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270A AASLD ABSTRACTS HEPATOLOGY, October, 2015 Hans Huber - Consulting: MiNA Therapeutics; Stock Shareholder: Merck & Co Robert Habib - Board Membership: MiNA Therapeutics Ltd; Management Position: MiNA Therapeutics Ltd; Stock Shareholder: MiNA Therapeutics Ltd Pål Sætrom - Patent Held/Filed: MiNA Therapeutics, Ltd; Stock Shareholder: MiNA Therapeutics, Ltd Nagy Habib - Board Membership: EMcision Limited, Omnicyte Limited, Apterna Limited, MiNA Therapeutics Ltd; Patent Held/Filed: EMcision Limited, Omnicyte Limited; Stock Shareholder: EMcision Limited, Omnicyte Limited, Apterna Limited, MiNA Therapeutics Ltd The following authors have nothing to disclose: Kai-Wen Huang, Anjaneyulu Muragundla, Aravindakshan Jayaprakash, Prashant Vadnal, John Rossi 119 Fibrosis is not just fibrosis - Extracellular matrix turnover is markedly different in two types of viral hepatitis, suggesting different fibrotic representations Mette J. Nielsen 1,2 , Morten A. Karsdal 1 , Konstantin Kazankov 3 , Aleksander Krag 2 , Diana J. Leeming 1 , Jacob George 4 , Henning Gronbaek 3 , Detlef Schuppan 5,6 ; 1 Nordic Bioscience A/S, Herlev, Denmark; 2 Department of Gastroenterology and Hepatology, Odense University Hospital, University of Southern Denmark, Odense, Denmark; 3 Department of Medicine V, Aarhus University Hospital, Aarhus, Denmark; 4 Storr Liver Unit, Westmead Millennium Institute, Westmead Hospital and University of Sydney, Sydney, NSW, Australia; 5 Institute of Translational Immunology, University Medical Center, Mainz, Germany; 6 Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA Background and aim: Fibrosis is the result of a dysregulated tissue remodelling leading to excessive and abnormal accumulation of extracellular matrix (ECM). The developmental pattern of fibrosis depends on the underlying aetiology causing the fibrosis such as; portal-portal, portal-central, or central-central septa, albeit the molecular composition and turnover remain to be investigated. In this study we investigated the level of ECM remodelling in two seemingly similar types of viral hepatitis, namely hepatitis B and C. Methods: In a cross-sectional study design, specific protein fragments of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3 and P4NP7S) were assessed in plasma from 403 chronic hepatitis C patients and 197 chronic hepatitis B patients by specific ELISAs. The grade of inflammation and fibrosis was scored according to the Metavir Activity and Fibrosis Scoring systems based on liver biopsy. Results: Plasma levels of P4NP7S, C3M, C4M, and C6M were significantly elevated in HBV compared to HCV (p
HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 271A 121 Objective Determination of Hepatitis B Phenotype using Biochemical and Serological Markers: Immune Tolerant, Immune Active, Inactive Carrier and Indeterminant Status Adrian M. Di Bisceglie 1 , Manuel Lombardero 2 , Jeffrey Teckman 1 , Lewis R. Roberts 3 , Harry L. Janssen 4 , Steven H. Belle 2 , Jay H. Hoofnagle 5 ; 1 Saint Louis University, St. Louis, MO; 2 University of Pittsburgh, Pittsburgh, PA; 3 Mayo Clinic, Rochester, MN; 4 University of Toronto, Toronto, ON, Canada; 5 NIH, Bethesda, MD Background: HBV infection is frequent world-wide and may result in progressive liver disease or HCC. Effective therapies are available but treatment is usually reserved for patients (pts) with selected biochemical and serological profiles (phenotypes). Currently, criteria for defining HBV phenotype are not standardized and are based upon expert opinion rather than medical evidence. Aim: To determine the distribution of phenotypes in a large cohort of North American pts with chronic HBV infection using standardized definitions and calculation. Methods: Epidemiologic, demographic, biochemical and virologic features of pts enrolled into the HBRN Cohort Study at 19 US and 1 Canadian site were analyzed, assigning pts into 1 of 4 phenotypes: immune tolerant (IT), chronic hepatitis B with (CHB e+) or without HBeAg (CHB e-) or inactive carrier (IC) based upon baseline HBV DNA and ALTs. Cut-off HBV DNA values used to define phenotypes were 10 4 IU/ml for e-negative and 10 5 for e-positive pts. ALT cut-offs were analyzed using either fixed values (30 U/L for men, 20 U/L for women) or using each local lab ULN. Pts not fitting into a phenotype were designated “Indeterminant”. Independently, local investigators assigned a phenotype at baseline based on available laboratory values and clinical impression. Results: 1398 adults (51% male, 71% Asian) had data needed to determine phenotype. The table shows the distribution of phenotypes calculated by two methods of assessing ALT and physician assessment. Only moderate agreement was found between clinician-determined and calculated phenotype using fixed ALTs (Kappa 0.39, 95% CI 0.36-0.42). Of note, only 13% of pts were designated Indeterminant by clinicians compared to 20-40% by computer calculation. Using the Fixed ALT groups for comparison, IT was most distinct, being generally younger, more frequently Asian and female. The most frequent clinical phenotype identified was Indeterminant, the majority of whom (83%) had elevated ALT values despite low levels of HBV DNA, not apparently associated with higher BMI, alcohol consumption or HBV genotype. Clinician estimates often differed from the calculated phenotype. Conclusions: The clinical significance of HBV phenotypes using these standardized definitions requires further study based on long term follow up of these patient cohorts but there is clearly a need to re-examine categorization of pts with chronic HBV infection to more accurately predict their outcomes and need for therapy. Disclosures: Adrian M. Di Bisceglie - Advisory Committees or Review Panels: Gilead, AbbVie, Novartis, Bayer, BTG; Grant/Research Support: Gilead, AbbVie Jeffrey Teckman - Consulting: Dicerna, Isis Pharmaceuticals, Vertex, Proteostasis, Genkyotex, The Alpha-1 Project, Retrophin, RxCelerate, Velgene; Grant/ Research Support: Alnylam, Arrowhead, Alpha-1 Foundation, Gilead Lewis R. Roberts - Grant/Research Support: Bristol Myers Squibb, ARIAD Pharmaceuticals, BTG, Wako Diagnostics, Inova Diagnostics, Gilead Sciences, Five Prime Therapeutics Harry L. Janssen - Consulting: AbbVie, Bristol Myers Squibb, GSK, Gilead Sciences, Innogenetics, Merck, Medtronic, Novartis, Roche, Janssen, Medimmune, ISIS Pharmaceuticals, Tekmira; Grant/Research Support: AbbVie, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Merck, Medtronic, Novartis, Roche, Janssen, Medimmune The following authors have nothing to disclose: Manuel Lombardero, Steven H. Belle, Jay H. Hoofnagle 122 Length of antiviral therapy and cirrhosis are key factors in the development of hepatocellular carcinoma among U.S. veterans with chronic hepatitis B Gina Choi, Marina Serper, David E. Kaplan, Kimberly A. Forde; Gastroenterology, University of Pennsylvania, Philadelphia, PA Background: The risk of hepatocellular carcinoma (HCC) and the effect of anti-viral therapy in U.S. populations with chronic hepatitis B (HBV) is poorly defined. Aim: To examine the incidence and impact of anti-viral therapy on the development of HCC among a national cohort of veterans with chronic HBV. Methods: A retrospective cohort study using the VA Corporate Data Warehouse was performed between 1999-2013. The primary exposure variable was antiviral therapy, defined as ≥6 months of therapy with oral nucleosides. Additional covariates such as demographics and clinical variables such as cirrhosis, alcohol abuse, dyslipidemia, hepatitis C (HCV), and HIV were obtained. Multivariable Cox proportional hazard models were used to evaluate associations between exposures and the primary outcome of HCC. Results: A total of 26,704 veterans had a HBsAg+ result; N=9001 were confirmed to have chronic HBV. The median follow-up time was 7.6 years (IQR 4.2–10.9). Patients were predominantly male (96%), white (45%) and middle aged (M=51, SD 11). A total of 20% had HCV, 7% had HIV, and 23% had alcohol abuse. The prevalence of dyslipidemia was 52%; 13% had cirrhosis. The overall incidence of HCC was 5.6 per 1000 person-years; 26 per 1000 person-years with cirrhosis and 1.9 per 1000 person-years without cirrhosis. The median exposure time of antiviral therapy was 3.6 years (IQR 1.4-7.1). A total of 38% (N=3333) received antiviral therapy for ≥6 months; 23% received ≥3 years and 16% received therapy for ≥5 years. In multivariable models adjusted for age, race, cirrhosis, alcohol abuse, and dyslipidemia, antiviral therapy ≥5 years was associated with decreased incidence of HCC (HR 0.77, 95% CI 0.60-0.98, p=0.03), whereas ≥4 years of antiviral therapy was not protective (HR 1.04, CI 1.03-1.05). Antiviral therapy for ≥5years was associated with a decreased incidence of HCC among cirrhotics (HR 0.56, CI 0.41-0.78, p
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1312A AUTHOR INDEX HEPATOLOGY, Octo
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1366A CATEGORY INDEX HEPATOLOGY, Oc
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