POSTERS from CHB to newly developed LC and further to older LC and HCC was observed in female but not in male patients (table). Conclusions: Genotype C HBV infection is a key factor of disease progression in females, but less important than gender effect in males. P656 THE ROLE OF SEQUENCE VARIATION IN T-CELL EPITOPES OF THE HEPATITIS B VIRUS (HBV) POLYMERASE AND ENVELOPE PROTEINS IN HBeAg CLEARANCE AND DISEASE PROGRESSION C.-J. Huang1 , C.-Y. Lan1 , F.-Y. Sung1 , C.-L. Lin2 , C.-J. Liu3 , C.-F. Wu1 , M.-W. Yu1 . 1 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, 2 Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, 3 Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan E-mail:
[email protected] Background and Aims: HBeAg seroconversion is a key immunologically-mediated event in the natural history of HBV infection. The mechanisms of this seroconversion remain unclear but T-cell response is believed to be critical. We aimed to identify HBV T-cell epitope sequence variation contained in HBV polymerase/envelope in relation to HBeAg clearance and disease progression. Methods: Study subjects were chosen from a cohort study of 2903 HBsAg-positive men enrolled in 1989–1992 and followed up till 2010. Sequencing of the complete HBV polymerase/envelope region was performed on baseline plasma samples with HBV-DNA levels ≥ 1000 copies/ml, and 575 (80.2% with HBV genotype B, 17.7% with genotype C) men had sequence data. Results: Through systematical analysis of T-cell epitope sequences defined by the Immune Epitope Database in four HBV protein regions, polymerase, pre-S1, pre-S2, and S, we found variation of 96 epitopes that was associated with HBeAg clearance after adjustment for age, including 43 that were common for both HBV genotypes, 37 that were genotype B-dependent, and 16 that were genotype C-dependent. Eighty-five percent HBeAg-related epitopes were located within envelope and most of these were HLA class II-restricted. On the population level, variation of T-cell epitopes explained 40.5% of heterogeneity in HBeAg status for genotype B and 64.6% for genotype C. Carriage of variant epitopes was associated with HBeAg clearance, and some of these variant types also correlated with lower plasma viral load and reduced risk for hepatocellular carcinoma. Conclusions: We identified specific epitopes that may have an important role in T-cell responses involved in HBeAg clearance. P657 IN VIVO MUTAGENIC EFFECT OF RIBAVIRIN ON SUBTYPE 3F HEV QUASISPECIES ISOLATED FROM A PATIENT INFECTED FROM PORK MEAT R. Casillas1 , F. Rodr´ıguez-Frias2,3 , B. M´ınguez1,3 , M. Riveiro1,3 , J. Gregori1,4 , D. Garcia-Cehic1,3 , D. Tabernero2,3 , M. Homs2,3 , M. Blasi2,3 , A. Caballero2 , L. Nieto2 , A. Hundesa5 , R. Girones5 , M. Buti1,3,6 , J. Quer1,3,6 . 1 Liver Unit – Vall d’Hebron Institut de Recerca (VHIR), Hospital Univ. Vall d’Hebron (HUVH), 2 Biochemistry Unit, Virology Unit/Microbiol Dept. HUVH, Barcelona, 3 Centro de Investigaci´ on Biom´edica en Red de Enfermedades Hep´ aticas y Digestivas (CIBEREHD) – Instituto de Salud Carlos III, Madrid, 4 Roche Diagnostics SL, Sant Cugat del Valles, 5 Laboratory of Viruses Contaminants of Water and Food, Microbiology, Biology Faculty, Universitat de Barcelona, 6 Universitat Autonoma de Barcelona, Barcelona, Spain E-mail:
[email protected] Background and Aims: Hepatitis E Virus (HEV) is the main responsible of the acute hepatitis in developed countries. Some
