title: Antiviral treatment of recurrent hepatitis C virus (HCV) infection after liver transplantation: association of a strong, multispecific, and long-lasting CD4+ T cell response with HCV-elimination.
abstract: OBJECTIVE
  Patients with recurrent hepatitis C virus (HCV)-infection after liver transplantation (OLTx) could develop an early, multispecific, preferentially intrahepatic CD4+ T cell response. We asked now whether there is a correlation between the HCV-specific CD4+ T cell response and treatment outcome in patients who receive interferon (IFN)-alpha/ribavirin.
  
  
  METHODS
  Liver- and blood-derived T cell lines of 20 patients were studied in parallel before, under, at the end and after antiviral treatment. Virus-specific IFN-gamma production at a single cell level to HCV-proteins (core, non-structural protein (NS)3/4, NS5) was determined by enzyme-linked immunospot assay.
  
  
  RESULTS
  In 6/7 non-responders a weak HCV-specific CD4+ T cell response was detectable. All six sustained responders developed a strong, at NS3/4 and NS5 directed and long-lasting CD4+ T cell response which was mainly detected in peripheral blood mononuclear cells. This reaction was significantly stronger: (1) in the responders than in the non-responders; and (2) within the responders at the end of treatment than before (P<0.03). Seven transient-responders showed a weak and/or transient HCV-specific CD4+ T cell response.
  
  
  CONCLUSIONS
  In patients with recurrent HCV-infection after OLTx, who receive antiviral treatment, a strong, at NS3/4 and NS5 directed and long-lasting CD4+ T cell response is associated with HCV-elimination whereas no or a weak/transient response is associated with treatment failure.
authors.affiliation: Department of Medicine II, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, D-81377 Munich, Germany. schirren@med2.med.uni-muenchen.de
authors.forename: Carl Albrecht
authors.initials: CA
authors.lastname: Schirren
authors.forename: Reinhart
authors.initials: R
authors.lastname: Zachoval
authors.forename: Joern Tilman
authors.initials: JT
authors.lastname: Gerlach
authors.forename: Axel
authors.initials: A
authors.lastname: Ulsenheimer
authors.forename: Norbert Hubert
authors.initials: NH
authors.lastname: Gruener
authors.forename: Helmut Michael
authors.initials: HM
authors.lastname: Diepolder
authors.forename: Gustavo
authors.initials: G
authors.lastname: Baretton
authors.forename: Winfried
authors.initials: W
authors.lastname: Schraut
authors.forename: Horst-Guenter
authors.initials: HG
authors.lastname: Rau
authors.forename: Hans
authors.initials: H
authors.lastname: Nitschko
authors.forename: Gerd Rudolf
authors.initials: GR
authors.lastname: Pape
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Jung
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents