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 5 log10 copies/mL after 12 months of adefovir therapy and thereafter were treated with entecavir 1 mg daily. Results: During a median follow-up of 15 months (range: 8-23 months) one of six lamivudine-naïve and none of the eight lamivudine-experienced patients achieved undetectable HBV DNA (<373 copies/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 2 mg daily in two patients, resulting in further viral load decline for both of them. Conclusions: Entecavir monotherapy dosed at 1 mg 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.
|Keywords||Adefovir, Antiviral drug resistance, Entecavir, Hepatitis B treatment, Hepatitis B virus, Suboptimal response, adefovir, adult, aged, alanine aminotransferase, alanine aminotransferase blood level, antiviral resistance, antiviral therapy, article, blood sampling, clinical article, controlled study, drug dose increase, drug efficacy, drug response, drug substitution, drug treatment failure, drug withdrawal, entecavir, female, follow up, gene mutation, genotype, hepatitis B, hepatitis B(e) antigen, human, human tissue, lamivudine, male, monotherapy, priority journal, treatment duration, virus DNA, virus load|
|Persistent URL||dx.doi.org/10.1016/j.jhep.2008.10.033, hdl.handle.net/1765/18282|
|Journal||Journal of Hepatology|
Reijnders, J.G.P, Pas, S.D, Schutten, M, de Man, R.A, & Janssen, H.L.A. (2009). Entecavir shows limited efficacy in HBeAg-positive hepatitis B patients with a partial virologic response to adefovir therapy. Journal of Hepatology, 50(4), 674–683. doi:10.1016/j.jhep.2008.10.033