Altered pattern of circulating matrix metalloproteinases -2,- 9 and tissue inhibitor of metalloproteinase-2 in patients with HCV-related chronic hepatitis. Relationship to histological features

Abstract

Aim: The aim of this paper was to assess circulating levels of metalloprotease2 (MMP2), metalloprotease9 (MMP9) and tissue inhibitor of metalloprotease2 (TIMP2) in patients with HCV-related chronic hepatitis to verify whether there was a relationship between these molecules and biochemical and histological features.

Methods: Forty-nine neodiagnosed and untreated patients affected by chronic C hepatitis and twenty healthy control subjects were investigated. In overall study series, circulating levels of MMP2, MMP9 and TIMP2 were assessed by ELISA commercial kit (R&D Systems). Patients with chronic hepatitis undergone to liver biopsy and histological features were examined according to Histological Activity Index (HAI).

Results: Mean values of MMP2 (1989+/-207 ng/mL. vs 1112+/-120 ng/mL), MMP9 (62.44+/-11.9 ng/mL vs 39.67+/-4.6 ng/mL) and TIMP2 (48.3+/-8.1 ng/mL vs 15.16+/-4.1 ng/mL) were significantly higher (P<0.001) in patients than in controls. Among investigated molecules, only MMP2 was independently related to inflammation and fibrosis according to grading (P=0.036) and staging (P=0.032) score. Moreover, MMP2 but not MMP9 and TIMP2 was related to AST (P=0.015), ALT (P=0.049) and AST/platelet ratio index (P=0.001). No relationship (P>0.05) was found between MMP2 and MMP9 or TIMP2.

Conclusions: Our study confirms an altered pattern of metalloproteases and their tissue inhibitors in subjects with chronic C hepatitis and such alterations can contribute to development of liver fibrosis. In addition MMP2 is related to inflammation and fibrosis as assessed by liver biopsy and laboratory features. The serial detection of MMP2 could help to monitor evolution of disease and to predict onset of cirrhosis.