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. 2018 Oct;90(10):1576-1585.
doi: 10.1002/jmv.25232. Epub 2018 Jun 7.

Genetic variation of hepatitis B surface antigen among acute and chronic hepatitis B virus infections in The Netherlands

Jeroen Cremer  1 , Sanne H I Hofstraat  1 , Francoise van Heiningen  1 , Irene K Veldhuijzen  1 , Birgit H B van Benthem  1 , Kimberley S M Benschop  1
Affiliations

Genetic variation of hepatitis B surface antigen among acute and chronic hepatitis B virus infections in The Netherlands

Jeroen Cremer et al. J Med Virol. 2018 Oct.

Abstract

Genetic variation within hepatitis B surface antigen (HBsAg), in particular within the major hydrophobic region (MHR), is related to immune/vaccine and test failures and can have a significant impact on the vaccination and diagnosis of acute infection. This study shows, for the first time, variation among acute cases and compares the amino acid variation within the HBsAg between acute and chronic infections. We analyzed the virus isolated from 1231 acute and 585 chronic cases reported to an anonymized public health surveillance database between 2004 and 2014 in The Netherlands. HBsAg analysis revealed the circulation of 6 genotypes (Gt); GtA was the dominant genotype followed by GtD among both acute (68.2% and 17.4%, respectively) and chronic (34.9% and 34.2%, respectively) cases. Variation was the highest among chronic strains compared to that among acute strains. Both acute and chronic GtD showed the highest variation compared to that of other genotypes (P < .01). Substitutions within the MHR were found in 8.5% of the acute strains and 18.6% of the chronic strains. Specific MHR substitutions described to have an impact on vaccine/immune escape and/or HBsAg test failure were found among 4.1% of the acute strains and 7.0% of the chronic strains. In conclusion, we show a high variation of HBsAg among acute and chronic hepatitis B virus-infected cases in The Netherlands, in particular among those infected with GtD, and compare, for the first time, variation in frequencies between acute and chronic cases. Additional studies on the impact of these variations on vaccination and test failure need to be conducted, as well as whether HBsAg false-negative variants have been missed.

Keywords: amino acid variation; hepatitis B surface antigen; hepatitis B virus; major hydrophobic region; test failure; vaccination.

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Figures

Figure 1
Figure 1
Maximum parsimony tree of the HBsAg of HBV strains isolated from 1232 Dutch acute HBV–infected cases characterized between 2004 and 2014. The cases are color‐coded by infection status and sex. Gt, genotype; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus
Figure 2
Figure 2
Variation frequency within the HBsAg ranging from a no substitution to 1 to 10 substitutions among acute and chronic strains. The data set for acute cases is a representative set of acute HBV in The Netherlands. The data set for chronic cases only represents those with risk behavior from various risk groups (<2010) and in most cases from MSM (>2010). The HBsAg amino acid sequence variation of the 6 genotypes was compared to the respective reference type 7. HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; MSM, men who have sex with men
Figure 3
Figure 3
Frequency and distribution of amino acid substitutions within the HBsAg (amino acid residues 1 to 203) of genotypes A to F. Acute strains are shown in blue bars and chronic strains are in red bars. Positions associated with vaccine/immune escape and/or test result are boxed. Gt, genotype; HBsAg, hepatitis B surface antigen
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