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.
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.
Schirren
Carl Albrecht
CA
Department of Medicine II, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, D-81377 Munich, Germany. schirren@med2.med.uni-muenchen.de
Zachoval
Reinhart
R
Gerlach
Joern Tilman
JT
Ulsenheimer
Axel
A
Gruener
Norbert Hubert
NH
Diepolder
Helmut Michael
HM
Baretton
Gustavo
G
Schraut
Winfried
W
Rau
Horst-Guenter
HG
Nitschko
Hans
H
Pape
Gerd Rudolf
GR
Jung
Maria-Christina
MC
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
D000998:Antiviral Agents