Antiviral Therapy May Promote Hepatitis B Virus Genotype Changes

Hepatitis B virus (HBV) is known for its ability to mutate rapidly as it replicates, which enables it to develop resistance to antiviral treatment. As reported in the November 2008 Journal of Hepatology, a team of Spanish researchers assessed the frequency of mixed HBV genotypes in people with chronic hepatitis B, as well as genotype changes during natural disease evolution and as a result of antiviral therapy.

In a cross-sectional study, the investigators analyzed serum samples from 103 chronic hepatitis B patients. They also performed a longitudinal study of HBV genotypes in 22 patients, 17 of whom were receiving antiviral therapy with lamivudine (Epivir-HBV) and/or adefovir (Hepsera). HBV genotyping was done using the INNO-LiPA HBV assay.


• HBV genotypes observed in the cross-sectional study were as follows:

• A: 32% of cases;

• D: 42%;

• C: 2%;

• F: 2%;

• G: 7%, always combined with other genotypes.

• mixed genotypes: 22% (mainly A/D, followed by A/G).

• In the longitudinal study, genotype changes were observed in 9 patients, all of whom were on treatment.

• Genotype A strains were positively selected in 6 of these individuals, mainly as mixed A/D.

• In 6 patients, genotype A selection coincided with a decrease in HBV DNA levels.

Based on these findings, the study authors concluded, "A high frequency of mixed HBV genotypes was observed in our setting."

"Selection of genotype A strains during treatment is likely an indication that sensitivity to therapy differs between genotypes A and D," they continued. "The absence of changes in untreated patients suggests that HBV genotype is stable without external factors."

Hospital General Universitario Vall d'Hebrón, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.



R Jardi, F Rodriguez-Frias, M Schaper, and others. Analysis of hepatitis B genotype changes in chronic hepatitis B infection: Influence of antiviral therapy. Journal of Hepatology 49(5): 695-701. November 2008. (Abstract).