title: The cellular immune responses induced in the follow-up of interferon-alpha treated patients with chronic hepatitis C may determine the therapy outcome.
abstract: OBJECTIVE
  To study whether the host's immune response determines viral clearance in chronic hepatitis C, virological markers and antigen-specific T cell reactions were analysed in 30 chronic HCV carriers followed up during interferon-alpha therapy, 11 untreated anti-HCV positive individuals and 10 healthy controls.
  
  
  METHODS
  Proliferative T helper cell responses to recombinant HCV core and non-structural antigens were monitored by 3H-thymidine uptake assay and compared to quantitative viraemia levels and HCV genotypes.
  
  
  RESULTS
  Of the 30 treated patients, six had sustained complete responses (20%), another six were transient therapy responders (20%) and 18 were non-responders (60%). Viral clearance was associated with the HCV genotype 3 and low pretreatment viral load. In a substantial proportion of complete and transient therapy responders, increased NS3-, helicase- and NS4-antigen-specific T cell responses were observed during interferon-alpha therapy. In non-responders and in the later clinical courses of transient therapy responders, core and NS5-specific T cell responses dominated. In addition, 11 untreated anti-HCV antibody positive individuals were studied. Two HCV-RNA negative patients who might have recovered from HCV infection showed strong persistent lymphoproliferative responses to NS3, helicase and NS4 antigens, whereas seven of the nine viraemic patients reacted with HCV core or NS5 antigens.
  
  
  CONCLUSIONS
  Interferon-alpha treatment enhances NS3-, helicase- and NS4-antigen-specific T helper cell responses in patients with viral clearance, whereas viral persistence was associated with increased T cell reactivities against core and NS5 antigens. Immunogenetical, immunological and virological factors that may influence differential T cell induction in chronic hepatitis C are discussed.
authors.affiliation: I. Department of Internal Medicine, Johannes-Gutenberg University, Mainz, Germany. loehr@.mail.zdv.uni-mainz.de
authors.forename: H F
authors.initials: HF
authors.lastname: Löhr
authors.forename: G
authors.initials: G
authors.lastname: Gerken
authors.forename: M
authors.initials: M
authors.lastname: Roth
authors.forename: S
authors.initials: S
authors.lastname: Weyer
authors.forename: J F
authors.initials: JF
authors.lastname: Schlaak
authors.forename: K H
authors.initials: KH
authors.lastname: Meyer zum Büschenfelde
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000276:immunology; D018936:Hepatitis C Antigens / Q000097:blood; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000628:therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014766:Viremia / Q000276:immunology / Q000628:therapy
chemical_list: D018936:Hepatitis C Antigens; D016898:Interferon-alpha; D012367:RNA, Viral