Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine
Article first published online: 6 NOV 2007
Alimentary Pharmacology & Therapeutics
Volume 27, Issue 3, pages 266–273, February 2008
How to Cite
MANOLAKOPOULOS, S., BETHANIS, S., KOUTSOUNAS, S., GOULIS, J., VLACHOGIANNAKOS, J., CHRISTIAS, E., SAVERIADIS, A., PAVLIDIS, C., TRIANTOS, C., CHRISTIDOU, A., PAPATHEODORIDIS, G., KARAMANOLIS, D. and TZOURMAKLIOTIS, D. (2008), Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine. Alimentary Pharmacology & Therapeutics, 27: 266–273. doi: 10.1111/j.1365-2036.2007.03567.x
- Issue published online: 6 NOV 2007
- Article first published online: 6 NOV 2007
- Publication data Submitted 2 August 2007First decision 3 September 2007 Resubmitted 1 October 2007 Accepted 30 October 2007
Vol. 27, Issue 6, 528–529, Article first published online: 20 FEB 2008
Background The efficacy of long-term adefovir dipivoxil monotherapy or combination of adefovir and lamivudine in hepatitis B e antigen (HBe-Ag)-negative lamivudine-resistant chronic hepatitis B (CHB) patients is still under investigation.
Aim To assess the safety and efficacy of the long-term adefovir treatment alone or in combination with lamivudine in HBe-Ag-negative CHB patients who had developed breakthrough because of lamivudine-resistant mutants.
Methods Fifty-nine patients received combination therapy, while 23 switched to adefovir alone after a 3-month course of combination therapy.
Results The median follow-up after adefovir’s onset was 31 (18–40) months. Baseline characteristics were similar between the two groups. At 12 and 24 months, 69% and 89% of patients receiving combination therapy and 73% and 82% of patients receiving adefovir monotherapy had serum HBV-DNA <104 copies/mL (P > 0.5). Normalization of alanine aminotransferase levels occurred in 81% and 79% of patients receiving combination vs. 61% and 53% receiving adefovir monotherapy at 12 and 24 months, respectively (P > 0.50). Virological breakthroughs because of adefovir-resistant mutants occurred in five patients under adefovir monotherapy and in none receiving combination therapy (P = 0.001). No one developed decompensated liver disease or hepatocellular carcinoma during follow-up. Re-introduction of lamivudine in adefovir-resistant patients achieved reduction in HBV-DNA and biochemical remission, but re-emergence of lamivudine mutants was observed in one patient after 7.5 months.
Conclusion In HBe-Ag-negative CHB patients with lamivudine resistance, adding adefovir to continuing lamivudine therapy maximizes anti-viral efficacy because of absence of viral resistance.