Circulating Matrix Metalloproteinases 1, 2, 9 and Their Inhibitors TIMP-1 and TIMP-2 as Serum Markers of Liver Fibrosis in Patients With Chronic Hepatitis C: Comparison With PIIINP and Hyaluronic Acid

Leroy, Vincent; Monier, Frederique; Bottari, Serge; Trocme, Candice; Sturm, Nathalie; Hilleret, Marie-Noëlle; Morel, Francoise; Zarski, Jean-Pierre
February 2004
American Journal of Gastroenterology;Feb2004, Vol. 99 Issue 2, p271
Academic Journal
OBJECTIVES: Histological examination of liver biopsy is currently required in the management of patients with chronic hepatitis C. Our aim was to evaluate thediagnostic utilityof a panel of circulating markers in detecting the stage of fibrosis.METHODS: One hundred and ninety four-patients who had undergone a percutaneous liver biopsy before antiviral treatment, and 194 age- and sex-matched healthy subjects were studied. Serum levels of hyaluronate, procollagen type IIIN-terminal peptide (PIIINP), matrix metalloproteinases (MMP)-1, MMP-2, MMP-9 and their tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 were determined by RIA and ELISA. Histological lesions were staged according to the METAVIR score.RESULTS: Hyaluronate, PIIINP, TIMP-1, and TIMP-2 serum levels were significantly higher in patients than in controls. Six markers were significantly correlated with fibrosis: MMP-2 (r= 0.28;p<0.01), TIMP-1 (r= 0.42;p<0.001), HA (r= 0.50;p<0.001), PIIINP (r= 0.62;p<0.0001), MMP-1 (r=−0.32;p<0.01), and MMP-9 (r= −0.22;p<0.05). By multivariate analysis, only PIIINP and MMP-1 were independently associated with fibrosis, and were combined using the equation of the logistic regression model. Using receiver-operating characteristics analysis, the area under the curve of the score to discriminate mild (F0/F1) from significant fibrosis (F2/F3/F4) was 0.82, with a sensitivity of 60% for a specificity of 92%.CONCLUSION: Our results suggest that combining two serum markers reflecting fibrogenesis (PIIINP) and fibrolysis (MMP-1) may provide a useful tool for evaluating liver fibrosis.


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