Serum matrix metalloproteinase-1 in patients with chronic viral hepatitis.
OBJECTIVE
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 periportal 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 to 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.
Murawaki
Y
Y
Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Ikuta
Y
Y
Idobe
Y
Y
Kawasaki
H
H
D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D017364:Collagenases / Q000097:blood*; D018450:Disease Progression; D005260:Female; D019694:Hepatitis B, Chronic / Q000201:enzymology* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020781:Matrix Metalloproteinase 1; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D012372:ROC Curve; D011863:Radioimmunoassay; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; D019715:Tissue Inhibitor of Metalloproteinase-1; C041876:procollagen Type III-N-terminal peptide; D017364:Collagenases; D020781:Matrix Metalloproteinase 1