Rescue therapy for lamivudine‐resistant chronic hepatitis B: Comparison between entecavir 1.0 mg monotherapy, adefovir monotherapy and adefovir add‐on lamivudine combination therapy

Abstract

There have been no reports comparing the therapeutic results of adefovir (ADV) and entecavir (ETV) rescue therapy for patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB). We aimed to compare the cumulative efficacy and resistance of ETV 1.0 mg monotherapy, ADV monotherapy and ADV add-on LAM combination therapy in LAM-refractory patients. One hundred and four patients were included in the following three treatment groups; group 1 (n = 24), LAM was switched to ETV (1.0 mg once a day); group 2 (n = 44), LAM was switched to ADV (10 mg once a day); and group 3 (n = 36), ADV was added to LAM (10 mg once a day). After 6 months of rescue treatment, alanine aminotransferase normalization was observed in 75.0%, 65.9% and 74.3% of patients receiving ETV monotherapy, ADV monotherapy and ADV add-on therapy, respectively. A significantly higher log(10)HBV-DNA drop at 6 months occurred in the ADV add-on group compared with the ETV group. The rate of HBV-DNA polymerase chain reaction undetectability (<300 copies/mL) 6 months after initiation of ETV monotherapy, ADV monotherapy and ADV add-on therapy was 33.3%, 27.3% and 68.6%, respectively (P = 0.003). The cumulative HBeAg seroconversion rate was significantly higher in ADV add-on/ADV monotherapy groups compared with the ETV monotherapy group (P = 0.022). Viral breakthrough and genotypic resistance were detected in six (25.0%) and six (13.6%) patients in the ETV and ADV monotherapy groups, whereas no cases of genotypic resistance were detected in ADV add-on group 24 months after initiation of antiviral treatment (P < 0.01). Adefovir add-on treatment in patients with LAM-resistant CHB suppresses HBV replication more effectively than ETV or ADV monotherapy. Additionally, no genotypic resistance was detected in the ADV add-on group.