Entecavir shows limited efficacy in HBeAg-positive hepatitis B patients with a partial virologic response to adefovir therapy☆
Received 11 June 2008; received in revised form 8 October 2008; accepted 22 October 2008. published online 29 December 2008.
Background/Aims
We investigated the efficacy of entecavir in lamivudine-experienced and -naïve patients with persistently high HBV DNA during adefovir treatment.
Methods
Fourteen chronic hepatitis B patients (57% lamivudine-experienced) with a viral load above 5log10copies/mL after 12months of adefovir therapy and thereafter were treated with entecavir 1mg daily.
Results
During a median follow-up of 15months (range: 8–23months) one of six lamivudine–naïve and none of the eight lamivudine-experienced patients achieved undetectable HBV DNA (<373copies/mL). HBeAg loss occurred in none of the subjects. Two lamivudine-experienced patients demonstrated the rtM204I mutation; no other entecavir-resistant substitutions were detected (rtI169, rtT184, rtS202, and rtM250). Two of three patients with genotypic adefovir resistance at baseline demonstrated a rapid virologic response to entecavir, but undetectable HBV DNA was not achieved. To attain a better antiviral response the dosage of entecavir was increased to 2mg daily in two patients, resulting in further viral load decline for both of them.
Conclusions
Entecavir monotherapy dosed at 1mg resulted in a slow reduction of viral load in both lamivudine-experienced and -naïve patients with persistently high HBV DNA during adefovir therapy. Increasing the dosage of entecavir led to further HBV DNA decline.
1Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, ’s Gravendijkwal 230, Room Ha 204, 3015 CE Rotterdam, The Netherlands
2Department of Virology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
☆ H.L.A. Janssen received grants from and is consultant for: Bristol Myers Squibb, Gilead, Novartis, Roche and Schering-Plough. R.A. de Man received an unrestricted research grant from Biotest, clinical trial support from Bristol Myers Squibb and Gilead, and is a member of the Data safety monitoring board of Novartis. The other authors have nothing to declare.
ABSTRACT