title: Entecavir and interferon-α sequential therapy in Japanese patients with hepatitis B e antigen-positive chronic hepatitis B.
abstract: BACKGROUND
  The outcomes of sequential therapy with lamivudine followed by interferon have been unsatisfactory in Japanese patients with hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B. However, the efficacy of sequential therapy with entecavir and interferon remains unclear.
  
  
  METHODS
  Twenty-four HBeAg-positive patients (23 men and 1 woman; mean age 39 ± 7 years) received entecavir 0.5 mg alone for 36-52 weeks, followed by entecavir plus interferon-α for 4 weeks, and lastly by interferon-α alone for 20 weeks. Twenty-three patients had genotype C infection, and one had genotype A infection.
  
  
  RESULTS
  No entecavir-resistant mutant variants emerged in any patient. Hepatitis flare occurred in three patients during interferon-α treatment after the withdrawal of entecavir, but none had hepatic decompensation. Serum hepatitis B surface antigen levels did not change during or after therapy. Serum hepatitis B core-related antigen levels were significantly decreased at the start (P < 0.0001) and at the end of interferon-α treatment (P < 0.0001), but returned to baseline levels after treatment. Twenty-four weeks after the completion of the sequential therapy, a sustained biochemical, virological, and serological response was achieved in 5 (21 %) patients. The proportion of patients in whom HBeAg was lost during entecavir treatment was significantly higher among those with a sustained response than among those with no response (P = 0.015).
  
  
  CONCLUSIONS
  The rate of response to sequential therapy with entecavir and interferon-α in Japanese patients with HBeAg-positive chronic hepatitis B was not higher than the rate in previous studies of lamivudine followed by interferon.
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Enomoto
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamori
authors.forename: Sawako
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Susumu
authors.initials: S
authors.lastname: Shiomi
authors.forename: Soo Ryang
authors.initials: SR
authors.lastname: Kim
authors.forename: Hirayuki
authors.initials: H
authors.lastname: Enomoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Saito
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Imanishi
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; C413685:entecavir; D006147:Guanine