Z Gastroenterol 2006; 44 - A4_05
DOI: 10.1055/s-2006-931736

Differential expression of perforin in T-cells during interferon therapy of acute hepatitis C

N Aslan 1, J Wiegand 1, A Ciner 1, P Buggisch 2, MP Manns 1 H Wedemeyer 1, German Network of Competence on Viral Hepatitis („Hep-Net“)
  • 1Abt. Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
  • 2Universitätsklinikum Eppendorf, University of Hamburg, Germany

Introduction:

The role of different T cell subsets for the pathogenesis of acute hepatitis C and their contribution to viral clearance during interferon therapy are not well understood. Perforin expression is not restricted to CD8+T cells. We have preliminary evidence that perforin can be also found in CD4+T cells of patients with chronic viral hepatitis and that there is a correlation of perforin-positive CD4+T cells with disease activity. The effect of interferon therapy on perforin expression of T cells is unknown.

In this study we examined the effects of PEG-IFNa–2b therapy on perforin expression in different lymphoid cell subsets in acute HCV infection. Seven patients (3 male, 4 female; 34±13 years, 5 patients with HCV-genotype1 and 2 with genotype 3) were included. PBMC were collected frequently prior, during and after therapy and cryopreserved cells were used for analysis.

A sustained virological and biochemical response to therapy was observed in 4 cases, one patient experienced a relapse, one showed a breakthrough and one cleared HCV-RNA spontaneously without any therapy. Although the frequency of perforin+ CD4+T cells was lower than HIV-infected controls, we observed a strong association between perforin expression in CD4+T cells and ALT levels prior to and during therapy. Perforin positive CD4+T cells did not correlate with HCV-RNA titers. In contrast to CD4+Tcells, perforin expression of CD8+T cells and CD4/CD8-negative lymphoid cells did not correlate with any biochemical marker of disease activity. In sustained responder patients (5/7), slightly higher perforin expression was present before treatment, but declined during therapy.

These data suggest that (i) cytotoxic CD4+T cells contribute to disease activity in acute hepatitis C infection. (ii) Perforin expression in CD4+T cells is driven by inflammation rather than by HCV viremia. (iii) Interferon alpha treatment itself does not seem to cause direct changes in perforin expression of T cells in vivo.

Key words

CD4 - HCV - IFN - perforin