Chronic hepatitis B (CHB) patients with higher hepatitis B virus (HBV) load (higher viral load [HVL], HBV
DNA ≥1 × 107 copies/mL) require
antiviral therapy, but data for evaluating the long-term outcome of this
therapy with
antiviral agents remain limited. We comparatively evaluated the efficacy and the safety of
nucleoside analogues in 179 noncirrhotic CHB patients with HVL over 5 years. The
HBeAg-positive (n = 104) or
HBeAg-negative (n = 75) patients were treated consecutively with
telbivudine (LdT, n = 88) or
entecavir (ETV, n = 91) and evaluated for viral response, drug resistance and safety. HBV
DNA, viral serology, biochemistries, HBV mutation and off-
therapy relapse were determined. The cumulative rates of HBV
DNA negativity were 86.4% and 94.5% for LdT and ETV at year 5, respectively. The rates of early viral response (EVR, HBV
DNA <103 copies/mL at month 6) under LdT and ETV treatments were 58.0% and 34.1%, respectively (P < .05).
Hepatitis B e antigen (
HBeAg) and
Hepatitis B surface antigen (
HBsAg) loss-seroconversions were 47.7% and 18.2% on LdT and 16.5% and 2.2% on ETV (P < .01). Eighteen patients (age 28.2 ± 3.1) experienced
HBsAg loss-seroconversion, followed by 33 ± 4.6 month off-
therapy without a relapse. Viral mutations and serum
creatine kinase elevation were 9.1% and 8.0% on LdT, but only 1.1% and 0% on ETV. Both LdT and ETV suppressed HBV replication in HVL CHB patients within 5 years. LdT
therapy achieved a higher EVR,
HBeAg and
HBsAg seroconversion, especially in the younger patients, whereas ETV caused lower drug resistance and fewer adverse events. This finding might help to identify the optimal treatment for CHB patients with HVL.