Genotype Mixtures of Hepatitis B Virus in Patients Treated with Interferon

Little is known about coinfection among several hepatitis B virus (HBV) genotypes, although previous reports of recombination and genotype shifts indicate that this should occur. In the present study, we designed a method to identify mixtures of genotype A and another genotype, regardless of whether one of them predominates. Using this method, signs of genotypic coinfection were found in 20 (67%) of 30 hepatitis B e antigen-positive patients treated with interferon (IFN). In 8 of these patients, coinfection or genotype shifts were detectable by direct sequencing or standard preS genotyping. In most of these cases, genotype changes were detected after a >2-log decrease or increase of the HBV DNA level. The presence of genotype mixtures did not significantly influence IFN response. Because quasi-species selection may occur at or shortly after transmission, patients might acquire HBV infection from subjects who appear to be infected with a different genotype. This should be considered when tracing the source of HBV infection.