Lamivudine-resistant chronic hepatitis B: An observational study on adefovir in monotherapy or in combination with lamivudine

Background/Aims: In lamivudine-resistant patients with chronic hepatitis B (CHB), we compared efficacy, predictive response factors and changes in viral mutants in two antiviral approaches with adefovir. Methods: A prospective cohort study on therapy with adefovir alone (29 patients) or combined with ongoing lamivudine (23 patients) was performed. Results: A virological response was achieved in 55% of patients treated with adefovir and in 83% of those treated with the combination (p > 0.05). This response was directly related to the basal viral load (p < 0.0001) and obtained in 10 patients with basal HBV-DNA < 17,200 IU/ml using both strategies. In patients with a higher basal viral load, the virological response was more frequent when treated with the combination (p < 0.05). Mutation at locus rt181 predicted HBV-DNA persistence during therapy. A virological rebound was observed in 18% of non-responders while on adefovir monotherapy. Conclusions: To achieve a complete virological response and reduce the risk of adefovir-resistant mutants in lamivudine-resistant patients, rescue therapy is preferable at early evidence of genotypic resistance. However, in subjects with a significant viral load, combination therapy is more effective. The presence of the rt181 mutation is associated with incomplete response. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.