The primary objective of treatment of chronic hepatitis B is to produce sustained suppression of HBV replication.

Nucleoside-naive patients who completed 24 or 52 weeks of treatment in the Japanese entecavir (Baraclude) studies ETV-047 and ETV-053 enrolled in an open-label rollover study, ETV-060). The efficacy, safety, and resistance profile of long-term treatment with 0.5 mg once-daily entecavir was evaluated in these patients.

In total, 32 of 34 ETV-047 participants (94%) and all 34 ETV-053 participants (100%) treated with 0.5 mg entecavir enrolled in ETV-060 without a treatment gap. HBV DNA by PCR, histological improvement, ALT, and HBV serology were assessed in ETV-060 participants with evaluable samples through 3 years.

Resistance analysis was also performed by sequence analysis of the HBV polymerase region in samples obtained from all patients with virological breakthrough (1 log10 increase in HBV DNA from nadir) or with detectable HBV DNA (400 copies/mL).

Results were reported at the 43rd annual meeting of the European Association for the Study of the Liver (EASL) last month in Milan.

Results

• In ETV-060, 58 of 66 patients (88%) were treated for a minimum of 96 weeks (total 120-148 weeks).

• Continued treatment with entecavir resulted in an increase in the proportion of patients achieving HBV DNA < 400 copies/mL from study entry in ETV-060 through week 96:

• from 44% (14/32) to 80% (20/25) in patients from ETV-047;

• from 68% (23/34) to 85% (28/33) in patients from ETV-053.

• Histological improvement was observed in 100% of patients (19/19) with repeated biopsies.

• Additional seroconversion occurred in 19% of patients (9/48).

• ALT normalization increased from 89% (55/62) at ETV-060 entry to 96% (53/55) at week 96.

• 66 patients were monitored for resistance and HBV rtDNA was successfully amplified and sequenced in 10 patients with detectable HBV DNA, of whom 1 patient had evidence of entecavir resistance substitutions.

• The 3-year cumulative probability of entecavir resistance in these patients was 1.7% (1/58 at year 3).

• 3 patients discontinued therapy due to adverse events (2) or insufficient efficacy (1).

In conclusion, the investigators wrote, "Long-term treatment of nucleoside-naive Japanese patients with entecavir 0.5 mg was well tolerated and demonstrated increasing proportions of patients achieving undetectable HBV DNA and histologic improvement."

In addition, they noted, "entecavir continues to show a high barrier to resistance with a cumulative 3-year resistance rate of 1.7%."

Saitama Medical University, Saitama, Japan; Kagawa Prefectural Central Hospital, Kagawa, Japan; Graduate School of Medicine, Chiba University, Chiba, Japan; Okayama Saiseikai General Hospital, Okayama, Japan; Osaka University Graduate School of Medicine, Osaka, Japan; Division of Liver Disease, Akashi Municipal Hospital Hyogo, Japan; Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan; Sapporo Kosei General Hospital, Hokkaido, Japan; Graduate School of Medicine, University of Tokyo, Tokyo, Japan. Bristol-Myers Squibb Research and Development, Tokyo, Japan;

5/06/08

Reference
S Mochida, K Takaguchi, O Yokosuka, and others. Long term efficacy, safety and resistance analyses of entecavir (entecavir treatment in Japanese nucleoside-naive patients with chronic hepatitis B (CHB). 43rd Annual Meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.