Role of cytokines in the assessment of the severity of chronic hepatitis C and the prediction of response to therapy.
OBJECTIVE
(i) To characterize serum levels of pro/anti-inflammatory cytokines in non-cirrhotics with hepatitis C; (ii) to correlate levels of these cytokines with degree of disease at baseline; and (iii) to characterize the immuno-modulatory 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-alpha) 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-alpha levels at baseline. In pegylated combination therapy with high dose ribavirin, lower levels of TNF-alpha, transforming growth factor beta (TGF-beta) 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-alpha levels and liver inflammation as shown by the histological activity index. In addition, it is able to reduce fibrosis as judged both by TGF-beta levels and fibrosis scores as compared to standard therapy.
Neuman
Manuela G
MG
Division of Clinical Pharmacology E-240, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada.
Benhamou
Jean-Pierre
JP
Ibrahim
Asma
A
Malkiewicz
Izabella
I
Spircu
Tiberius
T
Martinot-Peignoux
Michelle
M
Shear
Neil H
NH
Katz
Gady G
GG
Akremi
Raoudha
R
Bourliere
Marc
M
Marcellin
Patrick
P
D000970:Antineoplastic Agents / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005544:Forecasting; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000517:prevention & control; D011237:Predictive Value of Tests; D012254:Ribavirin / Q000627:therapeutic use*; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D014409:Tumor Necrosis Factor-alpha; D012254:Ribavirin