Entecavir monotherapy for lamivudine-refractory chronic hepatitis B.

EVALUATION OF: Sherman M, Yurdaidin C, Simsek H et al. Entecavir therapy for lamivudine-refractory chronic hepatitis B: improved virologic, biochemical and serology outcomes through 96 weeks. Hepatology 48, 99-108 (2008). This article evaluates the efficacy, safety and resistance profile of entecavir treatment in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B lamivudine-refractory patients. A total of 286 patients were randomized and treated with entecavir 1 mg (n = 141) or continued lamivudine 100 mg (n = 145). At week 52, 77 entecavir-treated patients with a protocol-defined virologic response continued blinded therapy for up to 96 weeks. Cumulative proportions of all treated patients who achieved confirmed efficacy end points were also analyzed. It was shown that with 2 years of treatment, 30% of all entecavir-treated patients achieved HBV DNA of less than 300 copies/ml by PCR and 85% had alanine aminotransferase normalization (vs 1 and 29% of lamivudine-treated patients; p < 0.0001). HBeAg seroconversion was achieved by 17% of all entecavir-treated patients (24 out of 141) versus 6% of all lamivudine-treated patients (8 out of 1450; p < 0.0011) and was sustained in 11 patients (7.8%) 6 months after treatment discontinuation. However, entecavir treatment was associated with an increasing rate of drug resistance. Therefore, entecavir monotherapy does not appear to be the treatment of choice for lamivudine-refractory HBV patients and either a combination of potent antivirals with nonoverlapping resistance patterns or the use of newer nucleotides as monotherapy (e.g., tenofovir) could be helpful in the management of this difficult population.