Chapter 8
Molecular Variants of Hepatitis B Surface Antigen (HBsAg)
Seyed Mohammad Jazayeri,
Seyed Moayed Alavian,
Payam Dindoost,
Howard C. Thomas,
Peter Karayiannis,
Seyed Mohammad Jazayeri
Hepatitis B Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorSeyed Moayed Alavian
Middle East Liver Diseases Center (MELD), Tehran, Iran
Search for more papers by this authorPayam Dindoost
Middle East Liver Diseases Center (MELD), Tehran, Iran
Search for more papers by this authorHoward C. Thomas
Department of Medicine, Imperial College London, London, UK
Search for more papers by this authorPeter Karayiannis
St George's Medical School, University of Nicosia, Nicosia, Cyprus
Search for more papers by this authorSeyed Mohammad Jazayeri,
Seyed Moayed Alavian,
Payam Dindoost,
Howard C. Thomas,
Peter Karayiannis,
Seyed Mohammad Jazayeri
Hepatitis B Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorSeyed Moayed Alavian
Middle East Liver Diseases Center (MELD), Tehran, Iran
Search for more papers by this authorPayam Dindoost
Middle East Liver Diseases Center (MELD), Tehran, Iran
Search for more papers by this authorHoward C. Thomas
Department of Medicine, Imperial College London, London, UK
Search for more papers by this authorPeter Karayiannis
St George's Medical School, University of Nicosia, Nicosia, Cyprus
Search for more papers by this authorBook Editor(s):Howard C. Thomas BSc, PhD, FRCP, FRCPath, FMedSci,
Anna S.F. Lok MD,
Stephen A. Locarnini MBBS, BSc(Hons), PhD, FRCPath,
Arie J. Zuckerman MD, DSc, FRCP, FRCPath, FMedSci,
Howard C. Thomas BSc, PhD, FRCP, FRCPath, FMedSci
Emeritus Professor of Hepatology, Department of Medicine, Imperial College London, London, UK
Search for more papers by this authorAnna S.F. Lok MD
Alice Lohrman Andrews Research Professor in Hepatology, Director of Clinical Hepatology, Professor of Internal Medicine, Associate Chair for Clinical Research, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA
Search for more papers by this authorStephen A. Locarnini MBBS, BSc(Hons), PhD, FRCPath
Head, Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia
Search for more papers by this authorArie J. Zuckerman MD, DSc, FRCP, FRCPath, FMedSci
Emeritus Professor of Medical Microbiology, Formerly Principal and Dean, Royal Free Hospital School of Medicine
Search for more papers by this authorSummary
The division of hepatitis B virus (HBV) isolated from different geographical regions into genotypes and subtypes has long been recognized. This division is based on amino acid variation in the hepatitis B surface antigen (HBsAg)-encoding region, and more specifically the hydrophilic region that constitutes the a antigenic determinant. This same region constitutes the major neutralizing epitope recognized by natural infection- and vaccine-induced antibodies. However, a number of mutations have been described in different clinical settings that allow the virus to evade the neutralizing immune response. This chapter aims to review the current level of knowledge regarding HBsAg variants.
References
- Neurath AR. Immunohistochemistry of viruses: antigenic structure of human hepatitis virus. Amsterdam: Elsevier Science, 1985.
- Neurath AR, Kent SB, Strick N, et al. Identification and chemical synthesis of a host cell receptor binding site on hepatitis B virus. Cell 1986; 46: 429–436.
- Ashton-Rickardt PG, Murray K. Mutations that change the immunological subtype of hepatitis B virus surface antigen and distinguish between antigenic and immunogenic determination. J Med Virol 1989; 29: 204–214.
- Ashton-Rickardt PG, Murray K. Mutants of the hepatitis B virus surface antigen that define some antigenically essential residues in the immunodominant a region. J Med Virol 1989; 29: 196–203.
- Carman WF, Korula J, Wallace L, et al. Vaccine-induced escape mutant of hepatitis B virus. Lancet 1990; 336: 325–329.
- Brown SE, Stanley C, Howard CR, et al. Affinity of antibody responses in man to hepatitis B vaccine determined with synthetic peptides. Lancet 1984; 2: 184–187.
- Howard CR, Brown SE, et al. Towards the development of synthetic hepatitis B vaccine. In: AJ Zuckerman, editor. Viral hepatitis and liver disease. New York: Alan R Liss, 1988.
- Chen YC, Delbrook K, Dealwis C, et al. Discontinuous epitopes of hepatitis B surface antigen derived from a filamentous phage peptide library. Proc Natl Acad Sci USA 1996; 93: 1997–2001.
- Qiu X, Schroeder P, Bridon D. Identification and characterization of a C(K/R)TC motif as a common epitope present in all subtypes of hepatitis B surface antigen. J Immunol 1996; 156: 3350–3356.
- Magnius LO, Norder H. Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene. Intervirology 1995; 38: 24–34.
- Wallace LCW. Surface gene variation of HBV: scientific and medical relevance. Viral Hepatitis Rev 1997; 3: 12.
- Jazayeri MS, Basuni AA, Sran N, et al. Hepatitis B virus genotypes, core gene variability and ethnicity in the Pacific region. J Hepatol 2004; 41: 139–146.
- Bancroft WH, Mundon FK, Russell PK. Detection of additional antigenic determinants of hepatitis B antigen. J Immunol 1972; 109: 842–848.
- Courouce-Pauty AM, Plancon A, Soulier JP. Distribution of HBsAg subtypes in the world. Vox Sang 1983; 44: 197–211.
- Okamoto H, Omi S, Wang Y, et al. The loss of subtypic determinants in alleles, d/y or w/r, on hepatitis B surface antigen. Mol Immunol 1989; 26: 197–205.
