Tissue inhibitor of metalloproteinase is increased in the serum of precirrhotic and cirrhotic alcoholic patients and can serve as a marker of fibrosis.
One of the contributory factors to the development of cirrhosis is a decrease in collagenase activity, which may be related to levels of inhibitors such as serum tissue inhibitor of metalloproteinase. We therefore measured serum tissue inhibitor of metalloproteinase and serum procollagen III peptides (another proposed marker of fibrosis) in 16 healthy controls and 44 alcoholic patients with biopsy-proved liver disease, namely steatosis without fibrosis (n = 13), perivenular fibrosis (n = 10), septal fibrosis or cirrhosis or both (n = 15) and alcoholic hepatitis (n = 6). In alcoholic patients, serum tissue inhibitor of metalloproteinase values strongly correlated with fibrosis (rs = 0.70, p < 0.001). Compared with values in controls (177 +/- 12 ng/ml), serum tissue inhibitor of metalloproteinase was significantly elevated in perivenular fibrosis (330 +/- 22 ng/ml, p < 0.05), in septal fibrosis, cirrhosis or both (406 +/- 29 ng/ml, p < 0.001) and in alcoholic hepatitis (526 +/- 140 ng/ml, p < 0.001) but not in steatosis (204 +/- 17 ng/ml). In contrast, procollagen III peptides were significantly increased only in the septal fibrosis-cirrhosis group but not in the perivenular fibrosis group. With the threshold defined as the upper value of the steatosis group (resulting in a specificity of 100%), we found that serum tissue inhibitor of metalloproteinase was elevated in 50% of patients with perivenular fibrosis, in 87% of subjects with extensive fibrosis (septal fibrosis, cirrhosis or both) and in 67% of individuals with alcoholic hepatitis. The overall sensitivity of serum tissue inhibitor of metalloproteinase for detecting either perivenular fibrosis or more extensive fibrosis was 71%.(ABSTRACT TRUNCATED AT 250 WORDS)
Li
J
J
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, New York 10468.
Rosman
A S
AS
Leo
M A
MA
Nagai
Y
Y
Lieber
C S
CS
D000328:Adult; D000437:Alcoholism / Q000097:blood / Q000175:diagnosis*; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D005235:Fatty Liver, Alcoholic / Q000097:blood / Q000175:diagnosis; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006525:Hepatitis, Viral, Human / Q000097:blood; D006801:Humans; D008099:Liver / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D012372:ROC Curve; D019714:Tissue Inhibitor of Metalloproteinases
D015415:Biomarkers; D006023:Glycoproteins; D010446:Peptide Fragments; D011347:Procollagen; D019714:Tissue Inhibitor of Metalloproteinases; C041876:procollagen Type III-N-terminal peptide; D008666:Metalloendopeptidases