Serum tissue inhibitor of metalloproteinases in patients with chronic liver disease and with hepatocellular carcinoma.

To examine the clinical significance of serum level of tissue inhibitor of metalloproteinases (TIMP) in chronic liver disease and in hepatocellular carcinoma, we measured serum TIMP concentration by a sandwich enzyme immunoassay in 79 patients with chronic liver disease and 49 patients 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 cirrhosis. Serum TIMP level was closely correlated with serum level of type IV collagen 75 domain and with the histological degree of liver fibrosis in chronic liver disease. Serum TIMP level in hepatocellular carcinoma was increased 2.3-fold compared with that in controls, and was significantly higher than in liver cirrhosis. Serum TIMP level increased with tumor size, and significantly correlated with serum alpha-fetoprotein level. Gel filtration on Sephadex G-75 showed that the TIMP in serum was present as an enzyme-complexed form. These results suggest that the measurement of serum TIMP concentration is useful in the clinical assessment of liver fibrosis in chronic liver disease and of the development of hepatocellular carcinoma.