Is response to antiviral treatment influenced by hepatitis B virus genotype?

Recently released clinical practice guidelines and consensus conference statements point to the importane of hepatitis B virus (HBV) genotyping in therapeutic algorithms for the treatment of chronic hepatitis B. This information usually comes from post hoc analyses of clinical trials which were not designed to study associations with the HBV genotype. We have peformed a literature search through to April 2009 and have selected randomized clinical trials of currently approved anti-HBV drugs providing information on HBV genotypes and (i) baseline characteristics of study subjects, (ii) any response to antiviral therapy, (iii) interaction between HBV genotypes and the type of therapy. There were several intric features and weaknesses in majority of clinical trials conducted so far which make it difficult to reach firm conclusions about the role of HBV genotypes in response to antiviral therapy. Indeed most trials were necessarily multicenter in order to reach a sufficient statistical power, but pooling together patients of different ethnicities my have revealed false-positive associations between response to antiviral therapy and HBV genotype. Moreover, endpoint defintions, especially for the composite ones, varied substantially among studies, leading to lack of homogeneity. Finally, possible interactions between the type of therapy and the HBV genotype were only seldom analysed. The present review highlights several caveats regarding current indications proposed by the major clinical practice guidelines and consensus conference statements published thus far and emphasise the need for further long term studies in the field.