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HBV quasispecies heterogeneity influences virologic response with genetic barrier nucleoside analogs

April's issue of the Journal of Viral Hepatitis investigates the dynamics of hepatitis B virus quasispecies heterogeneity, and virologic response in patients receiving low-to-moderate genetic barrier nucleoside analogs.

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Dr Peveling-Oberhag and colleagues characterized the early dynamics of hepatitis B virus quasispecies evolution during the first weeks of antiviral therapy with low-to-moderate genetic barrier antiviral drugs and associated these data with antiviral response patterns.

The team evaluated 15 chronic hepatitis B patients who received lamivudine or telbivudine for at least 52 weeks.

The research team reported that hepatitis B virus DNA was extracted from serum, and a 910-bp fragment covering domains A–F of the reverse transcriptase region was amplified, cloned and sequenced.

Parameters of quasispecies heterogeneity, genetic diversity and complexity were calculated and were correlated with complete virologic response, defined as undetectable hepatitis B virus DNA at week 52.

The research team found that 9 patients achieved complete virologic response during the observational period.

While baseline hepatitis B virus DNA levels and hepatitis B e antigen status were associated with virologic response, baseline quasispecies complexity and diversity of responders showed no significant difference to those of nonresponders.

The number of synonymous substitutions per synonymous site dropped in responders at week 4
Journal of Viral Hepatitis

The team of researchers noted that at week 4, quasispecies complexity of nonresponders was significantly higher compared with that of responders on the nucleotide level, and the aa level.

The number of synonymous substitutions per synonymous site dropped significantly in responders at week 4, while there was no difference in nonresponders.

Dr Peveling-Oberhag's team commented, "The hepatitis B virus quasispecies complexity at the early stage of antiviral therapy with the low-to-moderate genetic barrier nucleoside analogs lamivudine or telbivudine was associated with subsequent virologic response."

"Further studies are needed to confirm hepatitis B virus quasispecies evolution as additional predictive marker for beneficial treatment outcome."

J Viral Hep 2013: 20(4): 234-239
26 March 2013

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