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518A AASLD ABSTRACTS HEPATOLOGY, October, 2015 iary expression of SCT/SR/CFTR/AE2 compared to WT. SCT levels in biliary supernatants was decreased, but increased in serum in dnTGFβRII mice compared to WT, suggesting that SCT comes from other sources such as S cells. There was increased fibrosis and SCT/SR/CFTR/AE2 in early stage PBC samples, but decreased expression of SCT/SR/CFTR/AE2 in advanced PBC samples compared to controls. SCT levels increased in serum but decreased in bile in PBC compared to control. Conclusion: Loss of biliary bicarbonate secretion may contribute to disease progression, which may be partly counteracted by peripheral sources of SCT. Disclosures: The following authors have nothing to disclose: Lindsey Kennedy, Shannon S. Glaser, Francesca Bernuzzi, Fanyin Meng, Julie Venter, Heather L. Francis, Domenico Alvaro, M. Eric Gershwin, Antonio Franchitto, Paolo Onori, Sharon DeMorrow, Marco Marzioni, Eugenio Gaudio, Pietro Invernizzi, Gianfranco Alpini 622 Colectomy is associated with development of hepatobiliary malignancy but not cholangiocarcinoma in patients with Primary Sclerosing Cholangitis. Kate D. Williamson 1,2 , Ladislav Kozak 3 , Said Al Mamari 1 , John Halliday 1,2 , Roger W. Chapman 1,2 ; 1 Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom; 2 Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; 3 Department of Sociology, University of Oxford, Oxford, United Kingdom Introduction: Primary Sclerosing Cholangitis (PSC) is associated with increased risk of malignancy – including hepatobiliary malignancies and colorectal cancer. Colectomy is often performed in patients due to either active inflammatory bowel disease (IBD) or development of dysplasia or colorectal cancer. Recently, the Mayo Clinic in US presented an abstract demonstrating an association between colectomy in PSC patients and the development of cholangiocarcinoma (CCA). We sought to validate this association. Methods: A database of 272 patients with PSC exists at John Radcliffe Hospital, Oxford UK, containing information on baseline demographics and clinical course. We performed a Cox regression analysis to identify variables associated with development of firstly CCA, and secondly any hepatobiliary malignancy (hepatocellular cancer, gallbladder cancer, other cancers arising within the liver, and cholangiocarcinoma). Variables examined were age at PSC diagnosis, gender, presence of IBD, and whether the patient underwent colectomy (including whether the indication was for active disease or for a composite of dysplasia or colorectal cancer). Results: Data were available for 228 patients. Median age at PSC diagnosis was 46.3 years (12.5 – 83.2y), and 61% were male. 4/228 (1.8%) had PSC/overlap with autoimmune hepatitis and were included in the analysis. The median follow up was 8.9 years (0.1 – 29.9y). 13/228 (5.7%) had a diagnosis of CCA, whilst 6 had a diagnosis of an alternative hepatobiliary malignancy, hence 19/228 (8.3%) had a diagnosis of any hepatobiliary malignancy. 18/19 patients with any hepatobiliary malignancy diagnosis had died at time of last follow up. 18% patients had undergone a colectomy, the indication being dysplasia or cancer in 15% cases. On multivariate Cox proportional hazard models, presence of IBD, age at PSC diagnosis and gender were not associated with development of CCA, nor the composite endpoint of any hepatobiliary malignancy. Likewise, colectomy was not associated with development of CCA (HR 0.71, 95%CI 0.15-3.35, p=ns). However, colectomy was associated with development of any hepatobiliary malignancy (HR of 70.39, 95% CI 4.00-1238.52, p
HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 519A <strong>studies</strong> in PSC. Furthermore, ALP may be an important factor to include in prognostic modeling for PSC. Disclosures: Ulrich Beuers - Consulting: Intercept via University of Amsterdam, Novartis via University of Amsterdam; Grant/Research Support: Falk, Zambon; Speaking and Teaching: Falk Foundation, Gilead, Roche, Shire Cyriel Y. Ponsioen - Advisory Committees or Review Panels: Takeda; Consulting: AbbVIE; Grant/Research Support: AbbVIE, Schering Plough, Dr. Falk Pharma, Tramedico Netherlands, Takeda The following authors have nothing to disclose: Elisabeth M. de Vries, Junfeng Wang, Mariska M. Leeflang, Kirsten Boonstra, Ronald Geskus Diagnostic Performance of Serum Fibrosis Markers in PSC 624 Validation of serum fibrosis marker panels in patients with primary sclerosing cholangitis (PSC) in a randomized trial of simtuzumab Christopher L. Bowlus 1 , Keyur Patel 2 , Indra Neil Guha 3 , Roger W. Chapman 4 , Olivier Chazouillères 5 , Naga P. Chalasani 6 , John M. Vierling 7 , Robert P. Myers 8 , Dora Ding 8 , Raul E. Aguilar Schall 8 , Mani Subramanian 8 , John G. McHutchison 8 , Andrew J. Muir 2 , Zachary D. Goodman 9 , Cynthia Levy 10 ; 1 University of California at Davis, Sacramento, CA; 2 Duke Clinical Research Institute, Durham, NC; 3 NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham, United Kingdom; 4 Oxford University, Oxford, United Kingdom; 5 Hôpital Saint Antoine, Paris, France; 6 Indiana University, Indianapolis, IN; 7 Baylor College of Medicine, Houston, TX; 8 Gilead Sciences, Inc., Foster City, CA; 9 Inova Fairfax Hospital, Falls Church, VA; 10 University of Miami, Miami, FL Background: Our objective was to assess the diagnostic performance of serum fibrosis marker panels in patients with PSC. Methods: We calculated FibroTest, ELF, APRI, and FIB-4 and measured serum LOXL2 (sLOXL2) by immunoassay (VIDAS® LOXL2; bioMérieux, Marcy L’Etoile, France) in PSC patients enrolled in a phase 2b trial of simtuzumab. Liver fibrosis was staged according to the Ishak classification and their diagnostic performance for predicting bridging fibrosis (Ishak stages 3-6 vs. 0-2) and cirrhosis (stages 5-6 vs. 0-4) was determined using AUROCs. Sensitivity analyses were conducted according to biopsy length (≥ vs.
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1000A AASLD ABSTRACTS HEPATOLOGY, O
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1312A AUTHOR INDEX HEPATOLOGY, Octo
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1366A CATEGORY INDEX HEPATOLOGY, Oc
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