OBJECTIVETo evaluate the efficacy and safety of entecavir (ETV) in treating lamivudine refractory chronic hepatitis B (CHB) patients.

METHODSThis was part of a multicenter, double-blinded, randomized (4:1) and placebo-controlled trial comparing the safety and efficacy of ETV (1.0 mg once q.d.) for 12 weeks in lamivudine refractory CHB patients. All patients were treated with ETV (1.0 mg q.d.) for 168 weeks. During the treatment period, HBV DNA levels were regularly measured by quantitative PCR. Liver function tests, HBV serology and safety assessments were also conducted.

RESULTSThe mean of HBV DNA log10 decreased from 9.14 to 6.27 at week 2, decreased to 6.28 at week 4, to 5.46 at week 8, to 5.10 at week 12, to 4.49 at week 24, to 4.41 at week 48, to 3.91 at week 96, to 4.05 at week 144, and decreased to 4.21 at week 168. The proportion of HBV DNA more than 10(5) copies/ml gradually dropped from 100% at baseline to 46.43% at week 12 and to 17.86% at week 96. HBV DNA less than 10(3) copies/ml raised from 0 at baseline to 7.14% at week 8, to 10.71% at week 12, to 46.43% at week 96, and raised to 57.14% at week 168. The proportion with HBeAg seroconversion was 10.07% at the end of the study. The mean of ALT became normal at week 12 and remained normal throughout week 168. There was one patient who had a severe adverse event during the trial.

CONCLUSIONETV can effectively inhibit the replication of HBV DNA and normalize the levels of ALT in lamivudine refractory CHB patients, and from our study we think the use of ETV is safe.