2) Division of Clinical Pharmacology, Sunnybrook and Women's College Health Sciences Centre, and Department of Pharmacology, University of Toronto, Toronto, Canada. 2) Service d' Hepatologie et Pathologie, INSERM U481and Hopital Beaujon, Clichy. 3) Hopital Saint Joseph, Marseille, France. 4) Department of Biostatistic, School of Medicine and Pharmacy, Bucharest, Romania

Abstract

Aims. (i) To characterize serum levels of pro/anti-inflammatory cytokines in non-cirrhotics with hepatitis C; (ii) to correlate levels of theses cytokines with degree of disease at baseline; and (iii) to characterize the immuno-mmodulatory effects of therapy with response. Methods. We studied 103 patients that were part of randomized, controlled, clinical trials. Serum cytokines were measured using enzyme-linked immunosorbent assay. Results. Using standard therapy in the presence and absence of ribavirin, the sustained responders had lower baseline tumor necrosis alpha (TNF-?) levels as compared to relapsed responders and non-responders. In patients receiving pegylated therapy, the degree of inflammation as determined by histology was paralleled by high TNF-? levels at baseline. In pegylated combination therapy with high dose ribavirin, lower levels of TNF-?, transforming growth factor beta (TGF-?) and fibrosis scores were seen when comparing baseline with follow up. In sustained responders, regardless of therapy, the histological activity scores were lower at follow up as compared to baseline. Conclusions. Pegylated combination therapy reduces and sustains TNF-?? levels and liver inflammation as shown by the histological activity index. In addition, it is able to reduce fibrosis as judged both by TGF-?? levels and fibrosis scores as compared to standard therapy.

Key words

Chronic hepatitis C - cytokines - standard/pegylated-interferon-alpha - ribavirin/ Cluster analysis in fuzzy rule base reduction