rtL180M mutation of hepatitis B virus is closely associated with frequent virological resistance to adefovir dipivoxil therapy
Article first published online: 20 JAN 2012
© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 27, Issue 2, pages 300–305, February 2012
How to Cite
Lee, Y.-S., Chung, Y.-H., Kim, J. A., Jin, Y. J., Park, W. H., Kim, S. E., Lee, D., Shim, J. H., Kim, K. M., Lim, Y. S., Lee, H. C., Lee, Y. S. and Suh, D. J. (2012), rtL180M mutation of hepatitis B virus is closely associated with frequent virological resistance to adefovir dipivoxil therapy. Journal of Gastroenterology and Hepatology, 27: 300–305. doi: 10.1111/j.1440-1746.2011.06853.x
- Issue published online: 20 JAN 2012
- Article first published online: 20 JAN 2012
- Accepted manuscript online: 20 JUL 2011 07:20AM EST
- Accepted for publication 8 June 2011.
- adefovir dipivoxil;
- hepatitis B virus;
- rtL180M mutation;
- virological resistance
Background and Aim: We intended to investigate the effects of pre-existing mutations at reverse transcriptase region of hepatitis B virus (HBV) on the occurrence of virological breakthrough (VB) to adefovir dipivoxil (ADV) in patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB).
Methods: Ninety-seven patients with LAM-resistant CHB were treated with ADV at a dose of 10 mg daily, and were followed for a median period of 13 months. Just before the initiation of ADV therapy, the whole length of reverse transcriptase region of serum HBV-DNA was sequenced using direct sequencing.
Results: All patients had genotype C HBV and mutations in the YMDD motif, specifically, YIDD (65%), YVDD (28%), or both (7%). The rtL180M and rtL80V/I mutations were identified in 68% and 69%, respectively. The cumulative probability of VB was 19% and 27% at 1 and 2 years, respectively. There was no difference in the occurrence of VB with regard to types of YMDD mutation or rtL80V/I. However, interestingly, patients carrying rtL180M experienced VB during ADV monotherapy more frequently than those not carrying rtL180M (2-year cumulative probability of VB: 37% vs 3% at 2 years, P < 0.01). On multivariate Cox proportional hazards analysis, rtL180M (hazard ratio [HR]: 8.62, 95% confidence interval: 1.08–69.09, P = 0.042) and decrease in HBV-DNA for 1 year of treatment (HR: 0.69, 95% CI: 0.51–0.95, P = 0.024) are independently associated with VB.
Conclusions: The rtL180M mutation of HBV, as well as a small decrease in HBV-DNA after 1 year of treatment might be closely associated with frequent occurrence of virological resistance to ADV in patients with LAM-resistant CHB.