Diagnostic value of serum markers of connective tissue turnover for predicting histological staging and grading in patients with chronic hepatitis C

Purpose. Chronic hepatitis C is an insidiously progressive disease, in which repeated assessment of liver histology is required. Various serum fibrotic markers have now been introduced. Our present aim was to assess, by receiver operating characteristic analysis, the usefulness of serum fibrotic markers for diagnosing fibrotic staging and necroinflammatory grading in chronic hepatitis C. Methods. Serum levels of procollagen type III N-terminal peptide (PIIINP), 7S fragment of type IV collagen (PIVNP), hyaluronan (HA), matrix metallo-proteinase (MMP)-1, MMP-2, and tissue inhibitor of metalloproteinases (TIMP)-1 were measured in 169 patients with chronic hepatitis C. Results. The accuracy of these tests for discriminating stages greater than F2 from stages less than FI was superior to that for discriminating stage F3 from stages less than F2. The most useful test for predicting stages greater than F2 was the serum HA test (cutoff value, 50 ng/ml; sensitivity, 75%; specificity, 80%), and the next-most useful was the serum MMP-2 test (cutoff value, 550 ng/ml; sensitivity, 75%; specificity, 70%). The usefulness of these tests for discriminating moderate grade from grades less than mild was superior to that for discriminating grades more than mild from minimal grade. The most useful test for predicting moderate grade was the serum HA test (cutoff value, 60 ng/ml; sensitivity, 77%; specificity, 74%), and the second-most useful was the serum PIVNP test (cutoff value, 6.5 ng/ml; sensitivity, 74%; specificity, 75%). The combination of the most useful and next-most useful test results increased the accuracy of the diagnosis of staging and grading. Conclusions. These serum fibrotic markers, especially the serum HA test, would be clinically useful for assessing staging and grading in patients with chronic hepatitis C.