Abstract
Background and aims
Occult hepatitis B virus infection (OBI) poses a challenge to the safety of blood donation. The prevalence of OBI is not well documented in Indonesia, although this information in such an endemic country is needed. This study was aimed to evaluate the prevalence of occult hepatitis B in blood donors from two cities of Indonesia, and to study the genetic variation and its effect on the predicted antigenicity of HBsAg.
Methods
Serum samples of 309 regular blood donors negative for HBsAg were tested for anti-HBs and anti-HBc. Hepatitis B virus (HBV) DNA isolated from anti-HBc-positive samples were analyzed by polymerase chain reaction, cloned and sequenced. Antigenic properties of identified HBsAg mutants were predicted by calculation of the antigenic index.
Results
Of the 309 HBsAg-negative samples, anti-HBc was positive in 134 (43.4%) and HBV DNA was detected in 25 (8.1%). Seven of the viremic samples had nucleotide substitutions (A521G, A551T, C582T, and A562G) in the S gene, causing amino acid mutations (T123A, M133L, and T143M) in the ‘a’ determinant of HBsAg that resulted in changes in the predicted antigenicity.
Conclusions
OBI was detected in blood donors’ samples in Indonesia. Anti-HBc was shown to be a better screening parameter than HBsAg, however, it might result in the loss of donors particularly in endemic countries. HBsAg detection failure in this study might be due to mutations altering the protein antigenicity and/or the low-level carriage of HBV.
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References
World Health Organization. Hepatitis B vaccines: weekly epidemiological record. WHO annual report. Switzerland; 2009, 84:405–420
Liaw YF, Leung N, Kao JH, Piratvisuth T, Gane E, Han KH, Guan R, Lau GKK, Locarnini S. Asian–Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int 2008;2:263–283
Hoofnagle JH, Seeff LB, Bales ZB, Zimmerman HJ. Type B hepatitis after transfusion with blood containing antibody to hepatitis B core antigen. N Engl J Med 1978;298:1379–1383
Levicnik-Stezinar S, Rahne-Potokar U, Candotti D, Lelie N, Allain JP. Anti-HBs positive occult hepatitis B virus carrier blood infectious in two transfusion recipients. J Hepatol 2008;48:1022–1025
Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M, Craxi A, Donato F, Ferrari C, Gaeta GB, Gerlich WH, Levrero M, Locarnini S, Michalak T, Mondelli MU, Pawlotsky JM, Pollicino T, Prati D, Puoti M, Samuel D, Shouval D, Smedile A, Squadrito G, Trepo C, Villa E, Will H, Zanetti AR, Zoulim F. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol 2008;49:652–657
Allain JP. Occult hepatitis B virus infection: implications in transfusion. Vox Sang 2004;86:83–91
Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis 2002;2:479–486
Manzini P, Girotto M, Borsotti R, Giachino O, Guaschino R, Lanteri M, Testa D, Ghiazza P, Vacchini M, Danielle F, Pizzi A, Valpreda C, Castagno F, Curti F, Magistroni P, Abate ML, Smedile A, Rizzetto M. Italian blood donors with anti-HBc and occult hepatitis B infection. Haematologica 2007;92:1664–1670
Chemin I, Trepo C. Clinical impact of occult HBV infections. J Clin Virol 2005;34(Suppl 1):S15–S21
Okamoto H, Yano K, Nozaki Y, Matsui A, Miyazaki H, Yamamoyo K, Tsuda F, Machida A, Mishiro S. Mutation within the S gene of hepatitis B virus transmitted from mothers to babies immunized with hepatitis B immunoglobulin and vaccine. Pediatric Res 1992;32:264–268
Iizuka H, Ohmura K, Ishijima A, Satoh K, Tanaka T, Tsuda F, Okamoto H, Miyakawa Y, Mayumi M. Correlation between anti-HBc titers and HBV DNA in blood units without detectable HBsAg. Vox Sang 1992;63:107–111
Okamoto H, Nishizawa T. Non-B Non-C Non-G hepatitis virus gene, polynucleotide, polypeptide, virion, method for separating virion, and method for detecting virus; 1992. http://www.freepatentsonline.com/EP1010759.html (with permission)
Takahashi K, Akahane Y, Hino K, Ohta Y, Mishiro S. Hepatitis B virus genomic sequence in the circulation of hepatocellular carcinoma patients: comparative analysis of 40 full-length isolates. Arch Virol 1998;143:2313–2326
Kwok S, Higuchi R. Avoiding false positives with PCR. Nature 1989;339:237–238
Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp 1999;41:95–98
Sastrosoewignjo RI, Omi S, Okamoto H, Mayumi M, Rustam M, Sujudi T. The complete nucleotide sequence of HBV DNA clone of subtype adw (pMND122) from Menado in Sulawesi Island, Indonesia. ICMR Ann 1987;7:51–60.
