Comparison of assays for N-amino terminal propeptide of type III procollagen in chronic hepatitis C by using receiver operating characteristic analysis

Abstract

OBJECTIVE: During the process of liver fibrosis, type III procollagen is converted to type III collagen by cleavage of its amino terminal and carboxy terminal propeptides. Serum levels of amino terminal propeptide of type III procollagen (PIIINP) are a marker of collagen turnover in liver fibrosis. Two assays for PIIINP are available, one which measures both Col 1-3 (collagen synthesis) and Col 1 (collagen degradation) peptides, and one which measures Col 1-3 only. Using receiver operating characteristic analysis, the two PIIINP assays were compared with serum ALT as markers of liver disease in chronic hepatitis C. METHODS: Serum PIIINP was measured using both assays in 33 patients with chronic hepatitis C and five healthy controls. Liver biopsies in chronic hepatitis C patients were scored using a previously described grading and staging system. RESULTS: Serum PIIINP was significantly elevated in chronic hepatitis C compared to controls using both the combined Col 1-3 and Col 1 (median 0.61 vs 0.33 U/ml, P=0.001) and Col 1 assays (median 6.5 vs 3.5 microg/l, P=0.006). Serum PIIINP measured by the combined assay was significantly related to liver fibrosis, periportal necrosis and histological activity index (P<0.05). The area under the curve for specificity and sensitivity in detecting advanced liver disease was only significant for the combined assay (P=0.017). Serum PIIINP measured by the Col 1 assay was not related to these indices of disease severity while serum ALT was only related to portal inflammation. CONCLUSION: A serum PIIINP assay which measures both Col 1-3 and Col 1 peptides instead of Col 1-3 peptide alone is more predictive of severity of liver disease and should be used in preference as a non-invasive marker of liver injury in chronic hepatitis C.