Since patients with NAFLD have altered intestinal microbiota (IM), there is the potential for altered signaling of the chief TLR4 ligand, gram-negative endotoxin and other IM derived TLR ligands. Aims: 1. To compare hepatic expression of genes involved in TLR signaling between patients with simple steatosis (SS) or nonalcoholic steatohepatitis (NASH) LGK-974 nmr and healthy controls (HC); 2. To determine whether these genes correlate with IM. Methods:
In a cross-sectional study, gene expression (Illumina Whole-Genome DASL HT-assay) was measured in liver tissue obtained from biopsies of 20 patients with SS and 19 with NASH or during live donor hepatectomy (HC: n=24). In a subgroup (6 SS, 9 NASH, 8 HC), the relative
amounts of fecal Bifidobacteria, E. coli, Bacteroides/Prevotella, and Firmicutes MLN0128 were assessed (qPCR). ANOVA with Tukey’s HSD test, Wilcoxon test, and Spearman correlations were applied. Results: Body mass index (BMI) and insulin resistance increased significantly from HC to SS and NASH. Bacteroides/Prevotella were lower in NASH compared to HC [median (IQR)] [0.90 (1.66) vs.3.45 (3.84) % of total bacteria; p=0.012) but not different from SS [3.03 (4.97) %]. Seven genes involved in TLR signaling were differentially expressed (>2.0-fold change, adjusted p<0.05) between NAFLD patients and HC. There were no differences between SS and NASH. Bacteroides/Prevotella (%) were correlated with TLR3, TLR7, and PELI1. When controlling for BMI, this remained significant: TLR3 (r=-0.85, p<0.0001), TLR7 (r=-0.599, p=0.0041), PELI1 (r=0.59, p=0.021). Conclusion: TLR signaling related genes are differentially expressed in NAFLD vs. HC, but expression profiles are similar in SS and NASH. The proportion of Gram-negative Bacteroides/Prevotella in stool was higher in NASH vs. HC and was correlated with the expression of important MCE regulators of TLR signaling. The role of IM in TLR-induced inflammation and insulin resistance in NAFLD warrants further
study. Disclosures: Scott Fung – Advisory Committees or Review Panels: Merck, Vertex; Grant/Research Support: Gilead Sciences, Roche; Speaking and Teaching: Gilead Sciences, BMS The following Comelli, Marialena Mouzaki, Ian McGilvray, Sandra E. Fischer, Johane P. Allard Objective To evaluate cardiovascular benefits of modest alcohol consumption among men with nonalcoholic fatty liver disease (NAFLD). Design Cross-sectional study of 10, 581 consecutive male participants aged 40-69 years undergoing abdominal ultrasonography and carotid artery ultrasonography at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2009 to December 2009. Results There were total 2, 129 men diagnosed with NAFLD, and the mean age of the participants was 52.6 years old.