Matrix metalloproteinases 2 and 9 are markers of inflammation but not of the degree of fibrosis in chronic hepatitis C

Abstract

Background: The degree of liver fibrosis and inflammation is important in patients with chronic hepatitis C (CHC) in terms of therapy as well as prognosis. To obviate the need of liver biopsy, serum markers such as procollagen I, III and hyaluronic acid have been proposed but were found to be inaccurate. Controversy still exists regarding the role of matrix metalloproteinases (MMPs) as valid markers of liver fibrosis.

Aim: To assess liver and serum MMP-2 and -9 as markers of fibrosis and inflammation in patients with CHC.

Methods: Thirty-five CHC patients and 8 non-hepatitis C patients with normal liver enzymes underwent liver biopsy. Activities of inflammation and fibrosis stage were determined by the Desmet score on a scale of 0-4. Serum and liver tissue MMP-2 and -9 activities were measured by zymography using substrate impregnated gels.

Results: Patient and control groups were similar in terms of age (50.8 +/- 15.1 vs. 50.6 +/- 15.2) and male/female ratio (18/17 vs. 4/4). In serum, MMP-9 activity was increased in patients compared to controls (308 +/- 110 vs. 163.5 +/- 35 , p < 0.05). In liver tissue, MMP-9 was also higher in patients than in controls (21 +/- 4.5 vs. 17.1 +/- 5.1, p < 0.05), whereas MMP-2 did not differ between patients and controls. Serum MMP-9 values correlated with liver histologic inflammatory grade (290.4 +/- 83 in grade 2 vs. 562.1 +/- 128 in grade 3, p < 0.05) but not with fibrosis stage. The highest rising in serum MMP-9 levels was observed between grade 2 to grade 3 and was superior to the rising in serum transaminase levels, indicating its advantage in assessing the progression of disease activity. No correlation between liver MMP activities and liver fibrosis or inflammation was observed.

Conclusion: Serum MMPs, in particular MMP-9, can serve as markers of disease activity rather than fibrosis stage in chronic HCV patients.