- Cooreman MP, Van Roosmalen MH, Te Morsche R, et al. Characterization of the reactivity pattern of murine monoclonal antibodies against wild-type hepatitis B surface antigen to G145R and other naturally occurring “a” loop escape mutations. Hepatology 1999; 30: 1287–1292.
- Zuckerman AJ. Effect of hepatitis B virus mutants on efficacy of vaccination. Lancet 2000; 355: 1382–1384.
- Oon CJ, Lim GK, Ye Z, et al. Molecular epidemiology of hepatitis B virus vaccine variants in Singapore. Vaccine 1995; 13: 699–702.
- Lee PI, Chang LY, Lee CY, et al. Detection of hepatitis B surface gene mutation in carrier children with or without immunoprophylaxis at birth. J Infect Dis 1997; 176: 427–430.
- Ngui SL, O′Connell S, Eglin RP, et al. Low detection rate and maternal provenance of hepatitis B virus S gene mutants in cases of failed postnatal immunoprophylaxis in England and Wales. J Infect Dis 1997; 176: 1360–1365.
- Basuni AA, Butterworth L, Cooksley G, et al. Prevalence of HBsAg mutants and impact of hepatitis B infant immunisation in four Pacific Island countries. Vaccine 2004; 22: 2791–2799.
- Huang X, Lu D, Ji G, et al. Hepatitis B virus (HBV) vaccine-induced escape mutants of HBV S gene among children from Qidong area, China. Virus Res 2004; 99: 63–68.
- Su HX, et al. High conservation of hepatitis B virus surface genes during maternal vertical transmission despite active and passive vaccination. Intervirology 2011; 54: 122–130.
- Theamboonlers A. Variants within the “a” determinant of HBs gene in children and adolescents with and without hepatitis B vaccination as part of Thailand's Expanded Program on Immunization (EPI). Tohoku J Exp Med 2001; 193: 197–205.
- Tsatsralt-Od B, Takahashi M, Endo K, et al. Prevalence of hepatitis B, C, and delta virus infections among children in Mongolia: progress in childhood immunization. J Med Virol 2007; 79: 1064–1074.
- Hino K, Katoh Y, Vardas E, et al. The effect of introduction of universal childhood hepatitis B immunization in South Africa on the prevalence of serologically negative hepatitis B virus infection and the selection of immune escape variants. Vaccine 2001; 19: 3912–3918.
- Brind A, Jiang JJ, Samuel D, et al. Evidence for selection of hepatitis B mutants after liver transplantation through peripheral blood mononuclear cell infection. J Hepatol 1997; 26: 228–235.
- Carman WF, van Trautwein C, Deursen FJ, et al. Hepatitis B virus envelope variation after transplantation with and without hepatitis B immune globulin prophylaxis. Hepatology 1996; 24: 489–493.
- Ghany MG, Ayola B, Villamil FG, et al. Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis. Hepatology 1998; 27: 213–222.
- Hsu HY, Chang M-H, Liaw S-H, et al. Changes of hepatitis B surface antigen variants in carrier children before and after universal vaccination in Taiwan. Hepatology 1999; 30: 1312–1317.
- Protzer-Knolle U, Naumann U, Bartenschlager R, et al. Hepatitis B virus with antigenically altered hepatitis B surface antigen is selected by high-dose hepatitis B immune globulin after liver transplantation. Hepatology 1998; 254–263.
- Sterneck M, Kalinina T, Otto S, et al. Hepatitis B virus sequence changes evolving in liver transplant recipients with fulminant hepatitis. J Hepatol 1997; 26: 754–764.
- Carman WF, Wallace L, Ward K, et al. Fulminant reactivation of hepatitis B due to envelope protein mutant that escaped detection by monoclonal HBsAg ELISA. Lancet 1995; 345: 1406–1407.
- Yamamoto K, Horikita M, Tsuda F, et al. Naturally occurring escape mutants of hepatitis B virus with various mutations in the S gene in carriers seropositive for antibody to hepatitis B surface antigen. J Virol 1994; 68: 2671–2676.
- Norouzi M, Ghorashi SA, Ataei B, et al. Hepatitis B virus surface antigen variants clustered within immune epitopes in chronic hepatitis B carriers from Hormozgan Province, South of Iran. Iranian J Basic Med Sci 2010; 13: 12.
- Zuckerman JN, Zuckerman AJ. Mutations of the surface protein of hepatitis B virus. Antiviral Res 2003;( 2): 75–78.
- Zanetti AR, Tanzi E, Manzillo G, et al. Hepatitis B variant in Europe. Lancet 1988; 2: 1132–1133.
- Seddigh-Tonekaboni S, Lim WL, Young B, et al. Hepatitis B surface antigen variants in vaccinees, blood donors and an interferon-treated patient. J Viral Hepat 2001; 8: 154–158.
- Nainan OV, Khristova ML, Byun K, et al. Genetic variation of hepatitis B surface antigen coding region among infants with chronic hepatitis B virus infection. J Med Virol 2002; 68: 319–327.
- Cooreman MP, Leroux-Roels G, Paulij WP. Vaccine- and hepatitis B immune globulin-induced escape mutations of hepatitis B virus surface antigen. J Biomed Sci 2001; 8: 237–247.
- Carman WF, Van Deursen FJ, Mimms LT, et al. The prevalence of surface antigen variants of hepatitis B virus in Papua New Guinea, South Africa, and Sardinia. Hepatology 1997; 26: 1658–1666.
- Ho M, Mau Y, Lu C, et al. 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.
- He JW, Lu Q, Zhu QR, et al. Mutations in the ‘a’ determinant of hepatitis B surface antigen among Chinese infants receiving active postexposure hepatitis B immunization. Vaccine 1998; 16: 170–173.
- Alper CA, Kruskall MS, Marcus-Bagley D, et al. Genetic prediction of nonresponse to hepatitis B vaccine. N Engl J Med 1989; 321: 708–712.
