summary RR of the highest versus lowest coffee consumption was 0.94 (95% CI: 0.92-0.97). Dose-response meta-analysis presented a non-linearity curve relationship of coffee and NAFLD occurrence while coffee consumption >3 cups per day reduced NAFLD significantly. CONCLUSION: Coffee intake level more than 3 cups was observed lower risk of NAFLD than <2 cups per day. Although the risk of NAFLD was inversely associated with coffee consumption, while relevance may not be very close and more observational studies would be needed to verify the relationship of coffee and NAFLD.

Sodium butyrate ameliorates S100/FCA-induced autoimmune hepatitis through regulation of intestinal tight junction and toll-like receptor 4 signaling pathway.

BACKGROUND AND AIM: Recent investigation revealed that dysbiosis in the gut flora and disruption of permeability of intestinal barrier are possible causes for the development of autoimmune hepatitis. Supplementation of sodium butyrate has been suggested to protect liver injury from disrupted permeability of small intestine. In current study, we employed S100/Freund's complete adjuvant induced autoimmune hepatitis to investigate therapeutic efficacy of sodium butyrate and its mechanism in the liver and upper small intestine. METHODS: C57BL/6 mice were employed and divided into three groups - control group (n=8), autoimmune hepatitis group (n=12) and autoimmune hepatitis with treatment of sodium butyrate group (n=12). Histological staining and western blot analyses were employed to evaluate liver and upper small intestine morphology and gene expression respectively. RESULTS: The findings revealed that S100/Freund's complete adjuvant caused liver injury and disruption of upper small intestine villi. Sodium butyrate attenuated the injuries and prevented migration of Escherichia coli into the liver. Moreover, the effect of sodium butyrate on protection of injuries of the liver and upper small intestine could be due to inhibition of toll-like receptor 4 signaling pathway, as well as its down-regulation of inflammatory cytokines - interleukin-6 and tumor necrosis factor-a. CONCLUSIONS: Sodium butyrate can prevent liver injury by maintaining the integrity of small intestine and inhibiting inflammatory response in S100/Freund's complete adjuvant induced autoimmune hepatitis.

Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced hepatic steatosis and injury.

Fibroblast growth factor 21 (FGF21) is a hepatokine that regulates glucose and lipid metabolism in the liver. We sought to determine the role of FGF21 in hepatic steatosis in mice exposed to chronic alcohol treatment and to discern underlying mechanisms. Male FGF21 knockout (FGF21 KO) and control (WT) mice were divided into groups that were fed either the Lieber DeCarli diet containing 5% alcohol or an isocaloric (control) diet for 4 weeks. One group of WT mice exposed to alcohol received recombinant human FGF21 (rhFGF21) in the last 5 days. Liver steatosis and inflammation were assessed. Primary mouse hepatocytes and AML-12 cells were incubated with metformin or rhFGF21. Hepatic genes and the products involved in in situ lipogenesis and fatty acid ß-oxidation were analyzed. Alcohol exposure increased circulating levels and hepatic expression of FGF21. FGF21 depletion exacerbated alcohol-induced hepatic steatosis and liver injury, which was associated with increased activation of genes involved in lipogenesis mediated by SREBP1c and decreased expression of genes involved in fatty acid ß-oxidation mediated by PGC1α. rhFGF21 administration reduced alcohol-induced hepatic steatosis and inflammation in WT mice. These results reveal that alcohol-induced FGF21 expression is a hepatic adaptive response to lipid dysregulation. Targeting FGF21 signaling could be a novel treatment approach for alcoholic steatohepatitis.