[HBV gene variants and polymerse gene mutations in children with chronic hepatitis B in the course of the antiviral therapy].
THE AIM OF THE STUDY was to evaluate the occurrence of HBV genotypes and the emergence of polymerase gene mutations in children with chronic hepatitis B in the course of the lamivudine therapy.


METHODS
eighteen children (aged from 6 to 15 years, mean age 11,8 years, 10 boys and 8 girls) with chronic hepatitis B were included in the study. All patients were treated with 100 mg lamivudine tablets given daily orally for 12-16 months. All amino acid substitutions within HBV polymerase were detected by PCR amplification and direct sequencing HBV genotypes and polymerase gene mutations were determined by comparing the sequences in the overlapping PollS genes with published sequences, available in GenBank.


RESULTS
HBVgenotyping showed the presence of genotype A in 17 children and genotype H in one. No change of HBV genotype was noted in any of the studied patients as the sequencing of HBV DNA was repeated during the lamivudine therapy. The presence of lamivudine-resistance mutations involving the YMDD motif was detected in 5 patients. Four children had YVDD mutation, while in one child YIDD mutation was detected. YIDD mutation appeared to be the single one in the viral polymerase gene, while YVDD mutations in four patients were accompanied by other changes at amino acid sequence of the HBV polymerase: rtL180M, rtN124D and rtL164M.


CONCLUSIONS
1) Genotype A was predominant in the studied population of patients. 2) The risk of the emergence of drug-resistant HBV polymerase mutations is high and increases in the course of the lamivudine therapy. 3)Drug-resistant mutations in the YMDD motif are accompanied by other amino acid substitutions in the viral polymerase of unclear clinical significance.
Góra-Gebka
Magdalena
M
Katedra i Klinika Pediatrii Gastroenterologii i Onkologii Dzieciecej AM w Gdańsku. mgora@amg.gda.pl
Liberek
Anna
A
Charmuszko
Urszula
U
Sikorska-Wiśniewska
Grazyna
G
Szlagatys-Sidorkiewicz
Agnieszka
A
Korzon
Maria
M
Bielawski
Krzysztof
K
D000293:Adolescent; D000998:Antiviral Agents / Q000008:administration & dosage; D002648:Child; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000201:enzymology / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction
D000998:Antiviral Agents; D019259:Lamivudine; D004259:DNA-Directed DNA Polymerase