- Hsu HY, Chang MH, Ni YH, et al. No increase in prevalence of hepatitis B surface antigen mutant in a population of children and adolescents who were fully covered by universal infant immunization. J Infect Dis 2010; 201: 1192–1200.
- Edstam JS, Dulmaa N, Tsendjav O, et al. Exposure of hepatitis B vaccine to freezing temperatures during transport to rural health centers in Mongolia. Prev Med 2004; 39: 384–388.
- Ogata N, Cote PJ, Zanetti AR, et al. Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus. Hepatology 1999; 30: 779–786.
- Kao JH, Liu CJ, Chen DS. Hepatitis B viral genotypes and lamivudine resistance. J Hepatol, 2002; 36: 303–304.
- Zollner B, Peterson J, Schafer P, et al. Subtype-dependent response of hepatitis B virus during the early phase of lamivudine treatment. Clin Infect Dis 2002; 34: 1273–1277.
- Zollner B, Schafer P, Feucht HH, et al. Correlation of hepatitis B virus load with loss of e antigen and emerging drug-resistant variants during lamivudine therapy. J Med Virol 2001; 65: 659–663.
- Chen WN, Oon CJ. Hepatitis B virus mutants: an overview. J Gastroenterol Hepatol 2002; 17(Suppl): S497–S499.
- Zuckerman JN. Review: hepatitis B immune globulin for prevention of hepatitis B infection. J Med Virol 2007; 79: 919–921.
- Salkic NN. Intrafamilial transmission of hepatitis B: experience and lessons learned in Bosnia and Herzegovina. Hepat Mon 2009; 9: 169–170.
- Lee CY, Huang LM, Chang MH, et al. The protective efficacy of recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers. Pediatr Infect Dis J 1991; 10: 299–303.
- Carman WF. The clinical significance of surface antigen variants of hepatitis B virus. J Viral Hepat 1997; 4(Suppl 1): 11–20.
- Okamoto H, Yano K, Nozaki Y, et al. Mutations within the S gene of hepatitis B virus transmitted from mothers to babies immunized with hepatitis B immune globulin and vaccine. Pediatr Res 1992; 32: 264–268.
- Shi Z, Li X, Ma L, et al. Hepatitis B immunoglobulin injection in pregnancy to interrupt hepatitis B virus mother-to-child transmission: a meta-analysis. Int J Infect Dis 2010; 14: e622–e634.
- Dindoost P, Jazayeri SM, Alavian SM. Hepatitis B immune globulin in liver transplantation prophylaxis: an update. Hepat Mon 2012; 12: 168–176.
- Freshwater DA, Dudley T, Cane P, et al. Viral persistence after liver transplantation for hepatitis B virus: a cross-sectional study. Transplantation 2008; 85: 1105–1111.
- Roche B, Roque-Afonso AM, Sebagh M, et al. Escape hepatitis B virus mutations in recipients of antibody to hepatitis B core antigen-positive liver grafts receiving hepatitis B immunoglobulins. Liver Transpl 2010; 16: 885–894.
- Terrault NA, Zhou S, McCory RW, et al. Incidence and clinical consequences of surface and polymerase gene mutations in liver transplant recipients on hepatitis B immunoglobulin. Hepatology 1998; 28: 555–561.
- Germer JJ, Zein NN, Metwally MA, et al. Characterization of hepatitis B virus surface antigen and polymerase mutations in liver transplant recipients pre- and post-transplant. Am J Transplant 2003; 3: 743–753.
- Kim KH, Lee K, Chang H, et al. Evolution of hepatitis B virus sequence from a liver transplant recipient with rapid breakthrough despite hepatitis B immune globulin prophylaxis and lamivudine therapy. J Med Virol 2003; 71: 367–375.
- Tillmann HL, Trautwein C, Bock T, et al. Mutational pattern of hepatitis B virus on sequential therapy with famciclovir and lamivudine in patients with hepatitis B virus reinfection occurring under HBIg immunoglobulin after liver transplantation. Hepatology 1999; 30: 244–256.
- McMahon G, Ehrlich PH, Moustafa ZA, et al. Genetic alterations in the gene encoding the major HBsAg: DNA and immunological analysis of recurrent HBsAg derived from monoclonal antibody-treated liver transplant patients. Hepatology 1992; 15: 757–766.
- Hawkins AE, Gilson RJ, Gilbert N, et al. Hepatitis B virus surface mutations associated with infection after liver transplantation. J Hepatol 1996; 24: 8–14.
- Shields PL, Owsianka A, Carman WF, et al. Selection of hepatitis B surface “escape” mutants during passive immune prophylaxis following liver transplantation: potential impact of genetic changes on polymerase protein function. Gut 1999; 45: 306–309.
- Terrault N. Management of hepatitis B virus infection in liver transplant recipients: prospects and challenges. Clin Transplant 2000; 14(Suppl 2): 39–43.
- Carman WF, McIntyre G, Klein H. Mutation of HBsAg in homograft recipients receiving hyperimmune globulin. J Hepatology 1992; 16: 59.
- Trautwein C, Schrem H, Tillmann HL, et al. Hepatitis B virus mutations in the pre-S genome before and after liver transplantation. Hepatology 1996; 24: 482–488.
-
Coleman PF,
Chen YC,
Mushahwar IK.
Immunoassay detection of hepatitis B surface antigen mutants.
J Med Virol
1999;
59:
19–24.
10.1002/(SICI)1096-9071(199909)59:1<19::AID-JMV4>3.0.CO;2-B CAS PubMed Web of Science® Google Scholar
- Echevarria JM, Avellon A. Improved detection of natural hepatitis B virus surface antigen (HBsAg) mutants by a new version of the VITROS HBsAg assay. J Med Virol 2008; 80: 598–602.
