Serum tumour necrosis factor-alpha and transforming growth factor-beta levels in chronic hepatitis C patients are immunomodulated by therapy.
Our aims were: (i) to characterize serum levels of tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) in non-cirrhotics with hepatitis C; (ii) to correlate levels of theses cytokines with degree of disease at baseline; (iii) to characterize the immunomodulatory effects of therapy with response and (iv) to compare profiles of cytokines in patients treated with pegylated-interferon alpha-2b monotherapy (PMT) vs its combination with ribavirin (PCT1-low dose ribavirin and PCT2-high dose ribavirin). We studied 56 patients that were part of two randomized, controlled, clinical trials. At baseline, high TNF-alpha levels paralleled the degree of inflammation as determined by histology. In PCT2, a significant reduction was seen in levels of TNF-alpha, TGF-beta and fibrosis scores 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. In conclusion, PCT2 is able to constantly reduce and sustain TNF-alpha levels, which is responsible for the sustained decline in liver inflammation as shown by the histological activity index and it is also able to reduce fibrosis as judged both by TGF-beta levels and fibrosis scores.
Neuman
Manuela G
MG
Division of Clinical Pharmacology, E-240, Sunnybrook and Women's College Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada. manuela@sten.sunnybrook.utoronto.ca
Benhamou
Jean-Pierre
JP
Bourliere
Marc
M
Ibrahim
Asma
A
Malkiewicz
Izabella
I
Asselah
Tarik
T
Martinot-Peignoux
Michelle
M
Shear
Neil H
NH
Katz
Gady G
GG
Akremi
Raoudha
R
Benali
Souad
S
Boyer
Nathalie
N
Lecomte
Laurence
L
Le Breton
Veronique
V
Le Guludec
Gaelle
G
Marcellin
Patrick
P
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000097:blood*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a