animals, like swine, are reservoirs for HEV and transmission to humans has been reported. We describe a case of acute HEV after pork meat intake and study HEV population variability during Ribavirin (Rbv) treatment. Methods: HEV acute infected patient was treated with Rbv after 14 days of follow-up. We phylogenetically studied an RT-PCR fragment of the ORF2 core gene isolated from patient’s serum samples and from a frozen pork meat. Serum HEV viral population at day 0 (t0), 3 (t3), 9 (t9), 15 (t15) and 49 (t49) of Rbv therapy, were studied by ultra-deep pyrosequencing (UDPS, 454/GS-Junior, Roche). Results: Patient was infected with HEV-subtype-3f, identical to pork meat isolates (consensus sequence and six clones), suggesting possible zoonosis. A total of 26239 sequences were obtained by UDPS from patient samples. Viral load declined from 4.87×105 at t0, to 1.21×103 at t3 and 1.11×102 genome-copies/ml at t9. It was negative at t15 and t49. HEV variability increased from t0 (Pi [Nucleotide Diversity] = 0.0000, 1 haplotype) to t3 (Pi = 0.00081, 15 haplotypes) (35% of substitutions associated to Rbv treatment) and declined at t9 (Pi = 0.00052, 6 haplotypes). Conclusions: Our results suggest that the patient became infected by pork meat intake and that Rbv was mutagenic in vivo causing a temporal increase in variability at day 3. At t9, the mutagenic effect of Rbv was not detected, probably by the viral load decay observed just before resolution of infection. P658 LOW RISK OF HEPATITIS B VIRUS REACTIVATION IN HBsAg NEGATIVE, ANTI-HBc POSITIVE CARRIERS UNDERGOING RITUXIMAB FOR RHEUMATOID ARTHRITIS M. Vigano` 1 , V. Varisco2 , P. Lampertico3 , A. Batticciotto2 , A. Mascheroni4 , P. Gibertini4 , R. Pellerito5 , G. Rovera5 , R. Caporali6 , M. Todoerti6 , M. Covelli7 , A. Notarnicola7 , M. Colombo3 , P. Sarzi-Puttini2 . 1 U.O. Epatologia, Ospedale San Giuseppe, Universit` a degli Studi di Milano, 2 UOC Reumatologia, Ospedale L. Sacco, Milano, 3 Fondazione IRCCS Maggiore Hospital, University of Milan, Milan, 4 UOC DH di Reumatologia, Istituto Ortopedico G. Pini, Milano, 5 UO Reumatologia, Ospedale Mauriziano, Torino, 6 Divisione di Reumatologia, IRCCS Fondazione San Matteo, Universit` a di Pavia, Pavia, 7 Reumatologia Universitaria, AOU Policlinico, Bari, Italy E-mail:
[email protected] Background and Aims: Safety of Rituximab (RTX) in hepatitis B surface antigen (HBsAg) negative/anti-hepatitis B core antigen (anti-HBc) positive patients with Rheumatoid Arthritis (RA) is unknown. Methods: We retrospectively reviewed 306 RA treated with RTX in 5 Italian outpatient rheumatologic Clinics. Complete serological screening for HBV status before RTX was available in 33 HBsAg negative/anti-HBc positive patients who did not undergo antiviral prophylaxis. These patients (73% female, 60 yrs, disease duration 8 yrs, 100% serum HBV DNA negative by PCR assay, 95% anti-HBs positive) have been treated with RTX plus disease-modifying antirheumatic drugs (DMARS). RTX was administered for 3 cycles (range: 1–8) lasting for 22 months (range: 0–62) in 14 patients and ongoing in the remaining cases. Laboratory examinations, including serum HBsAg and serum HBV DNA were assessed every 6 months and whenever ALT flared above the upper limit of normal. Results: During 45 months (range: 12–80) of follow-up, antiHBs titers dropped in 27% (2 patients became seronegative). All but one patient (3%) who showed a slight elevation in serum HBVDNA (44 IU/mL) maintained undetectable HBV DNA. In the latter patient, HBV DNA became detectable 5 months after the first RTX administration, was not associated to either HBsAg seroreversion or ALT flare and was promptly suppressed by lamivudine treatment. Another patient (3%) had an ALT flare that however was not related to HBV reactivation.
