Acute hepatitis B virus infection by genotype F despite successful vaccination in an immune-competent German patient

Abstract number: 1733_988

Amini-Bavil-Olyaee S., Heim A., Luedde T., Manns M., Trautwein C., Tacke F.

Background and Aims: Hepatitis B Virus (HBV) infection is a leading cause of chronic hepatitis and liver cirrhosis worldwide, and efficient protection can usually be achieved by vaccination that is based on recombinant HBsAg protein from HBV genotype A and D. We report the case of a fully immune-competent German patient that acquired a symptomatic acute HBV infection during adulthood despite a complete and formally successful vaccination, which had resulted in anti-HBs titers considered protective.

Case presentation and Methods: A 32 year old, fully immune-competent German male was referred with classical symptoms of acute hepatitis, including jaundice, fatigue and generalised skin rash. Initial aminotransferase activities were AST 525 U/L (normal <50) and ALT 567 U/L (normal <30), HBsAg and HBeAg were positive, and the copy number of HBV DNA was 26,700 copies/mL by real-time PCR (Roche). The HBV infection was most likely acquired in Spain during a business trip as a mining engineer, and resolved without specific therapy within 6 months. The patient had completed a full three-doses-course of vaccination about 10 months prior to infection. HBV DNA was extracted, amplified, sequenced and subjected for sequence and phylogenetic analyses.

Results: At the time of acute HBV infection, `protective' anti-HBs antibody titers of 50 IU/L (AxSYM AUSAB, Abbott Diagnostics) or 82 IU/L (Enzygnost, Dade Behring) were determined using two independent test systems. Phylogenetic analysis revealed that the isolated HBV strain classified into genotype F, sub-genotype F1 and cluster Ib with bootstrap values of 99, 98 and 85%, respectively. Interestingly, this genotype is extremely rare in Europe. The HBsAg sequence showed no apparent aberrations in the immunodominant `a' determinant domain of the envelope gene. However, sequence comparisons revealed that all reported genotype F isolates display marked differences from the other genotypes in this domain which serves as an epitope for humoral immune responses.

Conclusions: Current vaccines may not confer full protection against rare genotypes, even if no specific mutations in the `a' determinant epitope are present. It should be considered for future HBV vaccines to comprise immunodominant proteins from all HBV genotypes to cover genetic variability flaw among different HBV genotypes.