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Background & Aims Occult HBV infection (OBI) is defined by the presence of HBV DNA in the liver and/or serum and negative HBsAg testing. Since the implementation of highly sensitive HBV DNA screening, OBI is also detected in healthy blood donors. The aims of this study were to investigate HBV-specific immune responses and genetic variability in donors with OBI, established by HBV DNA in serum. Methods HBV-specific T-cell responses to HBV antigens were tested in 34 OBI donors by IFN-γ ELISpot, cytometric bead array, and intracellular cytokine staining. As comparison populations, 36 inactive HBV carriers, 22 donors with spontaneously resolved HBV infection, 24 vaccinated donors, and 25 seronegative donors were also included. Surface, pre-S, and pre-c/core genes from 44 genotype D isolates (24 OBI and 20 HBsAg-positive) were sequenced. Results The immune response of OBI donors to the 3 HBV antigens was 29–41%, similar to the response in subjects with resolved HBV infection and higher than that in HBsAg-positive subjects. On sequence analysis, OBI donors presented a higher HBsAg mutation rate than HBsAg-positive subjects. Mutations were clustered in the major hydrophilic region of HBsAg, and no stop codons or relevant mutations that could affect antigen formation or detection were observed. Conclusions Our results suggest that immune response can suppress viral replication to low levels and HBsAg expression to undetectable levels in OBI blood donors. Relevant mutations were not found in the genomic HBsAg coding region. Hence, the fact that HBsAg was not detected in OBI is likely due to low HBsAg production, rather than to a failure of laboratory reagents.

The epidemic of hepatitis C virus (HCV) infection in Europe is continuously evolving and epidemiological parameters (prevalence, incidence, disease transmission patterns and genotype distribution) have changed substantially during the last 15 years. Four main factors contribute to such changes: increased blood transfusion safety, improvement of healthcare conditions, continuous expansion of intravenous drug use and immigration to Europe from endemic areas. As a result, intravenous drug use has become the main risk factor for HCV transmission, prevalent infections have increased and genotype distribution has changed and diversified. Hence, prevalence data from studies conducted a decade ago may not be useful to estimate the current and future burden of HCV infection and additional epidemiological studies should be conducted, as well as new preventive strategies implemented to control the silent epidemic. This review summarizes recently published data on the epidemiology of HCV infection in Europe focusing on the factors currently shaping the epidemic.

The presence and significance of hepatitis C virus infection was evaluated in 241 renal transplant recipients from our hospital. Hepatitis C virus antibodies were tested by second-generation enzyme immunoassay, followed by second- and third-generation immunoblot assays (RIBA-2 and RIBA-3); hepatitis C virus RNA was measured by nested polymerase chain reaction. Hepatitis C virus antibodies, which were detected in 46.5% of patients, were mainly present before transplantation and independently associated with the total amount of transfused blood, time in hemodialysis and duration of posttransplant follow up. Liver dysfunction (alananine aminotransferase elevation) was observed in 50% of antibody-positive recipients, and 92.5% of patients whith chronic liver disease without hepatitis B infection were infected with hepatitis C virus. Most antibody-positive patients (78.4%) tested positive by RIBA-2, but 21.6% were indeterminate; RIBA-3 was positive in 90% of these indeterminates. Hepatitis C virus RNA detection was positive in 96% of antibody-positive cases tested, in 20% of patients who were already anti-HCV negative before transplantation and also demonstrated persistence of HCV infection in all cases who, being antibody positive prior to transplantation, lost these antibodies during follow up (9% of transplanted patients). In conclusion, hepatitis C virus infection is extremely prevalent in renal transplant recipients from Spain and is the main cause of chronic liver disease in these patients. Confirmation by supplemental assays of anti-HCV antibodies is not necessary, but hepatitis C virus RNA testing is indispensable to detect those cases who lose or do not develop hepatitis C virus antibodies.

Background/Aims Chronic hepatitis C patients infected by genotype 1 are the least responsive to combination therapy and therefore monitoring response is important in identifying non-responders quickly, permitting therapy discontinuation and avoiding side effects and costs. We examined the usefulness of measuring total HCV Core Ag in early treatment with peginterferon α-2b and ribavirin in genotype 1 patients in the prediction of response and compared the results with those from HCV RNA quantification. Methods Two hundred and sixty-eight serum samples from 46 genotype 1 patients receiving combination therapy were examined for HCV Core Ag and quantitative HCV RNA. Results At baseline, mean HCV RNA and HCV Core Ag concentrations were significantly lower in sustained virologic responders than in non-responders. The negative predictive value of HCV Core Ag testing in predicting non-response at week 12 is 100%, and for a 2log drop in HCV RNA, using two quantitative tests, it is 88%. Conclusions HCV Core Ag determination allows the identification of non-responders with only one test at week 12 and permits stopping therapy in these patients. HCV Core Antigen testing is cheaper and easier to perform than HCV RNA quantification.

