Expression of matrix metalloproteinase-2 and-9 and their inhibitors in peripheral blood cells of patients with chronic hepatitis C

Background: To clarify whether circulating matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) can be used as serum markers of fibrop roliferation in chronic liver diseases, we studied the expression of MMP-2 and MMP-9 in relation to TIMP-1 and TIMP-2 in peripheral blood mononuclear leukocytes (MNLs) and polymorphonuclear leukocytes (PMLs), and compared thi s expression to circulating concentrations and hepatic histology in patient s with chronic active hepatitis C (CAH). Methods: Quantitative reverse transcription-PCR/ELISA assays were performed for MMP and TIMP RNA, and Corresponding circulating protein concentrations were studied by ELISA in 20 healthy controls, 40 patients with CAH, and 20 patients with hepatitis C-induced cirrhosis (Ci). Results: MMP-2 mRNA was found almost exclusively in the: liver, MMP-9 mRNA in leukocytes. TIMP RNA-equivalents were decreased in MNLs of CAH patients, but neither MMP-9 nor TIMP RNA expression showed any correlation to the ex tent of inflammation and fibrosis. MMP-2 and TIMP-1 protein concentrations were increased in Ci patients and showed a wide overlap in CAH patients and healthy controls. MMP-9 values were lower; in CAH and Ci patients than in healthy controls. TIMP-2 values showed a wide overlap in all three groups. The MMP-2/TIMP-1 and MMP-9/TIMP-1 ratios were lower in Ci patients than in healthy controls; the MMP-2/TIMP-2 and MMP-9/TIMP-2 ratios were not differe nt Circulating TIMP-1 and the MMP-2/TIMP-1 ratio-correlated to the inflamma tory activity in liver biopsies, but only the circulating MMP-2/TIMP-1 rati o also correlated with the degree of fibrosis. Conclusions: Peripheral blood cell expression of MMP-2, MMP-9, and TIMP rev ealed no correlation with the circulating concentrations of these proteins. Only the circulating MMP-2/TIMP-1 ratio correlated to the histological deg ree of fibrosis in hepatitis C and should be further evaluated as a progres sion marker in patients with chronic liver disease. (C) 2000 American Assoc iation for Clinical Chemistry.