SERUM TISSUE INHIBITOR OF METALLOPROTEINASES IN PATIENTS WITH CHRONICLIVER-DISEASE AND WITH HEPATOCELLULAR-CARCINOMA

To examine the clinical significance of serum level of tissue inhibito r of metalloproteinases (TIMP) in chronic liver disease and in hepatoc ellular carcinoma, we measured serum TIMP concentration by a sandwich enzyme immunoassay in 79 patients with chronic liver disease and 49 pa tients with hepatocellular carcinoma. Serum TIMP concentration was 164 +/- 20 ng/ml in healthy controls, and was 10% higher than control in chronic persistent hepatitis, 36% higher in chronic active hepatitis, 62% higher in liver cirrhosis and 30% higher in primary biliary cirrho sis. Serum TIMP level was closely correlated with serum level of type IV collagen 75 domain and with the histological degree of liver fibros is in chronic liver disease. Serum TIMP level in hepatocellular carcin oma was increased 2.3-fold compared with that in controls, and was sig nificantly higher that in liver cirrhosis. Serum TIMP level increased with tumor size, and significantly correlated with serum alpha-fetopro tein level. Gel filtration on Sephadex G-75 showed that the TIMP in se rum was present as an enzyme-complexed form. These results suggest tha t the measurement of serum TIMP concentration is useful in the clinica l assessment of liver fibrosis in chronic liver disease and of the dev elopment of hepatocelluar carcinoma.