Anti-inflammatory and especially antifibrotic therapies for NASH are urgently needed.Glucagon-like peptide-1 (GLP-1) enhances Epacadostat glucose-dependent insulin secretion, delays gastric emptying and exhibits other antihyperglycemic actions following its release into the circulation from the gut. We examined the effect of a long-acting GLP-1 agonist exenatide (BYDUREON, BY) on inflammation and fibrosis in models of fibrotic NASH and biliary fibrosis. Methods: BY was administered twice weekly by subcutaneous injection at 0.4or 2 mg per kg BW to Mdr2KO mice from week 7-1 1 of age, and to 8 week old C57BL/6 mice fed a methionine

and choline deficient diet (MCD) for 4 weeks. Hepatic fibrosis was assessed by morphometric analysis of sirius redstained collagen and measurement of hydrox-yproline content. Serum biochemistries were determined by an autoanalyzer, and hepatic inflammation was assessed by semi-quantitative immunohistochemistry. Fibrosis and inflammation related transcript levels were quantified by quantitative realtime polymerase chain reaction (qPCR). Results: In mice on the MCD diet, 0.4 more than 2.0 mg/kg BY causeda significant reduction of hepatic steatosis, inflammation and a 30%reduc-tion in total collagen content compared to untreated

controls.BYsignificantly decreased fibrosis related transcripts such as αSMA, procollagenα1 (I),TGFβ1, TIMP-1, but also of putatively fibrolyticMMP-8,MMP-9 and -13. BY also suppressed inflammation related transcripts such

as learn more CD68, CCL3, and TNFα, and increased (anti-inflammatory) Arg1 transcripts. In Mdr2 -/- mice, 0.4 mg/kg BYsignificantly lowered liver collagen content, decreased MMP-13 but increased Arg1 transcripts. Conclusions: A long-acting GLP-1 agonist which is already in clinical use for treatment of type 2 diabetesreduced parameters of hepatic MCE steatosis, inflammation and fibrosis, without negative effects on weight gain, supporting its usefulness to treat human NASH and liver fibrosis. Disclosures: Detlef Schuppan – Advisory Committees or Review Panels: Aegerion, Eli Lilly, Gilead; Consulting: Boehringer-Ingelheim, Isis, Takeda; Grant/Research Support: Boehringer-Ingelheim The following people have nothing to disclose: Xiao-Yu Wang, Shih-yen Weng, Thomas Klein, Yong Ook Kim Placenta-derived stem cells (PDSCs) have been focused as a cell source for liver regeneration. Emerging evidence provides the anti-fibrotic effect of PDSCs on liver fibrosis. However, underlying mechanisms on the effect of PDSCs on liver fibrogenesis remain unclear. The hedgehog (Hh) signaling pathway orchestrates tissue reconstruction in the damaged liver. Recently, micro (mi) RNA-125b is reported to regulate smoothened (smo), Hh signaling activator. Hence, we hypothesized that miRNA-125b mediated Hh signaling pathway might regulate liver regeneration by PDSCs.