Liver immunolocalization and plasma levels of MMP-9 in non-alcoholic steatohepatitis (NASH) and hepatitis C infection

SummaryNon-alcoholic steatohepatitis (NASH) is a progressive fibrotic disease. Many issues related to the pathogenesis of this disease remain unresolved. Because of NASH association with the activation of liver fibrogenesis, we examined the plasma levels and liver immunolocalization of matrix metalloprotease-9 (MMP-9), a molecule involved in the remodelling processes of fibrogenesis. In addition, patients with chronic hepatitis C (HCV) were analyzed. Plasma concentrations of MMP-9 were determined by ELISA from peripheral blood and immunohistochemistry of the same protein was carried out in formalin-fixed and paraffin wax-embedded liver specimens. The mean value of circulating concentrations of MMP-9 in healthy controls was 39.7 ng/ml (SD: ±4.6). In NASH and HCV-infected patients, MMP-9 concentrations were higher: 69.0 ng/ml (SD: ±14.5) and 61.7 ng/ml (SD: ±11.0), respectively. In NASH livers, MMP-9 was mainly immunolocalized on neutrophils, whereas in HVC-infected livers it was mainly localized over biliary canaliculi, bile ducts and hepatocyte cytoplasm. The different MMP-9 immunolocalization patterns in the examined diseases suggest the presence of a different pathophysiological involvement of this protease in the fibrogenesis underlying these diseases.