Mulyanto, Depamede SN, Surayah K, Tsuda F, Ichiyama K, Takahashi M, Okamoto H. A nationwide molecular epidemiological study on hepatitis B virus in Indonesia: identification of two novel subgenotypes, B8 and C7. Arch Virol 2009;154(7):1047–1059
Jameson BA, Wolf H. The antigenic index: a novel algorithm for predicting antigenic determinants. Cabios 1988;4:181–186
Ghany MG, Ayola B, Villamil FG, Gish RG, Rojter S, Vierling JM, Lok AS. Hepatitis B Virus mutants in liver transplant recipients who were reinfected despite Hepatitis B Immune Globulin prophylaxis. Hepatology 1998;27:213–221
Stuvyer LJ, Locarnini SA, Lok A, Richman DD, Carman WF, Dienstag JL, Schinazi RF. The HEP DART IC. Nomenclature for antiviral-resistant human Hepatitis B Virus mutations in the polymerase region. Hepatology 2001;33:751–757
Wang JT, Lee CZ, Chen PJ, Wang TH, Chen DS. Transfusion-transmitted HBV infection in an endemic area: the necessity of more sensitive screening for HBV carriers. Transfusion 2002;42:1592–1517
Khan M, Dong JJ, Acharya SK, Dhagwahdorj Y, Abbas Z, Jafri SMW, Mulyono DH, Tozun N, Sarin SK. Hepatology issues in Asia: perspectives from regional leaders. J Gastroenterol Hepatol 2004;19:S419–S430
Owusu-Ofori S, Temple J, Sarkodie F, Anokwa M, Candotti D, Allain JP. Predonation screening of blood donors with rapid test: implementation and efficacy of a novel approach to blood safety in resource-poor settings. Transfusion 2005;45:133–140
Yotsuyanagi H, Yasuda K, Moriya K, Shintani Y, Fujie H, Tsutsumi T, Nojiri N, Juji T, Hoshino H, Shimoda K, Hino K, Kimura S, Iino S, Koike K. Frequent presence of HBV in the sera of HBsAg-negative, anti-HBc-positive blood donors. Transfusion 2001;41(9):1093–1099
El-Sherif AM, Abou-Shady MA, Al-Hiatmy MA, Al-Bahrawy AM, Motawea EA. Screening for hepatitis B virus infection in Egyptian blood donors negative for hepatitis B surface antigen. Hepatol Int 2007;1:469–470
Hollinger FB. Hepatitis B virus infection and transfusion medicine: science and the occult. Transfusion 2008;48:1001–1026
Niederhauser C, Taleghani BM, Graziani M, Stolz M, Tinguely C, Schneider P. Blood donor screening: how to decrease the risk of transfusion-transmitted hepatitis B virus? Swiss Med Wkly 2008;138(9–10):134–141
Matsumoto C, Tadokoro K, Fujimura K, Hirakawa S, Mitsunaga S, Juji T. Analysis of HBV infection after blood transfusion in Japan through investigation of a comprehensive donor specimen repository. Transfusion 2001;41:878–884.
Ho MS, Mau YC, Lu CF, Huang SF, Hsu LC, Lin SR, Hsu HM. Patterns of circulating hepatitis B surface antigen variants among vaccinated children born to hepatitis B surface antigen carrier and non-carrier mothers: a population-based comparative study. J Biomed Sci 1998;5:355–362
Hou JL, Wang ZH, Cheng JJ, Lin YL, Lau GKK, Sun J, Zhou FY, Waters J, Karayiannis P, Luo KX. Prevalence of naturally occuring surface gene variants of hepatitis B virus in non-immunized surface antigen-negative Chinese carriers. Hepatology 2001;34:1027–1034
Thakur V, Kazim SN, Guptan RC, Hasnain SE, Bartholomeusz A, Malhotra V, Sarin SK. Transmission of G145R mutant of HBV to an unrelated contact. J Med Virol 2005;76:40–46
Carman WF, Zanetti AR, Karayiannis P, Waters J, Manzillo G, Tanzi E, Zuckerman AJ, Thomas HC. Vaccine-induced escape mutant of hepatitis B virus. Lancet 1990;336:325–329
Seddigh-Tonekaboni S, Waters JA, Jeffers S, Gehrke R, Ofenloch B, Horsch A, Hess G, Thomas HC, Karayiannis P. Effect of variation in the common “a” determinant on the antigenicity of hepatitis B surface antigen. J Med Virol 2000;60:113–121
Zuckerman AJ. Effect of hepatitis B virus mutants on efficacy of vaccination. Lancet. 2000;355:1382–1383
Radziwill G, Tucker W, Schaller H. Mutational analysis of the hepatitis B virus P gene product: domain structure and RNase H activity. J Virol 1990;64(2):613–620
Torresi J, Earnest-Silveira L, Civitico G, Walters TE, Lewin SR, Fyfe J, Locarnini SA, Manns M, Trautwein C, Bock TC. Restoration of replication phenotype of lamivudine-resistant hepatitis B virus mutants by compensatory changes in the “Fingers” subdomain of the viral polymerase selected as a consequence of mutations in the overlapping S gene. Virology 2002;299:88–99
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An erratum to this article can be found at http://dx.doi.org/10.1007/s12072-010-9212-4
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Thedja, M.D., Roni, M., Harahap, A.R. et al. Occult hepatitis B in blood donors in Indonesia: altered antigenicity of the hepatitis B virus surface protein. Hepatol Int 4, 608–614 (2010). https://doi.org/10.1007/s12072-010-9203-5
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DOI: https://doi.org/10.1007/s12072-010-9203-5