Adding-on versus switching-to adefovir therapy in... : Hepatology (original) (raw)
Original Articles
Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B
Rapti, Irene1; Dimou, Evangelini1,2; Mitsoula, Panayota2; Hadziyannis, Stephanos J.1,2*
1_Department of Medicine and Liver Unit, Henry Dunant Hospital, Athens, Greece_
2_Hepatitis Research Laboratory at Evgenidion Hospital, Athens University, Athens, Greece_
*Address reprint requests to: Department of Medicine & Liver Unit, Henry Dunant Hospital, 107 Messogion Avenue, 11526 Athens, Greece
Email:[email protected]
Received 11 August 2006; Accepted 15 November 2006
Published online in Wiley InterScience (www.interscience.wiley.com).
Potential conflict of interest: Nothing to report.
See Editorial on Page 266
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Abstract
We studied the long-term efficacy of adefovir dipivoxil (ADV) treatment in 42 HBeAg-negative patients with chronic hepatitis B (CHB) who had developed genotypical lamivudine (LAM) resistance with virological and clinical breakthroughs under long-term LAM treatment. Patients were allocated in 2 treatment groups. In the first (n = 14), LAM was switched to ADV monotherapy whereas in the second (n = 28) ADV was added to LAM. The two groups did not differ in patients' characteristics, all of them having HBV genotype D infection with the precore stop codon mutation. Within 12 months from start of ADV treatment, serum HBV DNA became nondetectable and ALT normalized in 71% and 90% of patients, respectively, with no difference between the 2 arms. Patients with baseline HBV DNA levels less than 107 copies/ml experienced a significantly earlier and more frequent decline in serum HBV DNA to nondetectable levels as compared with patients with greater than 107 HBV DNA copies/ml at baseline ( P = 0.0013) This response has hitherto been maintained (median treatment duration 40 months) in all patients with ADV added to LAM, whereas virological and biochemical breakthroughs due to development of ADV signature resistance mutations occurred in 3 of 14 patients (21%) on ADV monotherapy 15 to 18 months from start of treatment ( P = 0.0174).
Conclusion:
Adding ADV to LAM in HBeAg-negative CHB patients with LAM resistance effectively suppresses HBV replication in most of them and induces biochemical remission that can be maintained in all of them at least for 3 years without any evidence of development of resistance to ADV.
Abbreviations: ADV, adefovir dipivoxil; CHB, chronic hepatitis B; HBeAg, hepatitis B e antigen; LAM, lamivudine.
Copyright © 2007 American Association for the Study of Liver Diseases.