- Jeantet D, hemin I, Mandrand B, et al. Cloning and expression of surface antigens from occult chronic hepatitis B virus infections and their recognition by commercial detection assays. J Med Virol 2004; 73: 508–515.
- El Chaar M, Candotti D, Crowther RA, A et al. Impact of hepatitis B virus surface protein mutations on the diagnosis of occult hepatitis B virus infection. Hepatology 2010; 52: 1600–1610.
- Hou J, Karayiannis P, Waters J, et al. A unique insertion in the S gene of surface antigen-negative hepatitis B virus Chinese carriers. Hepatology 1995; 21: 273–278.
- Kfoury Baz EM, Zheng J, Mazuruk K, et al. Characterization of a novel hepatitis B virus mutant: demonstration of mutation-induced hepatitis B virus surface antigen group specific “a” determinant conformation change and its application in diagnostic assays. Transfus Med 2001; 11: 355–362.
- Banerjee K, Guptan RC, Bisht R, et al. Identification of a novel surface mutant of hepatitis B virus in a seronegative chronic liver disease patient. Virus Res 1999; 65: 103–109.
- Davaalkham D, Ojima T, Uehara R, et al. Analysis of hepatitis B surface antigen mutations in Mongolia: molecular epidemiology and implications for mass vaccination. Arch Virol 2007; 152: 575–584.
- Norder H, Hammas B, Lofdahl S, et al. Comparison of the amino acid sequences of nine different serotypes of hepatitis B surface antigen and genomic classification of the corresponding hepatitis B virus strains. J Gen Virol 1992; 73: 1201–1208.
- Wallace LA, Echevarria JE, Echevarria JM, et al. Molecular characterization of envelope antigenic variants of hepatitis B virus from Spain. J Infect Dis 1994; 170: 1300–1303.
- Antoni BA, Rodriguez-Crespo I, Gomez-Gutierrez J, et al. Site-directed mutagenesis of cysteine residues of hepatitis B surface antigen. Analysis of two single mutants and the double mutant. Eur J Biochem 1994; 222: 121–127.
- Chiou HL, Lee TS, Kuo J, et al. Altered antigenicity of “a” determinant variants of hepatitis B virus. J Gen Virol 1997; 78: 2639–2945.
- Kohno H, Inoue T, Tsuda F, et al. Mutations in the envelope gene of hepatitis B virus variants co-occurring with antibody to surface antigen in sera from patients with chronic hepatitis B. J Gen Virol 1996; 77: 1825–1831.
- Steward MW, Partidos CD, D'Mello F, et al. Specificity of antibodies reactive with hepatitis B surface antigen following immunization with synthetic peptides. Vaccine 1993; 11: 1405–1414.
- Neurath AR, Strick N, Sproul P, et al. Toleration of amino acid substitutions within hepatitis B virus envelope protein epitopes established by peptide replacement set analysis. I. Region S (139–147). Pept Res 1990; 3: 116–122.
- Hopp TP, Woods KR. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci USA 1981; 78: 3824–3828.
- Stirk HJ, Thornton JM, Howard CR. A topological model for hepatitis B surface antigen. Intervirology 1992; 33: 148–158.
- Chan HL, Hussain M, Lok AS. Different hepatitis B virus genotypes are associated with different mutations in the core promoter and precore regions during hepatitis B e antigen seroconversion. Hepatology 1999; 29: 976–984.
- Yoo BC, Park JW, Kim HJ, et al. Precore and core promoter mutations of hepatitis B virus and hepatitis B e antigen-negative chronic hepatitis B in Korea. J Hepatol 2003; 38: 98–103.
- Ogura Y, Kurosaki M, Asahina Y, et al. Prevalence and significance of naturally occurring mutations in the surface and polymerase genes of hepatitis B virus. J Infect Dis 1999; 180: 1444–1451.
- Oon CJ, Chen WN. Current aspects of hepatitis B surface antigen mutants in Singapore. J Viral Hepat 1998; 5(Suppl 2): 17–23.
- Mu SC, Lin YM, Jow GM, et al. Occult hepatitis B virus infection in hepatitis B vaccinated children in Taiwan. J Hepatol 2009; 50: 264–272.
- Oon CJ, Shiuan K, Keow LG. Identification of hepatitis B surface antigen variants with alterations outside the ‘a’ determinant in immunized Singapore infants. J Infect Dis 1999; 179: 5.
- Chen WN, Oon CJ Lim GK. Frequent occurrence of hepatitis B virus surface antigen mutants in subtype adw in vaccinated Singapore infants. Vaccine 2001; 20: 639–640.
- De Meyer S, Depla E, Maertens G, et al. Characterization of small hepatitis B surface antigen epitopes involved in binding to human annexin V. J Viral Hepat 1999; 6: 277–285.
- Fujiyama A, Miyanohara A, Nozaki C, et al. Cloning and structural analyses of hepatitis B virus DNAs, subtype adr. Nucleic Acids Res 1983; 11: 4601–4610.
- Grethe S, Monazahian M, Böhme I, et al. Characterization of unusual escape variants of hepatitis B virus isolated from a hepatitis B surface antigen-negative subject. J Virol 1998; 72: 7692–7696.
- Zheng X, Weinberger KM, Gehrke R, et al. Mutant hepatitis B virus surface antigens (HBsAg) are immunogenic but may have a changed specificity. Virology 2004; 329: 454–464.
- Chen WN, Oon CJ. Hepatitis B virus surface antigen (HBsAg) mutants in Singapore adults and vaccinated children with high anti-hepatitis B virus antibody levels but negative for HBsAg. J Clin Microbiol 2000; 38: 2793–2794.
- Ireland JH, O'Donnell B, Basuni A, et al. Reactivity of 13 in vitro expressed hepatitis B surface antigen variants in 7 commercial diagnostic assays. Hepatology 2000; 31: 1176–1182.
