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Evolution of hepatitisB virus mutation during nucleoside/tide analogues long-term therapy in chronic hepatitisB patients

Abstract number: P1149

Arrese E., Basaras M., Blanco S., Ruiz P., Cisterna R.

Objective: The aim of the present study was to evaluate the therapy with nucleos(t)ide analogues (adefovir dipivoxil (ADV), lamivudine (LAM), entecavir (ETV)) in chronic hepatitis B virus (HBV) infected patients with frequent measurements of DNA levels, to characterize HBV genotypes, and to determine the emergence of nucleos(t)ide analogues mutants before and during the two years of therapy by direct sequencing.

Patients and Methods: A total of twenty patients with chronic HBV infection were treated with nucleos(t)ide analogues for at least two years. We studied nucleos(t)ide analogue-naïve patients as well as patients previously treated with another nucleos(t)ide analogue. A virologic breakthrough was defined as an increase in serum HBV DNA level and resistance to therapy was defined as the emergence of resistance mutations by direct sequencing of the polymerase gene, which was looked for in all HBV DNA positive serum samples.

Results: Viral genotype was determined showing the presence of genotype D (55%) in eleven patients, genotype A (40%) in eight patients and genotype C (5%) in one patient. In the viral response to long-term treatment, three patients developed LAM resistance mutations (rtM204V/I+rtL180M; M204I; M204I+rtQ215S), one patient developed ETV resistance (rtM204V+rtL180M+rtT184A+rtS202G), one patient developed ADV resistance mutations (rtA181V+rtQ215S) and another patient developed ADV+LAM resistant mutations (rtL180M+rtA181V+rtN236T). In another two patients, the viral load did not respond sufficiently to therapy but they did no developed nucleotide changes in the polymerase gene associated with viral resistance. On the other hand, in twelve patients the viral load was undetectable after two years of treatment.

Conclusions:

1Frequent assessment of quantitative serum HBV DNA remains the best approach to early detection of resistance.

2Direct sequence analysis is an essential tool to detect mutations and to optimize therapeutic management of HBV chronic infection in clinical practice in order to choose the appropriate nucleos(t)ide analogues.

Session Details

Date: 10/04/2010
Time: 00:00-00:00
Session name: Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Vienna, Austria, 10 - 13 April 2010
Presentation type:
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