TISSUE INHIBITOR OF METALLOPROTEINASE-1 IN THE LIVER OF PATIENTS WITHCHRONIC LIVER-DISEASE

Background/Aims: Tissue inhibitor of metalloproteinase (TIMP)-1 is an important regulator of matrix metalloproteinase activity. To clarify t he changes in TIMP-1 in diseased livers, we measured TIMP-1 concentrat ions in liver tissue samples from patients with chronic liver disease, The relationship between serum and liver levels of TIMP-1 was also ex amined in some patients. Methods: The subjects were 68 patients who un derwent liver biopsy The liver TIMP-1 concentration was measured using an enzyme immunoassay after the extraction of TIMP-1 with 2 M guanidi ne. Results: As compared with the controls (n = 10), the liver TIMP-1 level was increased 2.2-fold in the 24 chronic active hepatitis 2A pat ients, 2.9-fold in the 10 chronic active hepatitis 2B patients and 4.1 -fold in the six liver cirrhosis patients, but no significant increase was observed among the 18 chronic persistent hepatitis patients, The liver TIMP-1 levels mere closely correlated with the histological degr ees of periportal necrosis, portal inflammation, and liver fibrosis, W hen the localization of TIMP-1 was examined immunohistochemically, TIM P-1 was stained mainly in hepatocytes, and the intensity was stronger in the livers of chronic active hepatitis and liver cirrhosis patients than in those of the chronic persistent hepatitis patients, The serum TIMP-1 and liver TIMP-1 levels were significantly correlated, indicat ing that serum TIMP-1 could reflect the change of liver TIMP-1 in pati ents with chronic liver disease. Conclusion: Liver TIMP-1 concentratio n increases with progression of the liver disease, when the degradatio n of extracellular matrix proteins is decreased, resulting in the deve lopment of liver fibrosis.