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


METHODS
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-2. 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. In the clinical state, the measurement of serum MMP-2 was as useful a test for diagnosing liver cirrhosis as is the serum hyaluronate level.
Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Y
Y
Murawaki
S
S
Yamada
Y
Y
Ikuta
H
H
Kawasaki
D015415:Biomarkers / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis; D004792:Enzyme Precursors / Q000097:blood; D005260:Female; D018093:Gelatinases / Q000097:blood*; D006521:Hepatitis, Chronic / Q000175:diagnosis; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D007124:Immunoenzyme Techniques; D008099:Liver / Q000201:enzymology; D008103:Liver Cirrhosis / Q000175:diagnosis; D008107:Liver Diseases / Q000175:diagnosis*; D008113:Liver Neoplasms / Q000175:diagnosis; D008297:Male; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000097:blood*; D008875:Middle Aged; D014777:Virus Diseases / Q000175:diagnosis*
D015415:Biomarkers; D004792:Enzyme Precursors; D006820:Hyaluronic Acid; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2