The oral
deoxyguanosine nucleoside analogue
entecavir (Baraclude®) has potent activity against hepatitis B virus (HBV) and a high genetic barrier to resistance. This article reviews the clinical efficacy and tolerability of
entecavir in the treatment of
chronic hepatitis B in patients with decompensated
liver disease, as well as summarizing its pharmacological properties.
Entecavir 1 mg/day was more effective than
adefovir dipivoxil 10 mg/day in the treatment of patients with
chronic hepatitis B and decompensated
liver disease, according to the results of a randomized, open-label, multicentre trial. Patients were either nucleos(t)ide naive or
lamivudine experienced. The reduction from baseline in HBV
DNA levels at week 24 (primary endpoint) was significantly greater with
entecavir than with
adefovir dipivoxil. The proportion of patients with HBV
DNA levels of <300 copies/mL was also significantly greater with
entecavir than with
adefovir dipivoxil at weeks 24, 48 and 96, as was the proportion of patients with ALT normalization.
Entecavir 0.5 or 1 mg/day,
tenofovir disoproxil fumarate 300 mg/day and a fixed-dose combination of
emtricitabine/
tenofovir disoproxil fumarate 200 mg/300 mg per day were effective in the treatment of
chronic hepatitis B in patients with decompensated
liver disease, according to the 48-week analysis of a randomized, double-blind, multicentre trial, primarily designed to examine tolerability endpoints. In this trial, over one-third of patients had received previous
therapy with
lamivudine for ≥6 months. The efficacy of
entecavir in treatment-naive patients with HBV-related decompensated
cirrhosis did not significantly differ from that seen in patients with
chronic hepatitis B or compensated
cirrhosis (compensated group), according to the results of a prospective, nonrandomized study. After 6 or 12 months of
entecavir treatment, there were no significant differences between the decompensated and compensated groups in virological, biochemical or serological endpoints. In patients with decompensated
cirrhosis, significant improvements from baseline in liver function were seen after 12 months of
entecavir therapy. Oral
entecavir was generally well tolerated in patients with
chronic hepatitis B and decompensated
liver disease, with most of the reported treatment-emergent adverse events consistent with decompensated
liver disease. In the trial primarily designed to examine tolerability endpoints, there was no significant difference between patients receiving
entecavir and those receiving
tenofovir disoproxil fumarate with or without
emtricitabine in terms of the proportion of patients experiencing tolerability failure or the proportion of patients with confirmed increases in serum
creatinine levels of ≥0.5 mg/dL above baseline or confirmed serum
phosphorus levels of <2.0 mg/dL at week 48 (co-primary endpoints). It has been suggested that the risk of
lactic acidosis associated with oral nucleos(t)ide analogue
therapy is increased in patients with highly impaired liver function. However, only one case of
lactic acidosis was reported among
entecavir recipients across two clinical trials in patients with
chronic hepatitis B and decompensated
liver disease. Moreover, small studies found that the risk of
lactic acidosis was not increased in patients with
chronic hepatitis B and decompensated
liver disease who received
entecavir, compared with patients with non-HBV decompensated
liver disease. In conclusion,
entecavir is a valuable agent for the first-line treatment of
chronic hepatitis B in patients with decompensated
liver disease.