Serum matrix metalloproteinase-1 in patients with chronic viral hepatitis

Background and Aims: Previously we found that serum matrix metalloproteinase (MMP)-1 activity decreased with progression of chronic liver disease. Our objectives in the present study were to observe the change in the serum MMP-1 protein concentration using recently developed specific enzyme immunoassays for MMP-1 and MMP-1 complexed with tissue inhibitor of metalloproteinases (TIMP)-1 and to elucidate the clinical usefulness of the serum MMP-1 test in chronic viral hepatitis. We measured the serum concentrations of MMP-1 and MMP-1/TIMP-1 complex using these immunoassays in 64 patients with histologically characterized chronic viral hepatitis. Results: Serum MMP-1 concentration was inversely related to the histological severity of chronic hepatitis (P < 0.0001). It was closely associated with the histological degree of peripartal necrosis (P < 0.0001), intralobular necrosis (P < 0.005), portal inflammation (P < 0.0001) and liver fibrosis (P < 0.05). The serum concentration of MMP-1/TIMP-1 complex was also related tu the histological severity of chronic hepatitis (P < 0.0001). It was associated with the degree of portal inflammation (P < 0.05), but not with the degree of periportal necrosis, intralobular necrosis or liver fibrosis. As serum MMP-1 level was closely associated with the histological degree of necroinflammation, we examined the ability of the serum MMP-1 test to differentiate active and inactive forms of hepatitis with a receiver operating curve. The results were compared with those of serum procollagen type III N-peptide (PIIINP) test. We found that the serum MMP-1 test was superior to the serum PIIINP test in assessing liver necroinflammation. Conclusions: In addition to the previously reported changes in enzyme activity, MMP-1 proteins in serum decreased during histological progression of chronic hepatitis. The serum MMP-1 test may be useful clinically to differentiate active and inactive types of hepatitis in patients with chronic viral hepatitis.