Methods Bile duct ligation (BDL) was performed on wildtype rats, which received

atorvas-tatin (15mg/kg*d) for Protein Tyrosine Kinase inhibitor one week starting at one, two, three, four and five weeks after BDL (T1-T5), while controls remained untreated. Hepatic fibrosis was analyzed by immunohisto-chemistry and hepatic hydroxyproline content. TGFβ levels were measured by RT-PCR. Proteolytic activity of MMP-2 was examined by zymography. Levels of type I, III, IV and VI collagen degradation by MMP activity (C1M, C3M, C4M and C6M) and formation of type III and IV collagen (PRO-C3 and P4NP7S) markers were assessed by specific ELISAs in serum probes. Results Serum markers of ECM neo-epitopes reflected significantly the remodelling of the ECM in the liver and were able to distinguish between early (T1-T3) and severe fibrosis (T4-T5). Statin treatment was associated with significantly lower levels of neo-epitopes, especially when therapy was initiated in the stage of severe fibrosis (T4-T5). Furthermore, the neo-epi-tope markers were correlated to hepatic expression of profi-brotic cytokines TGFb1 and TGFb2. The formation markers PRO-C3 and P4NP7S as well as degradation markers C4M and C6M correlated significantly with

MMP-2 activity in rats with severe fibrosis. Discussion Determination of ECM neo-epitopes in serum allowed us to distinguish between mild and severe fibrosis and to assess ECM remodeling. With respect to the results during BI 6727 statin therapy, neo-epitopes might serve as read-out for efficacy of anti-fibrotic treatment. Disclosures: Diana J. Leeming – Employment: Nordic Bioscience Mette J. Nielsen -Grant/Research Support: Nordic Bioscience A/S Morten A. Karsdal – Stock 上海皓元 Shareholder: Nordic Bioscience The following people have nothing to disclose: Robert Schierwagen, Sabine Klein, Tilman Sauerbruch, Aleksander Krag, Jonel Trebicka BACKGROUND/AIMS:

LOXL2 is a key enzyme that promote-scross-linking of collagen type I and is expected to be a novel therapeutic target for liver fibrosis. The efficacy of LOXL2 inhibitor on panlobular fibrosis has been previously demonstrated in hepatotoxin-induced models, however the efficacy in biliary-type fibrosis is not known. We studied the therapeutic efficacy of a novel anti-LOXL2 monoclonal antibody in two mouse models of primary sclerosis cholangitis (PSC)-like biliary fibrosis. METHODS: We developed an improved mouse model resembling human PSC with rapidly progressive fibrosis and early-onset portal hypertension by backcrossing the Mdr2 mutation on a fibrosis susceptible background (BALB/c). Anti-LOXL2 therapeutic antibody (AB0023mAB, 30mg/kg) or control antibody (M64, 30mg/kg) were administered i.p. twice a week in Mdr2-/-.BALB/c mice (n = 10 per group) from age 4 weeks to 8 weeks, and in C57BL/6 mice fed 3,5- diethoxycarbonyl- 1,4-dihydrocollidine (DDC)- diet for 4 weeks (n=9-11 per group).