Diagnostic accuracy of serum hyaluronic acid, FIBROSpect II, and YKL-40 for discriminating fibrosis stages in chronic hepatitis C

OBJECTIVES: Noninvasive serum markers of liver fibrosis are being used as an alternative to liver biopsy. Currently available tests distinguish, with accuracy, only absent/minimal fibrosis (Ishak stages 0-1) and advanced fibrosis/cirrhosis (Ishak stages 4-6), but not intermediate fibrosis (Ishak stages 2-3). Our aim was to evaluate the diagnostic accuracy of hyaluronic acid (HA), FIBROSpect II (FS-II), and YKL-40 (chondrex, human cartilage glycoprotein-39) in various clinically important categories of fibrosis, and further correlate these serum markers with digital quantification of fibrosis (DQF) and Ishak stages. METHODS: Serum HA, YKL-40, and FS-II were retrospectively assessed and correlated with Ishak stages and DQF scores in 75 patients with chronic hepatitis C (HCV). Spearman's rho statistics assessed relationships among all parameters, and receiver operator characteristic curves evaluated accuracy of each parameter when compared to the Ishak stages. RESULTS: All three serum markers and DQF correlated highly with one another (P <= 0.01) and with Ishak stages of fibrosis. Among the serum markers, HA was effective in discriminating between Ishak stages 0-1 and Ishak stages 2-3 compared with FS-II, with an area under the curve of 0.76 versus 0.66 and a false-positive rate of 0.33 versus 0.67, respectively. All three serum markers predicted advanced fibrosis and cirrhosis. YKL-40 had the highest false-positive rates in all categories of fibrosis. CONCLUSIONS: HA can be utilized as a reliable surrogate marker in distinguishing three clinically relevant stages of fibrosis: absent/minimal, intermediate, and advanced/cirrhosis. HA should be considered as a cost-effective alternative to other serum markers for staging fibrosis and for determining the timing and selection of HCV treatment.