Published online Nov 21, 2005. doi: 10.3748/wjg.v11.i43.6833
Revised: May 8, 2005
Accepted: May 12, 2005
Published online: November 21, 2005
AIM: To evaluate the effect of antiviral treatment on plasma levels of transforming growth factor-β1 (TGF-β1), metalloproteinase 1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with chronic hepatitis C.
METHODS: TGF-β1, 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-α2b) 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-β1 and TIMP-1 (30.9±3.7 and 1 506±61 ng/mL respectively) measured in all subjects significantly exceeded the normal values (TGF-β1: 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-β1 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.
CONCLUSION: These findings support the usefulness of TGF-β1, 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.