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

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.

Detection of circulating hepatitis B virus immune escape and polymerase mutants among HBV-positive patients attending Institut Pasteur de Bangui, Central African Republic

“…The study did not cover the entire CAR or Bangui populations, but was focused on individuals who were diagnosed at Institut Pasteur de Bangui from 2017 to 2019. This study detected three IEMs, sY100C, sA128V, and sM133T, similar to previous studies (Mello et al, 2011, Kwei et al, 2013, Cremer et al, 2018). Although data on IEMs in CAR are limited, the hypothesis of escape mutation among circulating HBV strains in the CAR was referred to previously in a study performed in 2013 (Komas et al, 2013).…”

“…As suggested by Mello et al (Mello et al, 2011), other mutations like K122R and F134I detected in the ‘a’ determinant support the idea of IEMs associated with strains harboring the sY100C as discussed in the present study. The mutation sA128 V was confirmed by geno2pheno HBV, and this IEM was associated with vaccine escape in a recent study conducted by Cremer et al (Cremer et al, 2018), who linked it with HBsAg test failure. Many studies (Protzer-Knolle et al, 1998, Beckebaum et al, 2003, Cheung et al, 2010) have demonstrated that M133T itself is frequently associated with occult HBV infection and is also often associated with some mutations in the ‘a’ determinant such as G130N, F134L, D144A, D144G, G145A, G145K, and G145R or failed hepatitis B immune globulin (HBIG) prophylaxis.…”

Detection of Q129H Immune Escape Mutation in Apparently Healthy Hepatitis B Virus Carriers in Southwestern Nigeria

“…The divergence within the a-determinant of HBV genotype E from all other genotypes is posing a challenge to the effectiveness of the current hepatitis B vaccine to efficiently protect against HBV infection as the vaccine has the HBsAg genotype A2. A similar challenge faces the vaccine in Central and South America and some Asian countries, such as Japan and Korea, where HBV genotypes F and C are predominant, respectively [ 44 , 45 , 46 ]. To further question the role of the current HBV vaccine in escape mutation, Hsu et al [ 47 ] found that vaccinated subjects had a tendency towards higher mutation rates in a determinant of HBsAg than unvaccinated subjects.…”

Immune-Escape Hepatitis B Virus Mutations Associated with Viral Reactivation upon Immunosuppression

“…All of them influence the antigenicity of HBsAg and are sometimes referred to as “immune-escape” mutations. It is important to note that these escape mutations can arise from host factors alone, without selection caused by vaccination or anti-HBV immunoglobulin therapy [54,55].…”