Serum Type Iii Procollagen Peptide, Type Iv Collagen 7S Domain, Central Triple–Helix of Type Iv Collagen and Tissue Inhibitor of Metalloproteinases in Patients With Chronic Viral Liver Disease: Relationship to Liver Histology

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Abstract
To assess the clinical value of serum biochemical markers, the aminoterminal peptide of type III procollagen, type IV collagen 7S domain, the central triplehelix of type IV collagen and tissue inhibitor of metalloproteinases, as a marker of hepatic fibrosis, we measured these four serum markers in 132 patients with chronic viral liver disease and compared these serum markers with liver histological findings. Serum levels of these markers increased closely with the progress of liver disease, and the abnormal percentages of type III procollagen peptide, type IV collagen 7S domain, central triple–helix of type IV collagen and tissue inhibitor of metalloproteinases in patients with cirrhosis were 97%, 95%, 83% and 48%, respectively. These four serum markers strongly correlated with the histological degree of periportal with or without bridging hepatocellular necrosis and of liver fibrosis and correlated weakly with the degree of intralobular degeneration and focal necrosis and the degree of portal inflammation. The correlation coefficients of serum type IV collagen 7S domain with periportal with or without bridging hepatocellular necrosis and with liver fibrosis were the highest among these four serum markers, suggesting that serum type IV collagen 7S domain is the most valuable diagnostic marker to assess the degree of liver fibrosis in chronic viral liver disease. When we assessed the ability of each serum marker to detect cirrhosis with a receiver operating curve, the best test was type IV collagen 7S domain, and the second best was type III procollagen peptide. For the detection of cirrhosis, serum type IV collagen 7S domain concentration was 79% sensitive and 82% specific at a cutoff value of 8.5 ng/ml, and serum type III procollagen peptide concentration was 76% sensitive and 71% specific at a cutoff value of 1.1 U/ml. Serum central triple–helix of type IV collagen and tissue inhibitor of metalloproteinases concentrations were less accurate for the detection of cirrhosis than the other two tests. the combination of type IV collagen 7S domain and type III procollagen peptide tests had 88% sensitivity. These data suggested that the type IV collagen 7S domain test or the combination of type IV collagen 7S domain and type III procollagen peptide tests could be useful for diagnosing cirrhosis in patients with chronic viral liver disease. (Hepatology 1994;20:780-787).

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