Abstract
BackgroundDevelopment of the hepatitis B virus (HBV) rtA181T/sW172* mutant could occur during prolonged lamivudine (LAM) therapy, conferring cross resistance to adefovir. Recent studies demonstrated an increased oncogenic potential of this mutant in NIH3T3 cells. In this study, we aimed to investigate the clinical significance of this finding.MethodsSerum samples from 123 LAM-resistant chronic hepatitis B patients were submitted for virological assays. A highly sensitive amplification created restriction enzyme site (ACRES) method was devised to detect small amounts of the rtA181T mutant in the serum. Virological factors including HBV-DNA level, genotype, precore G1896A, BCP A1762T/G1764A, rtM204I/V, rtA181T and pre-S internal deletion mutations as well as clinical variables including subsequent use of rescue drugs were submitted for outcome analysis.ResultsBy use of the highly sensitive ACRES method, the rtA181T mutant was detectable in 10 of the 123 LAM-resistant patients. During the mean follow-up period of 26.2 ± 16.4 months (range 2 to 108 months), 3 of the 10 (30.0%) rtA181T-positive patients and 2 of the 113 (1.8%) rtA181T-negative patients developed hepatocellular carcinoma (HCC). Kaplan-Meier analysis indicated that the presence of rtA181T mutation (P < 0.001), age > 50 years (P = 0.001), and liver cirrhosis (P < 0.001) were significantly associated with subsequent occurrence of HCC. All 5 HCC patients belonged to the older age and cirrhosis groups.ConclusionsEmergence of the rtA181T/sW172* mutant in LAM-resistant patients increased the risk of HCC development in the subsequent courses of antiviral therapy.
Highlights
Introduction to chronic hepatitis B infectionAm JGastroenterol 2006, 101(Suppl 1):S1-6. 2
The risk increased to 21% in LAM-resistant patients who were switched to adefovir dipivoxial (ADV) monotherapy after 1.5 years of ADV therapy [2,3]
Tenofovir has recently been found to be effective in suppressing hepatitis B virus (HBV) replication with a low risk of drug resistance and several reports have shown that this drug is effective against various nucleotide analogues (NA) resistant or cross-resistant mutants [18,19]
Summary
Introduction to chronic hepatitis B infectionAm JGastroenterol 2006, 101(Suppl 1):S1-6. 2. Development of the hepatitis B virus (HBV) rtA181T/sW172* mutant could occur during prolonged lamivudine (LAM) therapy, conferring cross resistance to adefovir. Much progress has been made in antiviral therapy for chronic hepatitis B virus (HBV) infection [1,2,3]. The risk of developing ADV resistance was 2-3% and 28-29% by the second and fifth years of monotherapy in treatment naïve patients respectively [12,13,14]. The risk increased to 21% in LAM-resistant patients who were switched to ADV monotherapy after 1.5 years of ADV therapy [2,3]. The risk of developing telbivudine resistance was 2-3% and 21% after 1 and 2 years of therapy in treatment-naïve HBeAg-positive patients respectively. Tenofovir has recently been found to be effective in suppressing HBV replication with a low risk of drug resistance and several reports have shown that this drug is effective against various NA resistant or cross-resistant mutants [18,19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
