The goal of chronic hepatitis B (CHB) treatment is complete and permanent eradication of
hepatitis B virus (HBV) from patient's body, which is best represented by serum HBsAg loss
accompanied by undetectable serum HBV DNA level.
While the most recently approved nucleos(t)ide analogues (NA) have marked antiviral potency
and can induce HBV DNA undetectability in the majority of patients through prolonged
treatment, NA need to be given long term, almost indefinitely, in most cases because they
suppress HBV DNA only during therapy. For example, even after HBeAg-loss by a potent NA,
suppression of serum HBV DNA to undetectable level is sustained only in about 23%-37% at 24
weeks off treatment. Thus, continuous therapy with NA until HBsAg clearance remains necessary
in a majority of cases.
The recent availability of commercial quantitative assays of serum hepatitis B surface
antigen (HBsAg) has enabled quantitative HBsAg to be used as a biomarker for prognosis and
treatment response in CHB. It has been suggested that HBsAg decline during lamivudine or
entecavir therapy is slower and less pronounced compared to interferon treatment, despite a
higher effect on HBV DNA suppression. Based on HBsAg kinetics, it has been estimated that the
predicted median time to HBsAg loss in patients treated with lamivudine or entecavir is more
than 30 years. Thus, treatment that can induce rapid decline of HBsAg would have clear
advantage in reducing the treatment duration required to achieve HBsAg-loss.
Interestingly, in a recent preliminary study, 24-weeks of treatment with telbivudine has
induced HBsAg decline as comparable to pegylated interferon treatment. Although there has
been no head-to-head trial comparing NAs in inducing HBsAg decline, previous studies
consistently suggested that the decline of HBsAg is greater during telbivudine treatment
compared with lamivudine or entecavir.
Thus, in this clinical trial, the investigators will investigate whether telbivudine is more
effective in inducing HBsAg decline compared with entecavir in HBeAg-positive CHB patients
who have achieved undetectable serum HBV DNA by preceding entecavir treatment.