- Soussan P, Pol S, Garreau F, et al. Vaccination of chronic hepatitis B virus carriers with preS2/S envelope protein is not associated with the emergence of envelope escape mutants. J Gen Virol 2001; 82: 367–371.
- Alavian SM, Miri SM, Jazayeri SM. Hepatitis B vaccine: prophylactic, therapeutic, and diagnostic dilemma. Minerva Gastroenterol Dietol 2012; 58: 167–178.
- Barnaba V, Franco A, Paroli M, et al. Selective expansion of cytotoxic T lymphocytes with a CD4+CD56+ surface phenotype and a T helper type 1 profile of cytokine secretion in the liver of patients chronically infected with hepatitis B virus. J Immunol 1994; 152: 3074–3087.
- Ducos J, Bianchi-Mondain AM, et al. Hepatitis B virus (HBV)-specific in vitro antibody production by peripheral blood mononuclear cells (PBMC) after vaccination by recombinant hepatitis B surface antigen (rHBsAg). Clin Exp Immunol 1996; 103: 15–18.
- Mancini-Bourgine M, Fontaine H, Brechot C, et al. Immunogenicity of a hepatitis B DNA vaccine administered to chronic HBV carriers. Vaccine 2006; 24: 4482–4489.
- Tai PC, Banik D, Lin GI, et al. Novel and frequent mutations of hepatitis B virus coincide with a major histocompatibility complex class I-restricted T-cell epitope of the surface antigen. J Virol 1997; 71: 4852–4856.
- Muhlbacher A, Weber B, Bürgisser P, et al. Multicenter study of a new fully automated HBsAg screening assay with enhanced sensitivity for the detection of HBV mutants. Med Microbiol Immunol 2008; 197: 55–64.
- Roohi A, Yazdani Y, Khoshnoodi J, et al. Differential reactivity of mouse monoclonal anti-HBs antibodies with recombinant mutant HBs antigens. World J Gastroenterol 2006; 12: 5368–5374.
- Scheiblauer H, El-Nageh M, Diaz S, et al. Performance evaluation of 70 hepatitis B virus (HBV) surface antigen (HBsAg) assays from around the world by a geographically diverse panel with an array of HBV genotypes and HBsAg subtypes. Vox Sang 2010; 98: 403–414.
- Weber B, Van der Taelem-Brulé N, Berger A, et al. Evaluation of a new automated assay for hepatitis B surface antigen (HBsAg) detection VIDAS HBsAg Ultra. J Virol Methods 2006; 135: 109–117.
- Bauer T, Weinberger K, Jilg W. Variants of two major T cell epitopes within the hepatitis B surface antigen are not recognized by specific T helper cells of vaccinated individuals. Hepatology 2002; 35: 455–465.
- Schirmbeck R, Dikopoulos N, Kwissa M, et al. Breaking tolerance in hepatitis B surface antigen (HBsAg) transgenic mice by vaccination with cross-reactive, natural HBsAg variants. Eur J Immunol 2003; 33: 3342–3352.
- Chen WN, Oon CJ, Koh S. Horizontal transmission of a hepatitis B virus surface antigen mutant. J Clin Microbiol 2000; 38: 938–939.
- Ho MS, Lu CF, Kuo J, et al. A family cluster of an immune escape variant of hepatitis B virus infecting a mother and her two fully immunized children. Clin Diagn Lab Immunol 1995; 2: 760–762.
- Oon CJ, Chen WN, Goo KS, et al. Intra-familial evidence of horizontal transmission of hepatitis B virus surface antigen mutant G145R. J Infect 2000; 41: 260–264.
- Weber B. Diagnostic impact of the genetic variability of the hepatitis B virus surface antigen gene. J Med Virol 2006; 78: S59–S65.
- Guptan RC, Thakur V, Sarin SK, et al. Frequency and clinical profile of precore and surface hepatitis B mutants in Asian-Indian patients with chronic liver disease. Am J Gastroenterol 1996; 91: 1312–1317.
- Kalinina T, Riu A, Fischer L, et al. A dominant hepatitis B virus population defective in virus secretion because of several S-gene mutations from a patient with fulminant hepatitis. Hepatology 2001; 34: 385–394.
-
Ngui SL,
Hallet R,
Teo CG.
Natural and iatrogenic variation in hepatitis B virus.
Rev Med Virol
1999;
9:
183–209.
10.1002/(SICI)1099-1654(199907/09)9:3<183::AID-RMV248>3.0.CO;2-P CAS PubMed Web of Science® Google Scholar
- Bahn A, Gerner P, Martiné U, et al. Detection of different viral strains of hepatitis B virus in chronically infected children after seroconversion from HBsAg to anti-HBs indicating viral persistence. J Hepatol 1997; 27: 973–978.
- Hsu HY, Chang MH, Ni YH, et al. Surface gene mutants of hepatitis B virus in infants who develop acute or chronic infections despite immunoprophylaxis. Hepatology 1997; 26: 786–791.
- Karthigesu VD, Allison LM, Ferguson M, et al. A novel hepatitis B virus variant in the sera of immunized children. J Gen Virol 1994; 75: 443–448.
- Shahmoradi S, Yahyapour Y, Mahmoodi M, Alavian SM, Fazeli Z, Jazayeri SM. High prevalence of occult hepatitis B virus infection in children born to HBsAg-positive mothers who were non-respondent to hepatitis B vaccination and HBIG. J Hepatol 2012; 57: 515–521.
- Chen WN, Oon CJ, Toh I. Altered antigenicities of hepatitis B virus surface antigen carrying mutations outside the common “a” determinant. Am J Gastroenterol 2000; 95: 1098–1099.
- Alhababi F, Sallam TA, Tong CY. The significance of ‘anti-HBc only’ in the clinical virology laboratory. J Clin Virol 2003; 27: 162–169.
