Academia.eduAcademia.edu

P24: Occult hepatitis B infection among vaccinated cohort

2013, Journal of Viral Hepatitis

BACKGROUND: Occult hepatitis B is characterized by undetectable levels of surface antigen, but detectable levels of viral DNA and is becoming a major global threat due to: (i) the effect on the health of children born to carrier mothers despite the presence of passive immunoglobulin at birth (ii) immune escape of current vaccines; and (iii) spread through blood and blood products in post transfusion infection, organ donation, and sexual transmission. The aim of this study is to investigate occult hepatitis B virus among vaccines. METHOD: Four hundred and eight, vaccinee were recruited for this study. All samples were tested for hepatitis B surface antigen, hepatitis B surface and core antibodies using enzyme-linked immunosorbent assay kit (DRG International Inc., USA). Positive samples were re-tested to exclude false positive results. Molecular technique using a nested polymerase chain reaction was done using primers specific to the surface gene. RESULTS: Persistence of hepatitis B surface antibodies (≥10 IU/L) was found in 62.5% (255/408) with 37.5% (153/408) having anti-HBs<10 IU/L in circulation. Hepatitis B core antibodies among vaccinated cohort were found to be 5.0% (20/408). Of which 80% (16/20) of the hepatitis B core antibodies positive, have positive hepatitis B surface antibodies (≥10 IU/L) while 20% (4/20) are negative (<10 IU/L). The former is indicating immunity as a result of previous infection and the latter group are referred to as isolated anti-core, as described in previous studies (1). However none of the samples is hepatitis B surface antigen positive. Hepatitis B viral DNA was detected in all the core antigen positive individuals, contrary to studies in Turkey and Taiwan and in line with other similar studies(2). Occult hepatitis B infections have significant clinical importance since they can become reactivated when the immune system is suppressed and can be transmitted through blood or blood product transfusion, organs transplant, and sexual intercourse. CONCLUSION: The result of this study shows occult chronic HBV infection among adults who were vaccinated against hepatitis B vaccine at infant. The anti-HBs produced were induced by the vaccine they received but do not provide protection against the mutant’s variant suggesting primary infection with mutant’s hepatitis B virus.

30 Poster Sessions P24 Occult hepatitis B infection among vaccinated cohort S Hudu1, Z Sekawi1, N Taib1, Y Malik2 and N Harmal1 1Universiti Putra Malaysia, Selangor, Malaysia, 2. Marusawa H, Uemoto S, Hijikata M, et al. Latent hepatitis B virus infection in healthy individuals with antibodies to hepatitis B core antigen. Hepatology 2000; 31 (2):488–95. 2 P25 Advanced medical devices for HBV genotyping, drug resistance testing and detection of surface antigen mutants using next generation sequencing D Gonzalez1, R Boulme2, C Srichunrusami3, W Chantratita3 and C Sayada2 1Advanced Biological Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, Malaysia BACKGROUND: Occult hepatitis B is characterized by unde- tectable levels of surface antigen, but detectable levels of viral DNA and is becoming a major global threat due to: (i) the effect on the health of children born to carrier mothers despite the presence of passive immunoglobulin at birth; (ii) immune escape of current vaccines; and (iii) spread through blood and blood products in post transfusion infection, organ donation, and sexual transmission. The aim of this study is to investigate occult hepatitis B virus among vaccines. METHOD: Four hundred and eight, vaccinee were recruited for this study. All samples were tested for hepatitis B surface antigen, hepatitis B surface and core antibodies using enzyme-linked immunosorbent assay kit (DRG International Inc., USA). Positive samples were re-tested to exclude false positive results. Molecular technique using a nested polymerase chain reaction was done using primers specific to the surface gene. RESULTS: Persistence of hepatitis B surface antibodies (≥10 IU/L) was found in 62.5% (255/408) with 37.5% (153/408) having anti-HBs <10 IU/L in circulation. Hepatitis B core antibodies among vaccinated cohort were found to be 5.0% (20/408). Of which 80% (16/20) of the hepatitis B core antibodies positive, have positive hepatitis B surface antibodies (≥10 IU/L) while 20% (4/20) are negative (<10 IU/L). The former is indicating immunity as a result of previous infection and the latter group are referred to as isolated anti-core, as described in previous studies (1). However none of the samples is hepatitis B surface antigen positive. Hepatitis B viral DNA was detected in all the core antigen positive individuals, contrary to studies in Turkey and Taiwan and in line with other similar studies (2). Occult hepatitis B infections have significant clinical importance since they can become reactivated when the immune system is suppressed and can be transmitted through blood or blood product transfusion, organs transplant, and sexual intercourse. CONCLUSION: The result of this study shows occult chronic HBV infection among adults who were vaccinated against hepatitis B vaccine at infant. The anti-HBs produced were induced by the vaccine they received but do not provide protection against the mutant’s variant suggesting primary infection with mutant’s hepatitis B virus. REFERENCES 1. Hsu H-Y, Chang M-H, Ni Y-H, et al. Long-Term Follow-up of Children With Postnatal Immunoprophylaxis Failure Who Were Infected With Hepatitis B Virus Surface Antigen Gene Mutant. J Infect Dis 2013; 207(7):1047–57. Laboratories (ABL) S.A., Barcelona, Spain, 2Advanced Biological Laboratories (ABL) S.A., Luxembourg, Luxembourg, 3Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand PURPOSE OF THE STUDY: Despite the potent antiviral activ- ity of approved therapeutic options available for the treatment of chronic hepatitis B (CHB), HBV still persists. Long durations of therapy are required and often lead to the emergence of drug resistance. New insight in HBV drug resistance is starting with the introduction of next generation sequencing (NGS) which identifies major and minor variants within the HBV RT. Specific algorithms managing as well hepatitis B surface antigen (HbSAg) mutants are required for proper disease management and prevention. METHOD: We used DeepChek-HBV, a secured and well-validated software application, in process of CE-IVD marking, to perform within minute automated downstream analysis and HBV resistance interpretation of NGS and Sanger sequencing data. Several clinical guidelines including SeqHepB, the largest HBV drug resistance database, and Geno2pheno, assessed anti-HBV drugs sensitivity levels. Vaccine escape determination through the analysis of HBsAg mutants was included. The genotype of the HBV sequence submitted for analysis was determined by comparison with each of the reference standards using an efficient variant calling system tailored to NGS platforms. Through validation studies in Thailand, Turkey and Netherlands, DeepChek-HBV permitted to harvest key HBV sequences coming from TruGene, ViroSeq, Roche-454 GSJunior and IonTorrent-PGM sequencers. SUMMARY OF RESULTS: In a pool a 19 samples, DeepChekHBV identified three samples (15.8%) and five samples (26.3%) harboring known drug resistance mutations at 20% and 1% thresholds, respectively. Drug resistance susceptibility reductions were observed in 1, 2, 2, 2, 0 samples for Adefovir, Entecavir, Lamivudine, Telbivudine and Tenofovir respectively. CONCLUSION: This study showed the impact of minority variants in drug resistance assessment which still needs to be correlated with clinical utilities. It illustrated the benefits of combining well-validated downstream analysis software and updated knowledge database for managing HBV © 2013 The Authors Journal of Viral Hepatitis © 2013 Blackwell Publishing Ltd, Vol 20 (Suppl. 3), September 2013, 16–42 View publication stats