Entecavir shows limited efficacy in HBeAg-positive hepatitis B patients with a partial virologic response to adefovir therapy☆

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.

Abbreviations: HBV, hepatitis B virus, LAM, lamivudine, ADV, adefovir dipivoxil, TDF, tenofovir disoproxil fumarate, ETV, entecavir

Keywords: Hepatitis B treatment, Entecavir, Adefovir, Suboptimal response, Antiviral drug resistance