Journal of Hepatology 2014 vol. 60 | S215–S359
S287
POSTERS Conclusions: In HBsAg negative/anti-HBc positive RA patients, administration of RTX+DMARS poses a negligible risk of HBV reactivation thereby calling for HBsAg or HBV DNA monitoring, only. P659 HEV SEROPREVALENCE IN 291 PATIENTS WITH CHRONIC LIVER DISEASE IN A GERMAN UNIVERSITY HOSPITAL M. Schulz, E. Schott. Hepatology and Gastroenterology, Charit´e Universit¨ atsmedizin Berlin, Berlin, Germany E-mail:
[email protected] Background and Aims: Hepatitis E virus (HEV) is an emerging zoonotic disease in developed countries. In Europe, HEV seroprevalence ranges from 3.2% to 10%, excluding highly endemic areas such as southern France. In Germany rising numbers of HEV infections have been reported recently. Risk factors for the acquisition of HEV are not well understood. Methods: We screened 291 consecutive patients attending the outpatient department at Charite´ university hospital for HEV seroprevalence. The epidemiological characteristics of the study cohort were analysed. Patients testing positive for anti-HEV were questioned for risk factors with a standardized questionnaire. Results: 62 out of 291 screened patients tested positive for HEVIgG, one tested positive for HEV-IgM without detection of IgG. 12/62 HEV-IgG positive patients were cirrhotic. With a mean age of 56.2 years, HEV positive patients were older than HEV negative patients (48.2), no difference was observed regarding gender. Seroprevalence increased with age from 13.0% in patients from 30 to 39 years to 45.8% in patients from 70 to 79 years. 45.9% of HEV-IgG positive patients had contact to domestic animals, 37.7% had received blood transfusions, and 49.2% had regularly consumed uncooked meat. Table: Frequent underlying diseases of screened patients HEV positive, HEV negative, n (% of positive patients) n (% of negative patients) Number of patients Chronic hepatitis B Chronic hepatitis C Primary biliary cirrhosis Autoimmune hepatitis Alcoholic cirrhosis Non alcoholic steatohepatitis Hepatitis of unknown origin Toxic cholestasis
63 28 (44.4) 7 (11.1) 4 (6.4) 5 (7.9) 4 (6.4) 3 (4.8) 6 (9.5) 0
228 97 (42.5) 42 (18.4) 12 (5.3) 16 (7) 3 (1.3) 39 (17.1) 0 4 (1.8)
Conclusions: HEV seroprevalence was 21.7% in a cohort of patients with chronic liver disease, which is higher than data reported previously in comparable study populations. The high seroprevalence found among elderly patients could be due to a lifelong accumulation of risk of exposure to HEV. The results of this study encourage regular testing for HEV in developed countries in case of liver disease of unknown etiology. P660 THE EFFECT OH HEPATITIS B VIRUS INFECTION ON STEATOSIS IN HEPATITIS C VIRUS COINFECTED PATIENTS: THE BOSTIC STUDY N. Goossens1 , N. Coppola2 , R. Zampino3 , M. Stanzione4 , 7 ¨ , D. Moradpour8 , H. Wedemeyer5 , F. Barrera6 , B. Mullhaupt 9 10 11 D. Semela , N. Semmo , R. Malinverni , M. Heim12 , J. George6 , M. Manns5 , L.E. Adinolfi3 , L. Rubbia-Brandt13 , F. Negro1,13 . 1 Division of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland; 2 Department of Mental Health and Public Medicine, 3 Internal Medicine and Hepatology, 4 Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy; 5 Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; S288
6
