Abstract
Amino acid substitutions within the S gene involving the major antigenic a determinant of the hepatitis B virus (HBV) surface antigen (HBsAg) have been detected in cases of failure of immunization against the virus. Our report showed development of clinical hepatitis in presence of antibody to HBsAg in a healthy individual. A single amino acid substitution (G145R) within the a determinant of the HBsAg was determined by sequencing of the isolated HBV strain. Lamivudine treatment efficiently cleared the peripheral HBV DNA, HBsAg, and hepatitis B e antigen. In conclusion, the immune escape mutant in the S gene can cause hepatitis despite pre-existing naturally acquired immunity.
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Chang JJ, Lewin SR. Immunopathogenesis of hepatitis B virus infection. Immunol Cell Biol 2007;85:16–23.
Okamoto H, Imai M, Tsuda F, Tanaka T, Miyakawa Y, Mayumi M. Point mutation in the S gene of hepatitis B virus for a d/y or w/r subtypic change in two blood donors carrying a surface antigen of compound subtype adyr or adwr. J Virol 1987;61:3030–3034.
Carman WF, Zanetti AR, Karayiannis P, Waters J, Manzillo G, Tanzi E, et al. Vaccine-induced escape mutant of hepatitis B virus. Lancet 1990;336:325–329.
Waters JA, Brown SE, Steward MW, Howard CR, Thomas HC. Analysis of the antigenic epitopes of hepatitis B surface antigen involved in the induction of a protective antibody response. Virus Res 1992;22:1–12.
Chisari FV, Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol 1995;13:29–60.
Fujii H, Moriyama K, Sakamoto N, Kondo T, Yasuda K, Hiraizumi Y, et al. Gly145 to Arg substitution in HBs antigen of immune escape mutant of hepatitis B virus. Biochem Biophys Res Commun 1992;84:1152–1157.
Chiou HL, Lee TS, Kuo J, Mau YC, Ho MS. Altered antigenicity of ‘a’ determinant variants of hepatitis B virus. J Gen Virol 1997;78:2639–2645.
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.
Okamoto H, Yano K, Nozaki Y, Matsui A, Miyazaki H, Yamamoto K, 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.
Oon CJ, Chen WN, Goo KS, Goh KT. Intra-familial evidence of horizontal transmission of hepatitis B virus surface antigen mutant G145R. J Infect 2000;41:260–264.
Chakravarty R, Neogi M, Roychowdhury S, Panda CK. Presence of hepatitis B surface antigen mutant G145R DNA in the peripheral blood leukocytes of the family members of an asymptomatic carrier and evidence of its horizontal transmission. Virus Res 2002;90:133–141.
Sugauchi F, Mizokami M, Orito E, Ohno T, Kato H, Suzuki S, et al. A novel variant genotype C of hepatitis B virus identified in isolates from Australian Aborigines: complete genome sequence and phylogenetic relatedness. J Gen Virol 2001;82:883–892.
Ngui SL, O’Connell S, Eglin RP, Heptonstall J, Teo CG. 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.
Protzer-Knolle U, Naumann U, Bartenschlager R, Berg T, Hopf U, Meyer zum Buschenfelde KH, 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;27:254–263.
Rodriguez-Frias F, Buti M, Jardi R, Vargas V, Quer J, Cotrina M, et al. J. Genetic alterations in the S gene of hepatitis B virus in patients with acute hepatitis B, chronic hepatitis B and hepatitis B liver cirrhosis before and after liver transplantation. Liver 1999;19:177–182.
Ijaz S, Torre F, Tedder RS, Williams R, Naoumov NV. Novel immunoassay for the detection of hepatitis B surface “escape” mutants and its application in liver transplant recipients. J Med Virol 2001;63:210–216.
Kalinina T, Riu A, Fischer L, Will H, Sterneck M. 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.
Koyanagi T, Nakamuta M, Sakai H, Sugimoto R, Enjoji M, Koto K, et al. Analysis of HBs antigen negative variant of hepatitis B virus: unique substitutions, Glu129 to Asp and Gly145 to Ala in the surface antigen gene. Med Sci Monit 2000;6:1165–1169.
Ogata N, Zanetti AR, Yu M, Miller RH, Purcell RH. 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.
Shizuma T, Hasegawa K, Ishikawa K, Naritomi T, Iizuka A, Kanai N, et al. Molecular analysis of antigenicity and immunogenicity of a vaccine-induced escape mutant of hepatitis B virus. J Gastroenterol 2003;38:244–253.
Rehermann B, Ferrari C, Pasquinelli C, Chisari FV. The hepatitis B virus persists for decades after patients’ recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med 1996;2:1104–1108.
Grethe S, Monazahian M, Bohme I, Thomssen R. Characterization of unusual escape variants of hepatitis B virus isolated from a hepatitis B surface antigen-negative subject. J Virol 1998;72:7692–7696.
Westhoff TH, Jochimsen F, Schmittel A, Stoffler-Meilicke M, Schafer JH, Zidek W, et al. Fatal hepatitis B virus reactivation by an escape mutant following rituximab therapy. Blood 2003;102:1930.
Alexopoulou A, Baltayiannis G, Jammeh S, Waters J, Dourakis SP, Karayiannis P. Hepatitis B surface antigen variant with multiple mutations in the a determinant in an agammaglobulinemic patient. J Clin Microbiol 2004;42:2861–2865.
Alexopoulou A, Dourakis SP, Pandelidaki H, Archimandritis AJ, Karayiannis P. Detection of a hepatitis B surface antigen variant emerging in a patient with chronic lymphocytic leukaemia treated with fludarabine. J Med Virol 2006;78:1043–1046.
Awerkiew S, Daumer M, Reiser M, Wend UC, Pfister H, Kaiser R, et al. Reactivation of an occult hepatitis B virus escape mutant in an anti-HBs positive, anti-HBc negative lymphoma patient. J Clin Virol 2007;38:83–86.
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Kajiwara, E., Tanaka, Y., Ohashi, T. et al. Hepatitis B caused by a hepatitis B surface antigen escape mutant. J Gastroenterol 43, 243–247 (2008). https://doi.org/10.1007/s00535-007-2150-9
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DOI: https://doi.org/10.1007/s00535-007-2150-9