Dynamics of changes in the genome of hepatitis B virus for chronic HBsAg-carrier after Lamivudine treatment. Abstracts from the 50th European Society of Human Genetics Conferenceстатья
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Аннотация:Background: targeted therapy is the main goal of personalized medicine. High-throughput molecular genetic studies are particularly important in antiviral therapy and oncology to overcome drug resistance, to save time, and to predict the effectiveness of medical treatment. The aims of study: analysis of the dynamic effect of Lamivudine to HBV isolate with escape-mutation Gly145Arg under treatment of chronic HBsAg-carrier.
Methods: serum samples in time 2004-2007 were studied for patient 53 y/o with a combination of chronic hepatitis B and chronic Hodgkin's disease. Initial HBV isolate got Gly145Arg mutation, affecting changes in serological properties of the HBV samples. Medical treatment by Lamivudine since 2006 was started. High-throughput sequencing was performed by Ion Torrent PGM (2150x-2700x coverages). Informed consent was obtained from patient according local ethical approval.
Results: serological markers in the time series of sample were stable the entire period of observation (+/+/+/+/- profile for HBsAg/HBeAg/anti-HBe IgG/anti-HB с IgM+IgG/anti-HBsAg, respectively; HCV and HDV markers were negative). HBV isolate samples from 2004 and 2005 were identical. After Lamivudine therapy was started the HBV genome was mutated. HBV isolate acquired the resistance to Lamivudine by Y(M/V)DD, as well as codon of escape-mutation Gly145Arg got the second mutation resulting heterogeneity Gly145(Arg/Lys). The other important feature was the appearance of heterogeneous Gly10Lys mutation. Sequencing of HBV isolates from 2006 and 2007 proved their identity. Conclusion: in chronic HBsAg-carrier with Gly145Arg mutation in HBsAg region Lamivudine treatment resulting to the emergence of a drug-resistance mutation. This case illustrate importance of HBV isolate features for personalized therapy.