Background/Aims : Hepatitis C has been associated with a decrease in quality of life and with neurological abnormalities. The aim of our study was to investigate the relationship between quality of life and cognitive function. Methods : Quality of life, clinical variables and neuropsychological function were evaluated in 120 patients with hepatitis C (mild chronic hepatitis, compensated cirrhosis and decompensated cirrhosis) and in healthy controls ( n =40, in each group). Results : Patients with chronic hepatitis or compensated cirrhosis showed a decrease in quality of life, in spite of unimpaired neuropsychological tests. Patients with decompensated cirrhosis exhibited a further decrease in quality of life and neuropsychological abnormalities. The decrease in quality of life was associated with the severity of liver failure, neuropsychological abnormalities and treatment with beta-blockers or diuretics. However, in the multivariable analysis, only treatment with beta-blockers or diuretics (which was limited to decompensated cirrhosis) was independently associated with quality of life. Conclusions : Hepatitis C causes a decrease in quality of life even in the absence of major cognitive impairment. The mechanisms that worsen quality of life are unknown. However, in cirrhotic outpatients with prior decompensations, treatment with beta-blockers or diuretics appears to have an important effect on quality of life.

To evaluate the utility of early testing for hepatitis C viremia as a predictor of treatment outcome during interferon or combination therapy.We studied 184 patients with chronic hepatitis C who received interferon and were monitored for HCV RNA. Sixty-two patients received interferon alone for 12 months and 122 patients, who were still HCV RNA positive at 2 months, received an additional 12-month course of interferon and ribavirin combination therapy.Using this strategy, sustained response occurred in a total of 34 patients (18.5%). Independent variables associated with sustained response were HCV genotype (p=0.06), viral loador = 5.1 logs/ml (p= 0.005) and negative HCV RNA at 1 month (p0.0001) in the interferon group, and female sex (p=0.04), genotype (p=0.03), viral loador = 5.5 logs/ml (p=0.01), normal ALT (p=0.001) and decline in viral loador = 1.2 logs/ml after 2 months of interferon monotherapy (p0.001) and negative viremia at 5 months of ribavirin onset (p0.0001) in the combination therapy group. Persistence of viremia at 1 month of interferon monotherapy and at 5 months of combination therapy were the strongest predictors of non-response (negative predictive value of 100% and 99%, respectively).Qualitative assessment of HCV RNA during treatment is the strongest predictor of sustained response during interferon or combination therapy for chronic hepatitis C.

1324 QUASISPECIES HOMOGENIZATION AND IL-28 GENOTYPE (RS12979860 AND RS8099917) MAY FAVOUR SELF-RESOLVING INFECTION AFTER HCV BOTTLENECKING TRANSMISSION M. Cubero, J.I. Esteban, D. Garcia-Cehic, F. Rodriguez-Frias, I. Ortega, E. Domingo, S. Sauleda, M. Bes, A. Sanchez, R. Esteban, J. Guardia, J. Quer. Liver Unit-Department of Internal Medicine, Institut de Recerca (IRVH), Universitat Autonoma Barcelona (UAB), Barcelona, Ciber de Enfermedades Hepaticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Biochemistry Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (IRVH), Universitat Autonoma Barcelona (UAB), Unitat Estadistica Bioinformatica, Institut de Recerca (IRVH), Hospital Universitari Vall d’Hebron, Universitat Autonoma Barcelona (UAB), Barcelona, Biologia Molecular, Centro de Biologia Molecular Severo Ochoa, CSIC-Universidad Autonoma de Madrid, Madrid, Banc de Sang i Teixits, Hospital Universitari Vall d’Hebron, Barcelona, Spain E-mail: mcubero@ir.vhebron.net

H.L. Tillmann1, P. Pradat2, R. Goldin3, P. Merle2, M. Thursz4, J. Langer1, S. Sauleda5, G. Saracco6, S. Badalamenti7, A. Alberti8, J.H. Braconier9, J.I. Esteban5, S. Hadziyannis10, M. Rizzetto6, H.C. Thomas4, M.P. Manns1, C. Trepo2. 1Dpt of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany; 2Dpt of Hepatogastroenterology, Hotel-Dieu, Lyon Cedex, France; 3Department of Histopathology, Imperial College Faculty of Medicine At St Mary’s, London, UK; 4Department of Medicine, Imperial College Faculty of Medicine At St Mary’s, London, UK; 5Hospital General Vall D’ Hebron, Paseo Vall D’ Hebron 119-129, Barcelona, Spain; 6Dpt of Gastroenterology, Azienda Ospedaliera, Torino, Italy; 7Schering-Plough Research Institute, Kenilworth NJ, USA; 8Istituto Di Medicina Clinica E Sperimentale, Padova, Italy; 9Department of Infectious Diseases, University Hospital of Lund, Lund, Sweden; 10Hippokration Hospital, Department of Medicine, Athens, Greece