The major neutralizing epitope, the “a” determinant of the hepatitis B virus (HBV) genotype E surface antigen (HBsAg) is most divergent from that of genotype A, which is used for preparing monoclonal antibodies used in commercially available HBV reagents. To evaluate the performance of the latest generation of HBsAg detection assays with respect to genotype E HBsAg. Three commercial assays were evaluated using sera from 200 Nigerian patients compared to the preS/S sequence of DNA positive samples. Out of 200 samples, 61 and 103 gave concordant positive and negative results between the three HBsAg assays. Of 36 samples with discordant results, 35 were confirmed negative by neutralisation. One of the three assays showed significantly high rate of false positives (29 of 35). DNA positive samples with no detectable HBsAg or reduced HBsAg detection signals (<75% of mean signal obtained with HBsAg positive samples) revealed several mutations (V14A, F46S, N48T, L49R, I49T, D51G, A53V, P54L, Q82P, F83C, L127P, A184V, T189I, S204N, V224A), mostly outside the a-determinant. Several of these mutations are found as wild type nucleotides normally in genotype A and only exceptionally in genotype E. All three assays showed comparable sensitivities for genotype E HBsAg detection (98.4–100%) but differed considerably in specificity (84–99%). Failure to detect HBsAg antigen and differences in signal intensity were mainly associated with mutations in the preS/S gene outside the “a” determinant.
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Alhababi F, Sallman TA, Tong CYW (2003) The significance of anti-HBc only in the clinical virology laboratory. J Clin Virol 27:162–169
Arauz-Ruiz P, Norder H, Visona KA, Magnius LO (1997) Genotype F prevails in HBV infected patients of Hispanic origin in Central America and may carry the precore stop mutant. J Med Virol 51:305–312
Bartholomeusz A, Schaefer S (2004) Hepatitis B virus genotypes: comparison of genotyping methods. Rev Med Virol 14:3–16
Echevarria JM, Leon P, Domingo CJ, Lopez LA, Echevarria JE, Contreras G, Fuertes A (1991) Characterization of HBV 2-like infections in Spain. J Med Virol 33:240–247
Echevarria JM, Leon P, Pozo F (2004) Hepatitis B virus surface antigen reactivity in the absence of antibodies to core antigen: an atypical serological pattern having diverse significance. Enferm Infecc Microbiol Clin 22:6–12
Echevarria JM, Avellon A, Magnius LO (2005) Molecular epidemiologhy of hepatitis B virus in Spain: identification of viral genotypes and prediction of antigenic subtypes by limited sequencing. J Med Virol 76:176–184
Günther S (2006) Genetic variation in HBV infection: genotypes and mutants. J Clin Virol 36:S3–S11
Huy TT, Ishikawa K, Ampofo W, Izumi T, Nakajima A, Ansah J, Tetteh JO, Nii-Trebi N, Aidoo S, Ofori-Adjei D, Sata T, Ushijima H, Abe K (2006) Characteristics of hepatitis B virus in Ghana: full length genome sequences indicate the endemicity of genotype E in West Africa. J Med Virol 78:178–184
Jardi R, Rodriguez F, Buti M, Costa X, Cotrina M, Valdes A, Galimany R, Esteban R, Guardia J (2001) Quantitative detection of hepatitis B virus DNA in serum by a new rapid real-time fluorescence PCR assay. J Viral Hepatitis 8:465–471
Kumar S, Tamura K, Nei M (2004) MEGA3: integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 5:150–163
Laperche S, Guitton C, Smilovici W, Courouce AM (2001) Blood donors infected with the hepatitis B virus but persistently lacking antibodies to the hepatitis B core antigen. Vox Sang 80:90–94
Levicnic-Stezinar S (2004) Hepatitis B surface antigen escape mutant in a first time blood donor potentially missed by a routine screening assay. Clin Lab 50:49–51
Mizuochi T, Okada Y, Umemori K, Mizusawa S, Yamaguchi K (2006). Evaluation of 10 commercial diagnostic kits for in vitro expressed hepatitis B virus (HBV) surface antigens encoded by HBV of genotypes A to H. J Virol Methods 136:254–256
Mulders MN, Venard M, Njayou M et al (2004) Low genetic diversity despite hyperendemicity of hepatitis B virus genotype E throughout West Africa. J Infect Dis 190:400–408
Ni YH, Hsu HY, Chang MH, Chen DS, Lee CY (1993) Absence or delayed appearance of hepatitis B core antibody in chronic hepatitis B surface antigen carrier children. J Hepatol 17:150–154
Norder H, Couroucé AM, Coursaget P, Echevarria JM, Lee SD, Mushahwar IK, Robertson BH, Locarnini S, Magnius O (2004) Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology 47:289–309
Odemuyiwa SO, Mulders MN, Oyedele OI, Ola SO, Odaibo GN, Olaleye DO, Muller CP (2001) Phylogenetic analysis of new hepatitis B virus isolates from Nigeria supports endemicity of genotype E in West Africa. J Med Virol 65:463–469
Olinger CM, Venard V, Njayou M, Oyefolu AO, Maiga I, Kemp AJ, Omilabu SA, le Faou A, Muller CP (2006) Phylogenetic analysis of the precore/core gene of hepatitis B virus genotypes E and A in West Africa: new subtypes, mixed infections and recombinations. J Gen Virol 87:1163–1173
Stuyver L, De Gendt S, Van Geyt C, Zoulim F, Fried M, Schinazi RF, Rossau R (2000) A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness. J Gen Virol 81:67–74
Thompson JD, Higgins DG, Gibson TJ (1994) Improved sensitivity of profile searches through the use of sequence weights and gap excision. Comput Appl Biosci 10:19
Valliammai T, Echevarria JM, Leon P, Tusets C, Harrison TJ (1995) Amplification and sequence analysis of the precore and core region of the HBV genome from sera of Spanish patients with HBV2-like infections. J Med Virol 46:375–379
Weber B (2005) Recent developments in the diagnosis and monitoring of HBV infection and role of the genetic variability of the S gene. Expert Rev Mol Diagn 5:75–91
Weber B, Dengler T, Berger A, Doerr HW, Rabenau H (2003) Evaluation of two new automated assays for hepatitis B virus surface antigen (HBsAg) detection: IMMULITE HBsAg and IMMULITE 2000 HBsAg. J Clin Microbiol 41:135–143
Weber B, Van der Taelem-Brule N, Berger A, Simon F, Geudin M, Ritter J (2006) Evaluation of a new automated assay for hepatitis B surface antigen (HBsAg) detection VIDAS HBsAg Ultra. J Virol Methods 135:109–117
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Olinger, C.M., Weber, B., Otegbayo, J.A. et al. Hepatitis B virus genotype E surface antigen detection with different immunoassays and diagnostic impact of mutations in the preS/S gene. Med Microbiol Immunol 196, 247–252 (2007). https://doi.org/10.1007/s00430-007-0050-5
- Genotype E
- Nucleic acid amplification test
- PreS/S gene