A randomized controlled trial of sequential pegylated interferon-alpha and telbivudine or vice versa for 48 weeks in hepatitis B e antigen-negative chronic hepatitis B

Background: Short-term treatment for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B remains unsatisfactory. The aim of our study was to compare the efficacy and safety of two sequential regimens of pegylated interferon (PEG-IFN)-alpha and telbivudine (LdT). Methods: Adult patients with biopsy-proven HBeAg-negative chronic hepatitis B, elevated alanine aminotransferase (ALT) and serum HBV DNA >= 2,000 IU/ml were randomized 1: 1 at baseline to receive PEG-IFN 180 mu g/week for 24 weeks followed by LdT 600 mg/day for 24 weeks (PEG-IFN first), or vice versa (LdT first), plus 24-week follow-up; individuals with HCV, HDV or HIV coinfections and lamivudine resistance were excluded. Primary end points were serum HBV DNA<2,000 IU/ml and normal ALT at week 72. Results: A total of 30 patients (86% male, median age 48 years) were enrolled: mean +/- sd baseline serum HBV DNA was 5.56 +/- 1.4 log IU/ml and ALT was 2.9 +/- 2.5x upper limit of normal. At end of follow-up (week 72), HBV DNA<2,000 IU/ml was achieved in 13.3% of participants in the PEG-IFN first group versus 46.7% of those in the LdT first group (P=0.046). Mean +/- sd ALT levels were significantly lower in the LdT first group (1.3 +/- 0.9 versus 3.2 +/- 2.7x upper limit of normal; P=0.03). PEG-IFN dose was reduced in 2 (7%) patients and 1 (7%) patient dropped out due to myalgia. Conclusions: Sequential treatment with 24 weeks PEGIFN followed or preceded by 24 weeks of LdT is safe. Virological response rate at week 72 was significantly higher in patients treated with LdT followed by PEGIFN than vice versa. A sequential antiviral regimen of LdT followed by PEG-IFN, if confirmed in larger series, could improve response rates compared with standard PEG-IFN monotherapy.