Not uncommon: HBV genotype G co-infections among healthy European HBV carriers with genotype A and E infection.

BACKGROUND & AIMS HBV genotype G (HBV/G) is mainly found in coinfections with other HBV genotypes and was identified as an independent risk factor for liver fibrosis. This study aimed to analyse the prevalence of HBV/G coinfections in healthy European HBV carriers and to characterize the crosstalk of HBV/G with other genotypes. METHODS 560 European HBV carriers were tested via HBV/G-specific PCR for HBV/G coinfections. Quasispecies distribution was analyzed via deep sequencing and the clinical phenotype was characterized regarding qHBsAg-/HBV-DNA levels and frequent mutations. Replicative capacity and expression of HBsAg/core was studied in hepatoma cells co-expressing HBV/G with either HBV/A, HBV/D or HBV/E using bicistronic vectors. RESULTS Although no HBV/G coinfection was found by routine genotyping PCR, HBV/G was detected by specific PCR in 4-8% of patients infected with either HBV/A or HBV/E but only infrequently in other genotypes. In contrast to HBV/E, HBV/G was found as the quasispecies major variant in coinfections with HBV/A. No differences in the clinical phenotype were observed for HBV/G coinfections. In vitro RNA and DNA levels were comparable among all genotypes but expression and release of HBsAg was reduced in co-expression of HBV/G with HBV/E. In co-expression with HBV/A and HBV/E expression of HBV/G-specific core was enhanced while core expression from the corresponding genotype was markedly diminished. CONCLUSIONS HBV/G coinfections are common in European inactive carriers with HBV/A and HBV/E infection, but sufficient detection depends strongly on the assay. HBV/G regulated core expression might play a critical role for survival of HBV/G in coinfections.