- Carman WF, Owsianka A, Wallace LA, et al. Antigenic characterization of pre- and post-liver transplant hepatitis B surface antigen sequences from patients treated with hepatitis B immune globulin. J Hepatol 1999; 31: 195–201.
- Hoofnagle JH, Waggoner JG. Hepatitis A and B virus markers in immune serum globulin. Gastroenterology 1980; 78: 259–263.
- Katchaki JN, Siem TH, Brouwer R, et al. Detection and significance of anti-HBc in the blood bank; preliminary results of a controlled prospective study. J Virol Methods 1980; 2: 119–125.
- Yoshiba M, Sekiyama K, Sugata F, et al. Post-transfusion fulminant hepatitis B after screening for hepatitis B virus core antibody. Lancet 1992; 339: 253–254.
- Liu CJ, Chen DS, Chen PJ. Epidemiology of HBV infection in Asian blood donors: emphasis on occult HBV infection and the role of NAT. J Clin Virol 2006; 36: S33–S44.
- Mosley JW, Stevens CE, Aach RD, et al. Donor screening for antibody to hepatitis B core antigen and hepatitis B virus infection in transfusion recipients. Transfusion 1995; 35: 5–12.
- Hollinger FB. Hepatitis B virus infection and transfusion medicine: science and the occult. Transfusion 2008; 48: 27.
- Burda MR, Gunther S, Dandri M, et al. Structural and functional heterogeneity of naturally occurring hepatitis B virus variants. Antiviral Res 2001; 52: 125–138.
- Heijtink RA, Van Bergen P, Van Roosmalen MH, et al. Anti-HBs after hepatitis B immunization with plasma-derived and recombinant DNA-derived vaccines: binding to mutant HBsAg. Vaccine 2001; 19: 3671–3680.
- Torresi J, Earnest-Silveira L, Civitico G, et al. 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.
- van Francois G, Damme P, Mphahlele MJ, Meheus A. Mutants hepatitis B viruses: a matter of academic interest only or a problem with far-reaching implications? Vaccine 2001; 19: 17.
- Ogata N, Zanetti AR, Yu M, et al. Infectivity and pathogenicity in chimpanzees of a surface gene mutant of hepatitis B virus that emerged in a vaccinated infant. J Infect Dis 1997; 175: 511–523.
- Sawyer RG, McGory RW, Gaffey MJ, et al. Improved clinical outcomes with liver transplantation for hepatitis B-induced chronic liver failure using passive immunization. Ann Surg 1998; 227: 841–850.
- Samuel D, Muller R, Alexander G, et al. Liver transplantation in European patients with the hepatitis B surface antigen. N Engl J Med 1993; 329: 1842–1847.
- Hollinger FB. Hepatitis B virus genetic diversity and its impact on diagnostic assays. J Viral Hepat 2007; 14: 11–15.
- Cabrerizo M, Bartolome J, Caramelo C, et al. Molecular analysis of hepatitis B virus DNA in serum and peripheral blood mononuclear cells from hepatitis B surface antigen-negative cases. Hepatology 2000; 32: 116–123.
- Weber B, Melchior W, Gehrke R, et al. Hepatitis B virus markers in anti-HBc only positive individuals. J Med Virol 2001; 64: 312–319.
-
Seddigh-Tonekaboni S,
Waters JA,
Jeffers S, et al.
Effect of variation in the common “a” determinant on the antigenicity of hepatitis B surface antigen.
J Med Virol
2000;
60:
113–121.
10.1002/(SICI)1096-9071(200002)60:2<113::AID-JMV2>3.0.CO;2-0 CAS PubMed Web of Science® Google Scholar
- Waters JA, Kennedy M, Voet P, et al. Loss of the common “A” determinant of hepatitis B surface antigen by a vaccine-induced escape mutant. J Clin Invest 1992; 90: 2543–2547.
- Jolivet-Reynaud C, Lesenchal M, O'Donnell B, et al. Localization of hepatitis B surface antigen epitopes present on variants and specifically recognised by anti-hepatitis B surface antigen monoclonal antibodies. J Med Virol 2001; 65: 241–249.
- Hou J, Wang Z, Cheng J, et al. Prevalence of naturally occurring surface gene variants of hepatitis B virus in nonimmunized surface antigen-negative Chinese carriers. Hepatology 2001; 34: 1027–1034.
- Chaudhuri V, Tayal R, Nayak B, et al. Occult hepatitis B virus infection in chronic liver disease: full-length genome and analysis of mutant surface promoter. Gastroenterology 2004; 127: 1356–1371.
- Oon CJ, Chen WN, Goh KT, et al. Molecular characterization of hepatitis B virus surface antigen mutants in Singapore patients with hepatocellular carcinoma and hepatitis B virus carriers negative for HBsAg but positive for anti-HBs and anti-HBc. J Gastroenterol Hepatol 2002; 17: S491–S496.
- Weinberger KM, Bauer T, Böhm S, et al. High genetic variability of the group-specific a-determinant of hepatitis B virus surface antigen (HBsAg) and the corresponding fragment of the viral polymerase in chronic virus carriers lacking detectable HBsAg in serum. J Gen Virol 2000; 81: 1165–1174.
- Moriyama K. Presence of HBV DNA and HBeAg in serum of an anti-HBs-positive individual. Gastroenterology 1989; 97: 1068–1069.
- Moriyama K, Nakajima E, Hohjoh H, et al. Immunoselected hepatitis B virus mutant. Lancet 1991; 337: 125.
- Mimms L. Hepatitis B virus escape mutants: “pushing the envelope” of chronic hepatitis B virus infection. Hepatology 1995; 21: 884–887.
- Carman WF, Dourakis S, Karayiannis P, et al. Incidence of hepatitis B viraemia, detected using the polymerase chain reaction, after successful therapy of hepatitis B virus carriers with interferon-alpha. J Med Virol 1991; 34: 114–118.
