We read the article published by Alagozlu et al. (2013) with interest. The authors found that 100% of chronic HBV patients who underwent antiviral therapy using either lamivudine/adefovir alone or in combination, contained either silent (24.4%) or missense (75.6%) mutations in their YMDD motif of HBV polymerase proteins. A variety of unusual silent mutations were found in the former group. Authors did not present the details for treatment regimen for patients group. Therefore, the mutation

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... les in the text cannot be assigned to the type of drug-used. However, some comments deserve to mention. Interestingly, authors found a population of transitions/transversion nucleotide substitutions that might have some impacts on HBV combination therapy. Our unpublished data on Iranian genotype D patients (the same main genotype circulating in Turkey) confirms such hypothesis. We investigated the mutational profile for 3 similar groups as Alagozlu et al's study (Mahabadi et al., 2013) . In Lamivudine-only group, we found F221Y/S and L229G which are related to adefovir (ADV) resistancy. W153Q, I169T, A200V and S202G which are related to Lamivudine-resistancy were found in ADV-only group. Finally, highest frequency of substitutions for residues L180M (43.7%) and M204I/V (68.7%) were found for Lamivudine/ADV combination group than all other groups. L217R and L229M/W were found in combination group. All of these patients showed partial resistance to these drugs, thus, they switched to other new anti-HBV nucleoside analogues regimen. Among 100 treatmentnaïve patients (control group), we found a variety of above mono/combination mutations in an average of 1-8%. Similarly, in another national-based retrospective study, 2.4 to 17.3% of treatment naïve patients contained a cocktail of either mono-or combination related mutations; ii) Therefore the silent mutations found in Alagozlu study, highlights significant concerns about the potential role of such mutations on the evolution of HBV in patients under therapy. Finding of 58.5% wild type genotype instead of mutations in YMDD in Alagozlu's study in some patients is not surprising, as direct sequencing usually fails to detect about 25% of exact mutational patterns of the samples studied. Thus, the existence of other mutational profile in a viral pool quasi-species with wild type dominancy cannot be ruled out.