Increased BMI in Primary Biliary Cirrhosis (PBC) is associated with more advanced fibrosis but the effect of BMI in PSC is unknown. Aim: To examine the effect of BMI on fibrosis stage and progression in PSC. Methods: 291 PSC patients were recruited from the Calgary PSC cohort and stratified according to initial BMI at presentation. BMI <25 as normal, 25-30 as overweight and >30 kg/m2 as obese. Fibrosis stage were measured at least once every 12 months by transient elastography using Fibroscan® and classified as F0 to F4 fibrosis. We examined the fibrosis stage at presentation

and the time in months of progression to the next fibrosis selleck chemicals stage. Data from 1368 patient years of follow up were assessed. Patients with existing cirrhosis at their first presentation

or less than 1 year of follow up data were excluded. Results: 247 cases were eligible for the study. 176 individuals had a normal body weight (BMI <25), 57 were overweight (BMI 25-30) and 14 obese (BMI >30). Mean times of progression to the next fibrosis stage were 51 months, 47 months and 13 months for normal body weight, overweight and obese PSC patients respectively. In addition, obese PSC patients were associated with a more advanced fibrosis stage at presentation compared to normal or overweight cases. Conclusion: Significant proportions of patients with PSC can be classified as overweight or obese. Obesity (BMI 30 kg/m2) in PSC is associated with significantly more advanced fibrosis at presentation and more rapid fibrosis progression as measured by non-invasive

transient elastography. R788 solubility dmso Disclosures: The following people have nothing to disclose: Aliya Gulamhusein, Danielle Reid, Bertus Eksteen BACKGROUND: The pathogenesis of primary sclerosing cholangitis (PSC) is largely unknown due to lack of an ideal animal model. The association of PSC with inflammatory bowel disease suggests a critical role of gut-derived factors in its pathogenesis. Our aim was to investigate the role of small bowel bacterial overgrowth (SBBO) in the development of PSC-like cholangiopathy. Urocanase METHODS: We surgically created a jejunal self-filling blind loop (SFBL) to induce SBBO in a genetically susceptible mouse strain (NOD.B6Abd3), developed by introgression of a 1-Mb non-MHC insulin-dependent diabetes locus from B6 onto NOD background. Control mice underwent laparotomy (sham). Bacterial 16s rRNA gene sequencing was used to analyze bacterial populations of jejunal lumen content. H/E and Trichrome staining were used to assess hepatic inflammation and fibrosis. Flow cytometry was utilized to assess liver immune cell profiles. Chemokine expression was assessed by ELISA (serum) and by RT-PCR (liver tissue). RESULTS: Creation of SFBL led to dramatic increase in bacterial counts in jejunal lumen content, compared to sham mice.