- Alexopoulou A, Baltayiannia G, Jammeh S, et al. Hepatitis B surface antigen variant with multiple mutations in the a determinant in an agammaglobulinemic patient. J Clin Microbiol 2004; 42: 2861–2865.
- Lok AS, Hussain M, Cursano C, et al. Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e antigen-negative patients receiving lamivudine therapy. Hepatology 2000; 32: 1145–1153.
- Sheldon J, Soriano V. Hepatitis B virus escape mutants induced by antiviral therapy. J Antimicrob Chemother 2008; 61: 766–768.
- Torresi J, Earnest-Silveira L, Deliyannis G, et al. Reduced antigenicity of the hepatitis B virus HBsAg protein arising as a consequence of sequence changes in the overlapping polymerase gene that are selected by lamivudine therapy. Virology 2002; 293: 305–313.
- Bock CT, Tillmann HL, Torresi J, et al. Selection of hepatitis B virus polymerase mutants with enhanced replication by lamivudine treatment after liver transplantation. Gastroenterology 2002; 122: 264–273.
- Coffin CS, Terrault NA. Management of hepatitis B in liver transplant recipients. J Viral Hepat 2007; 14: 37–44.
- Gane EJ, Angus PW, Strasser S, et al. Lamivudine plus low-dose hepatitis B immunoglobulin to prevent recurrent hepatitis B following liver transplantation. Gastroenterology 2007; 132: 931–937.
- Fujii H, Moriyama K, Sakamoto N, et al. Gly145 to Arg substitution in HBs antigen of immune escape mutant of hepatitis B virus. Biochem Biophys Res Commun 1992; 184: 1152–1157.
- Fernholz D, Stemler M, Brunetto M, et al. Replicating and virion secreting hepatitis B mutant virus unable to produce preS2 protein. J Hepatol 1991; 13: S102–S104.
- Santantonio T, Jung MC, Schneider R, et al. Hepatitis B virus genomes that cannot synthesize pre-S2 proteins occur frequently and as dominant virus populations in chronic carriers in Italy. Virology 1992; 188: 948–952.
- Tai PC, Suk FM, Gerlich WH, et al. Hypermodification and immune escape of an internally deleted middle-envelope (M) protein of frequent and predominant hepatitis B virus variants. Virology 2002; 292: 44–58.
- Yeh CT, Chang MH, Lai HY, et al. Identification of a novel pre-S2 mutation in a subgroup of chronic carriers with spontaneous clearance of hepatitis B virus surface antigen. J Gastroenterol Hepatol 2003; 18: 1129–1138.
- Huy TT, Ushijima H, Win KM, et al. High prevalence of hepatitis B virus pre-s mutant in countries where it is endemic and its relationship with genotype and chronicity. J Clin Microbiol 2003; 41: 5449–5455.
- Sugauchi F, Ohno T, Orito E, et al. Influence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease. J Med Virol 2003; 70: 537–544.
- Melegari M, Bruno S, Wands JR. Properties of hepatitis B virus pre-S1 deletion mutants. Virology 1994; 199: 292–300.
- Xu Z, Yen TS. Intracellular retention of surface protein by a hepatitis B virus mutant that releases virion particles. J Virol 1996; 70: 133–140.
- Chisari FV, Filippi P, Buras J, et al. Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. Proc Natl Acad Sci USA 1987; 84: 6909–6913.
- Lenhoff RJ, Luscombe CA, Summers J. Competition in vivo between a cytopathic variant and a wild-type duck hepatitis B virus. Virology 1998; 251: 85–95.
- Wang HC, Wu HC, Chen CF, et al. Different types of ground glass hepatocytes in chronic hepatitis B virus infection contain specific pre-S mutants that may induce endoplasmic reticulum stress. Am J Pathol 2003; 163: 2441–2449.
- Summers J, Smith PM, Horwich AL. Hepadnavirus envelope proteins regulate covalently closed circular DNA amplification. J Virol 1990; 64: 2819–2824.
- Bartholomeusz A, Locarnini S. Hepatitis B virus mutants and fulminant hepatitis B: fitness plus phenotype. Hepatology 2001; 34: 432–435.
-
Hur GM,
Lee YI,
Suh DJ, et al.
Gradual accumulation of mutations in precore core region of HBV in patients with chronic active hepatitis: implications of clustering changes in a small region of the HBV core region.
J Med Virol
1996;
48:
38–46.
10.1002/(SICI)1096-9071(199601)48:1<38::AID-JMV6>3.0.CO;2-M CAS PubMed Web of Science® Google Scholar
- Fan YF, Lu CC, Chen WC, et al. Prevalence and significance of hepatitis B virus (HBV) pre-S mutants in serum and liver at different replicative stages of chronic HBV infection. Hepatology 2001; 33: 277–286.
- Dong Y, Liu S-L, Zhai X-J, et al. A serological and molecular survey of hepatitis B in children 15 years after inception of the national hepatitis B vaccination program in eastern China. J Med Virol 2009; 81: 1517–1524.
- Fortuin M, Karthigesu V, Allison L, et al. Breakthrough infections and identification of a viral variant in Gambian children immunized with hepatitis B vaccine. J Infect Dis 1994; 169: 1374–1376.
- Ijaz S, Khulan J, Bissett SL, et al. A low rate of hepatitis B virus vaccine breakthrough infections in Mongolia. J Med Virol 2006; 78: 1554–1559.
- Kato H, Nakata K, Hamasaki K, et al. Long-term efficacy of immunization against hepatitis B virus in infants at high-risk analyzed by polymerase chain reaction. Vaccine 1999; 18: 581–587.
- McMahon BJ, Bruden DL, Petersen KM, et al. Antibody levels and protection after hepatitis B vaccination: results of a 15-year follow-up. Ann Intern Med 2005; 142: 333–341.
