Lamivudine and adefovir resistance in children and young adults with chronic hepatitis B.
OBJECTIVE
Long-term lamivudine (LAM) and adefovir (ADV) treatment has been found to induce the emergence of drug-resistant hepatitis B virus (HBV) in a significant number of patients with chronic hepatitis B (CHB) infection. The aim of our study was to evaluate the LAM and ADV mutations detected in our patient group.


METHODS
Twenty-four patients diagnosed with CHB were enrolled in this study. The patient group consisted of those who had received 6 months of treatment with interferon-alpha and who did not response to this therapy. Patients were evaluated based on virologic and serologic response to therapy, and were classified as responders or non-responders. The treatment of non-responders continued with LAM (3mg/kg/d, maximum 100mg/d). Due to a lack of response to treatment, ADV (10mg/g) was added to the treatment regimen of eight young adult patients. The mutations associated with HBV drug resistance were investigated using reverse hybridization methods and PCR.


RESULTS
The mutation studies indicated that 14 (58.4%) of the patients had resistance. Three patients developed ADV-associated mutations (A181T), one after 18 months of ADV; the other two had undergone 18 and 36 months of LAM therapy without ADV exposure. Although the average LAM treatment period of the patients with LAM resistance was longer than for those in whom no resistance was detected, no statistically significant difference was found.


CONCLUSIONS
HBV treatment with nucleoside analogues results in the development of mutant strains, leading to drug resistance. Therefore genotypic resistance testing is important in planning and monitoring HBV treatment.
Akman
Sezin Asik
SA
Department of Pediatric Gastroenterology, The Ministry of Health Tepecik Training and Research Hospital, Izmir, Turkey. sezin.akman@gmail.com
Kose
Sukran
S
Halicioglu
Oya
O
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D055815:Young Adult
D000998:Antiviral Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C053001:adefovir; D000225:Adenine