Entecavir is a potent and selective guanosine analogue with significant activity against Hepatitis B virus.
Dr Ting-Tsung Chang and colleagues conducted a phase 3, double-blind trial.
The investigators randomly assigned 715 patients with Hepatitis B e antigen-positive chronic Hepatitis B to 2 treatment groups for 52 weeks.
In a second study, the researchers randomly assigned 648 patients with Hepatitis B e antigen-negative chronic Hepatitis B who had not previously been treated with a nucleoside analogue.
In study 1, Group 1 included 314 patients receiving 0.5 mg of entecavir once daily.
There were another 314 patients in Group 2 receiving 100 mg of lamivudine once daily.
The patients had not previously received a nucleoside analogue.
| 72% with entecavir had histologic improvements after 48 weeks vs 62% with lamivudine|
The primary efficacy end point was histologic improvement at week 48.
Histological improvements were defined as a decrease by at least 2 points in the Knodell necroinflammatory score, without worsening of fibrosis.
The investigators' secondary end points included a reduction in the serum Hepatitis B DNA level, and Hepatitis B e antigen loss.
Other end points included seroconversion, and normalization of the alanine aminotransferase level.
The investigators found histologic improvement after 48 weeks in 72% of patients in Group 1, and 62% in Group 2.
The investigative team noted that more patients in Group 1 than in Group 2 had undetectable serum Hepatitis B DNA levels.
This was established by a polymerase-chain-reaction assay, and normalization of alanine aminotransferase levels.
The mean reduction in serum Hepatitis B DNA from baseline to week 48 was greater with entecavir than with lamivudine.
The team observed that Hepatitis B e antigen seroconversion occurred in 21% of entecavir-treated patients and 18% of those treated with lamivudine.
No viral resistance to entecavir was detected.
The investigators noted that safety was similar in the 2 groups.
Dr Chang's team concluded, “Among patients with Hepatitis B e antigen-positive chronic Hepatitis B, the rates of histologic, virologic, and biochemical improvement are significantly higher with entecavir than with lamivudine.”
“The safety profile of the 2 agents is similar, and there is no evidence of viral resistance to entecavir.”
"In the second study, among patients with Hepatitis B e antigen-negative chronic Hepatitis B who had not previously been treated with a nucleoside analogue, the rates of histologic improvement, virologic response, and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine."
"The safety profile of the 2 agents was similar, and there was no evidence of viral resistance to entecavir."