- Mele A, Tancredi F, Romano L, et al. Effectiveness of hepatiis B vaccination in babies born to hepatitis B surface antigen-positive mothers in Italy. J Infect Dis 2001; 184: 905–908.
- Mu SC, Wang GM, Jow GM, et al. Impact of universal vaccination on intrafamilial transmission of hepatitis B virus. J Med Virol 2011; 83: 783–790.
- Xu L, Wei Y, Chen T, et al. Occult HBV infection in anti-HBs-positive young adults after neonatal HB vaccination. Vaccine 2010; 28: 5986–5992.
- Tsen YJ, Chang MH, Hsu HY, et al. Seroprevalence of hepatitis B virus infection in children in Taipei, 1989: five years after a mass hepatitis B vaccination program. J Med Virol 1991; 34: 96–99.
- Chen HL, Chang MH, Ni YH, et al. Seroepidemiology of hepatitis B virus infection in children: ten years of mass vaccination in Taiwan. JAMA 1996; 276: 906–908.
- Ni YH, Chang MH, Huang LM, et al. Hepatitis B virus infection in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination. Ann Intern Med 2001; 135: 796–800.
- Hsu, HY, et al. Survey of hepatitis B surface variant infection in children 15 years after a nationwide vaccination programme in Taiwan. Gut 2004; 53: 1499–1503.
-
Matsumoto T,
Nakata K,
Hamasaki K, et al.
Efficacy of immunization of high-risk infants against hepatitis B virus evaluated by polymerase chain reaction.
J Med Virol
1997;
53:
255–260.
10.1002/(SICI)1096-9071(199711)53:3<255::AID-JMV13>3.0.CO;2-G CAS PubMed Web of Science® Google Scholar
- Nainan OsC, Taylor PE, Margolis HS. Hepatitis B virus (HBV) antibody resistant mutants among mothers and infants with chronic HBV infection. In: M Rizzetto, JL Gerin, G Verme, editors. Viral hepatitis and liver disease. Turin: Edizioni Minerva Medica, 1997; pp. 132–134.
- Oon CJ, Shiuan K, Keow LG. Identification of hepatitis B surface antigen variants with alterations outside the ′a′ determinant in immunized Singapore infants. J Infect Dis 1999; 179: 5.
- Poovorawan Y, Theamboonlers A, Chongsrisawat V, et al. Molecular analysis of the a determinant of HBsAg in children of HBeAg-positive mothers upon failure of postexposure prophylaxis. Int J Infect Dis 1998; 2: 216–220.
- Velu V, Saravanan S, Nandakumar S, et al. Transmission of “a” determinant variants of hepatitis B virus in immunized babies born to HBsAg carrier mothers. Jpn J Infect Dis 2008; 61: 73–76.
- Zhu CL, Liu P, Chen T, et al. Presence of immune memory and immunity to hepatitis B virus in adults after neonatal hepatitis B vaccination. Vaccine 2011; 29: 7835–7841.
- Avellón A, Echevarría JM, Weber B, et al. European collaborative evaluation of the Enzygnost HBsAg 6.0 assay: performance on hepatitis B virus surface antigen variants. J Med Virol 2011; 83: 95–100.
- Tian Y, Xu Y, Zhang Z, et al. The amino acid residues at positions 120 to 123 are crucial for the antigenicity of hepatitis B surface antigen. J Clin Microbiol 2007; 45: 2971–2978.
- Jia JD, Hong M, Wei L, et al. Multicentre evaluation of the Elecsys hepatitis B surface antigen II assay for detection of HBsAg in comparison with other commercially available assays. Med Microbiol Immunol 2009; 198: 263–269.
- Ly TD, Servant-Delmas A, Bagot S, et al. Sensitivities of four new commercial hepatitis B virus surface antigen (HBsAg) assays in detection of HBsAg mutant forms. J Clin Microbiol 2006; 44: 2321–2326.
- Scheiblauer H, Soboll H, Nick S. Evaluation of 17 CE-marked HBsAg assays with respect to clinical sensitivity, analytical sensitivity, and hepatitis B virus mutant detection. J Med Virol 2006; 78(Suppl 1): S66–S70.
- Lou SC, Pearce SK, Lukaszewska TX, et al. An improved Abbott ARCHITECT((R)) assay for the detection of hepatitis B virus surface antigen (HBsAg). J Clin Virol 2011; 51: 59–63.
- Yuan Q, Ge S, Xiong J, et al. A novel immunoassay for PreS1 and/or core-related antigens for detection of HBsAg variants. J Virol Methods 2010; 168: 108–113.
- La'ulu SL, Roberts WL. The analytic sensitivity and mutant detection capability of six hepatitis B surface antigen assays. Am J Clin Pathol 2006; 125: 748–751.
- Brojer E, Liszewski G, Mikulska M, Allain J-P, Letowska M. The Polish Blood Transfusion Service Viral Study Group, characterization of HBV DNA/HBsAg blood donors in Poland identified by triplex NAT. Hepatology 2006; 44: 9.
- van Roosmalen MH, de Jong JJ, Haenen W, et al. A new HBsAg screening assay designed for sensitive detection of HBsAg subtypes and variants. Intervirology 2006; 49: 127–132.
- Veropalumbo E, Marrone A, Vallefuoco L, et al. Immunocompromised patients with HBsAg a determinant mutants: comparison of HBsAg diagnostic assays. Intervirology 2010; 53: 183–187.
- Villet S, Pichoud C, Villeneuve JP, et al. Selection of a multiple drug-resistant hepatitis B virus strain in a liver-transplanted patient. Gastroenterology 2006; 131: 1253–1261.
- Honorati MC, Facchini A. Immune response against HBsAg vaccine. World J Gastroenterol 1998; 4: 464–466.
