Effect of pegylated interferon alpha 2b plus ribavirin treatment on plasma transforming growth factor-beta1, metalloproteinase-1, and tissue metalloproteinase inhibitor-1 in patients with chronic hepatitis C.
OBJECTIVE
To evaluate the effect of antiviral treatment on plasma levels of transforming growth factor-beta1 (TGF-beta1), metalloproteinase 1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with chronic hepatitis C.


METHODS
TGF-beta1, MMP-1, and TIMP-1 plasma concentrations were measured by an enzyme immunoassay in 28 patients, during 48 wk of treatment with pegylated interferon-alpha 2b (PEG-IFN-alpha2b) plus ribavirin (RBV) and after 24 wk of follow-up. Patients were divided into two groups: responders (R) and non-responders (NR) related to achieved sustained virologic response. Normal values were evaluated in plasma samples of 13 healthy volunteers.


RESULTS
Baseline plasma concentrations of TGF-beta1 and TIMP-1 (30.9+/-3.7 and 1 506+/-61 ng/mL respectively) measured in all subjects significantly exceeded the normal values (TGF-beta1: 18.3+/-1.6 ng/mL and TIMP-1: 1 102+/-67 ng/mL). In contrast, pretreatment MMP-1 mean level (6.5+/-0.9 ng/mL) was significantly lower than normal values (11.9+/-0.9 ng/mL). Response to the treatment was observed in 12 patients (43%). TGF-beta1 mean concentration measured during the treatment phase decreased to the control level in both groups. However at wk 72, values of NR patients increased and became significantly higher than in R group. TIMP-1 concentrations in R group decreased during the treatment to the level similar to normal. In NR group, TIMP-1 remained significantly elevated during treatment and follow-up phase and significant difference between both groups was demonstrated at wk 48 and 72. MMP-1 levels were significantly decreased in both groups at baseline. Treatment caused rise of its concentration only in the R group, whereas values in NR group remained on the level similar to baseline. Statistically significant difference between groups was noted at wk 48 and 72.


CONCLUSIONS
These findings support the usefulness of TGF-beta1, TIMP-1, and MMP-1 in the management of chronic hepatitis C. Elevated TIMP-1 and low MMP-1 plasma concentrations during antiviral therapy may indicate medication failure.
Flisiak
Robert
R
Department of Infectious Diseases, Medical University of Bialystok, Bialystok, Poland. flisiakr@priv.onet.pl
Jaroszewicz
Jerzy
J
Lapinski
Tadeusz W
TW
Flisiak
Iwona
I
Prokopowiczi
Danuta
D
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004337:Drug Carriers / Q000627:therapeutic use; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood*; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D013223:Statistics as Topic; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1
D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D011092:Polyethylene Glycols; D012254:Ribavirin; D020781:Matrix Metalloproteinase 1; C417083:peginterferon alfa-2b