title: Therapeutic vaccination in chronic hepatitis B.
abstract: OBJECTIVE
  The aim was to test the efficacy of a pre-S2-containing vaccine (Genhevac-B) in chronic hepatitis B (CHB). Twenty-five naive patients (22 male, three female; median age 35; range: 6-69 years) with CHB were recruited. The inclusion criteria were: hepatitis B e antigen (HBeAg) positive or HBV-DNA detectable with liquid hybridization; alanine aminotransferase (ALT) is at least 1.5-fold the upper normal limit and histological evidence of chronic hepatitis.
  
  
  METHODS
  In the first period, all patients received monthly injections of 20, 40 and 60 microg of the vaccine. One month after the last injection, patients who still had HBV-DNA were divided into two randomly assigned groups. While the patients in the first group and the patients who lost HBV-DNA in the first period continued to receive monthly injections of 20 microg vaccine for a further 6 months, the patients in the second group received 9 MU interferon alpha-2b (Roferon-A), three times per week using the same method as for the first group. Patients were followed up after 12 months without treatment. Response was defined as the loss of HBV-DNA and normalization of ALT.
  
  
  RESULTS
  Six of the 25 patients lost HBV-DNA after 3 months. Nine of the remainder were randomly placed in the first group (vaccine-only) and 10 were placed in the second group (vaccine + interferon). End-of-treatment response was achieved, overall, 8/15 from the vaccine group and 6/10 from the combination. One patient from each group relapsed during the follow up. Overall, the sustained response (SR) rate was 46% (7/15) in the vaccine group, and 50% (5/10) in the combination group. Histological improvement was achieved in 6/7 SR with vaccine-only and all five with combination treatment, while 1/8 of failures of vaccine and 2/5 of failures of combination improved.
  
  
  CONCLUSIONS
  It was concluded that Genhevac-B decreases serum HBV-DNA levels in the majority of patients with CHB and sustained clearance was achieved in some patients. Combination of interferon-alpha with Genhevac-B is effective for the vaccine failures and may increase sustained response compared to interferon-alpha alone. However, the mechanism of action is yet to be explained.
authors.affiliation: Department of Internal Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Turkey. haksen@escortnet.com
authors.forename: Hakan
authors.initials: H
authors.lastname: Senturk
authors.forename: Fehmi
authors.initials: F
authors.lastname: Tabak
authors.forename: Meral
authors.initials: M
authors.lastname: Akdogan
authors.forename: Levent
authors.initials: L
authors.lastname: Erdem
authors.forename: Ali
authors.initials: A
authors.lastname: Mert
authors.forename: Resat
authors.initials: R
authors.lastname: Ozaras
authors.forename: Ersan
authors.initials: E
authors.lastname: Sander
authors.forename: Gulsen
authors.initials: G
authors.lastname: Ozbay
authors.forename: Selim
authors.initials: S
authors.lastname: Badur
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers; D002648:Child; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000187:drug effects; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D006513:Hepatitis B e Antigens / Q000097:blood / Q000187:drug effects; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000410:Alanine Transaminase