Serum levels of matrix metalloproteinase-9 [MMP-9] and caspase-3 activity in chronic hepatitis C patients

ABSTRACT

During Hepatitis C virus infections, liver fibrosis results as a consequence of a progressive accumulation of extracellular matrix [ECM] proteins. While, matrix metalloproteinase-9 [MMP-9] has major actions in remodeling of ECM components, caspase-3 plays a key role in the execution of apoptosis implicated in HCV pathogenesis. The assessment of liver disease severity as well as monitoring of patients with chronic liver disease over time remains a major challenge nowadays. Thus, an urgent need to develop noninvasive reliable tests to monitor hepatic disease activity, especially serum biomarkers emerges. This study was conducted to evaluate serum levels of MMP-9 and caspase-3 in patients with chronic hepatitis C and their potential use as markers of hepatic impairment. Forty chronic HCV patients together with 20 healthy controls were enrolled in the present work. HCV viral load was evaluated by Real-time PCR. In addition, caspase-3 serum levels were measured using Instant ELISA and MMP-9 serum levels were measured by ELISA. Besides, serum aminotransferases' activities were measured by automated analyzer. Caspase-3 activity and MMP-9 levels were markedly elevated in the HCV patients' sera compared to controls [56.40 +/- 22.52 vs. 5.20 +/- 6.65 ng/ml; 190.29 +/- 144.16 v. 39.10 +/- 17.68 ng/ml, p<0.001, respectively]. Patients with AST/ALT ratio>1 demonstrated higher MMP-9 serum levels than those with ratio <1[p<0.001]. The same was observed for caspase-3; however, it did not reach statistical significance. A significant correlation was observed between these markers and AST as well as AST/ALT ratio. However, no correlation was observed with the viral load. MMP-9 and caspase-3 might be involved in HCV-associated liver injury. Measurement of MMP-9 and caspase-3 activities could be reliable markers for liver damage, which may open up new diagnostic and therapeutic strategies aimed at manipulating the early inflammation as well as the late fibrotic changes in HCV infection