title: A randomized controlled trial of sequential pegylated interferon-α and telbivudine or vice versa for 48 weeks in hepatitis B e antigen-negative chronic hepatitis B.
abstract: 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)-α 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 μg/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 ± 2.5× 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 ± 2.7× 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 PEG-IFN 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 PEG-IFN 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.
authors.affiliation: Hepatology Unit, Tor Vergata University, Rome, Italy. paola.piccolo@uniroma2.it
authors.forename: Paola
authors.initials: P
authors.lastname: Piccolo
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lenci
authors.forename: Daniele
authors.initials: D
authors.lastname: di Paolo
authors.forename: Luigi
authors.initials: L
authors.lastname: Demelia
authors.forename: Orazio
authors.initials: O
authors.lastname: Sorbello
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Nosotti
authors.forename: Mario
authors.initials: M
authors.lastname: Angelico
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007558:Italy; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077712:Telbivudine; D013936:Thymidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000077712:Telbivudine; D011092:Polyethylene Glycols; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a; D013936:Thymidine