Clinical usefulness of serum tissue inhibitor of metalloproteinases (TIMP)-2 assay in patients with chronic liver disease in comparison with serum TIMP-1

Tissue inhibitors of metalloproteinases (TIMPs) are involved in liver fibro sis through impaired matrix degradation. Previous studies showed that the s erum level of TIMP-1 was increased in patients with chronic liver disease, reflecting the liver TIMP-1 level, and that it is useful for assessing live r fibrosis. An enzyme immunoassay for TIMP-2 is now available. In this stud y, we examined the clinical usefulness of this serum TIMP-2 test for liver fibrosis in patients with chronic liver disease, in comparison with the ser um TIMP-1 test. The serum TIMP-2 concentration was 61+/-13 ng/ml in healthy controls (n = 32), and 18% higher in the group of chronic active hepatitis (CAH) patients (n = 34), 64% higher in the liver cirrhosis (LC) group (n = 33) and 44% higher in the hepatocellular carcinoma (HCC) group (n = 61), a nd similar to the control level in the chronic persistent hepatitis (CPH) g roup (n = 23). In contrast, the serum TIMP-1 concentration was 155+/-17 ng/ ml in the healthy controls, 18% higher in CPH, 35% in CAH, 63% higher in LC and 92% higher in HCC. The serum TIMP-2 level was related to the histologi cal degrees of both periportal necrosis and liver fibrosis, as well as to t he serum TIMP-1 level. However, the relationships for TIMP-2 were weaker co mpared to those of serum TIMP-1. These results suggest that compared to the serum TIMP-1 level, changes in the serum TIMP-2 level in chronic liver dis ease are less liver-specific, and the serum TIMP-2 level is less useful in the assessment of liver fibrosis in chronic liver disease. (C) 1999 Elsevie r Science B.V. All rights reserved.