Storr Liver Unit, Westmead Millenium Institute, University of Sydney at Westmead Hospital, Sydney, NSW, Australia; 7 Division of Gastroenterology and Hepatology, University Hospital Z¨ urich, Z¨ urich, 8 Division of Gastroenterology and Hepatology, University Hospital Lausanne, Lausanne, 9 Division of Gastroenterology, Kantonsspital St. Gallen, St Gallen, 10 Hepatology, Department of Visceral Surgery and opital Neuchˆ atelois, Neuchˆ atel, Medicine, Inselspital Bern, Bern, 11 Hˆ 12 Division of Gastroenterology and Hepatology, University Hospital Basel, Basel, 13 Division of Clinical Pathology, University Hospital, Geneva, Switzerland, Geneva, Switzerland E-mail:
[email protected] Background and Aims: It remains unclear whether HBV may modify the level of virally-induced steatosis in patients with chronic HCV, especially those with genotype 3a, in HBV/HCV coinfected patients. We examined the influence of coinfection with HBV on prevalence and severity of different types of steatosis (i.e. viral vs metabolic) in chronic HCV. Methods: We retrospectively assessed steatosis prevalence and severity in chronic HBV/HCV coinfected patients with a liver biopsy at time of coinfection. Exclusion criteria were excessive alcohol consumption (>21 and >14 drinks/week in men and women respectively), type 2 diabetes and antiviral therapy at time of liver biopsy. HCV-monoinfected controls were matched according to BMI, HCV viremia and genotype. Results: 78 HBV/HCV coinfected patients and 115 HCV controls were included from 10 international centres. Clinical characteristics of HBV/HCV coinfected patients were: average age: 42 years, males: 68%, average BMI: 25.1 kg/m2 , cirrhotic: 24%, genotype 3 HCV: 26%, undetectable HCV viremia: 2.6%, undetectable HBV viremia: 31%. There was no significant difference in steatosis prevalence between the HBV/HCV coinfected group and the HCV group (42% vs 44%, p = 0.40). When including only HCV genotype 3 patients with BMI < 25 kg/m2 (n = 12 coinfected HBV/HCV) there was no difference in steatosis distribution and severity between coinfected and HCV monoinfected patients (p = 0.28). Conclusions: Based on these preliminary findings from the hitherto largest cohort of HBV/HCV coinfected patients, it appears that HBV is not affecting prevalence and intensity of steatosis in HBV/HCV coinfected patients vs HCV monoinfected patients, even in the subgroup of HCV genotype 3 patients with normal BMI. P661 APRI AND FIB-4 VS HISTOLOGY IN CHB PATIENTS IN TENOFOVIR DISOPROXIL FUMARATE (TDF) CLINICAL TRIALS W.R. Kim1 , T. Berg2 , T. Asselah3 , R. Flisiak4 , S. Fung5 , S. Gordon6 , H.L.A. Janssen5 , P. Lampertico7 , D. Lau8 , J.D. Bornstein9 , R.A. Schall9 , P. Dinh9 , L.J. Yee9 , E.B. Martins9 , S.G. Lim10 , R. Loomba11 , J. Petersen12 , M. Buti13 , P. Marcellin3 . 1 Stanford University School of Medicine, Palo Alto, CA, United States; 2 Universit¨ atsklinik Leipzig, Leipzig, Germany; 3 Hˆ opital Beaujon, Paris, France; 4 Medical University of Bialystok, Bialystok, Poland; 5 University of Toronto, Toronto, ON, Canada; 6 Henry Ford Hospital, Detroit, MI, United States; 7 University of Milan, Milan, Italy; 8 Harvard University, Boston, MA, 9 Gilead Sciences, Inc., Foster City, CA, United States; 10 Yoo Loo Lim School of Medicine, Singapore, Singapore; 11 University of California San Diego, San Diego, CA, United States; 12 IFI Institute for Interdisciplinary Medicine, Asklepios Klinik St Georg, Hamburg, Germany; 13 Hospital General Universitari Vall d’Hebron, Barcelona, Spain E-mail:
[email protected] Background and Aims: Serum non-invasive markers of fibrosis such as the AST to Platelet Ratio Index (APRI) and Fibrosis Index Based on Four Factors (FIB-4) were developed mainly in patients with chronic hepatitis C. We evaluated the performance of these scores in assessing liver fibrosis in chronic hepatitis B (CHB) patients.
Journal of Hepatology 2014 vol. 60 | S215–S359