Clinical usefulness of serum matrix metalloproteinase-2 concentration in patients with chronic viral liver disease

Background/Aims: The production of matrix metalloproteinase (MMP)-2 was reported to be increased in chronically diseased livers. Our aims in the present study were to elucidate the clinical usefulness of the serum MMP-2 concentration in chronic viral liver disease. Mehods: We measured serum MMP-2 concentrations with a sandwich enzyme immunoassay in 62 patients with chronic hepatitis, 35 patients with liver cirrhosis, 55 patients with hepatocellular carcinoma and 24 healthy individuals. The assay detects proMMP-2 and proMMP-2 complexed with tissue inhibitor of metalloproteinase-2, but not active forms of MMP-2. The liver MMP-2 content was also measured in autopsied cirrhotic and non-cirrhotic livers. Gelatin zymography and gel filtration chromatography were carried out using the serum, Results The serum MMP-2 concentration was significantly increased in the liver cirrhosis and hepatocellular carcinoma patients, but not in the patients with chronic hepatitis. There was no significant difference in the serum MMP-2 level between the liver cirrhosis and hepatocellular carcinoma groups In the patients with chronic viral liver disease, serum MMP-2 concentration showed the best correlation with the degree of liver fibrosis: and with serum hyaluronate level, The zymography of serum showed the majority of MMP-2 in serum exists as a proMMP-2 The chromatography of serum revealed a single peak at the position of about 90 kDa corresponding to an MMP-2 complexed with tissue inhibitor of metalloproteinases-a, The liver MMP-2 content was markedly increased in the cirrhotic livers compared with the non-cirrhotic livers, and was positively correlated with the liver collagen content. when investigating the utility of the serum MMP-2 test for differentiating liver cirrhosis from chronic hepatitis, the utility of serum MMP-2 was equal to that of serum hyaluronate, which is known as the best current test for diagnosing liver cirrhosis, Conclusions: The serum MMP-2 concentration reflects mainly the amount of proMMP-2 complexed with tissue inhibitor of metalloproteinase-2. The serum MMP-2 level was markedly increased in cirrhotic patients, and may be explained by an overproduction in the cirrhotic liver, Tn the clinical state, the measurement of serum MMP-2 was as useful a test for diagnosing liver cirrhosis as is the serum hyaluronate level.