Hyaluronic acid predicts hepatic fibrosis in children with hepatic disease

Background: Hyaluronic acid (HA) is removed by the liver via sinusoidal cell adhesion molecules. This is impeded in fibrosis, leading to a rise in serum HA. As a noninvasive marker of fibrosis, HA may obviate the need for liver biopsy. Objective: To evaluate HA as a marker of hepatic fibrosis, in unselected children undergoing liver biopsy. Methods: Ninety-three unselected consecutive children (median age, 7.5 years: range, 0.07-19 years) undergoing a liver biopsy between April 2003 and March 2004 were prospectively recruited. Liver biopsy and fasting HA levels were taken simultaneously. The Ishak score was used to stage fibrosis. Scores of 3 or greater were regarded as significant fibrosis. Hyaluronic acid levels were measured using an enzyme-linked binding protein assay (2002 Corgenix, Inc) (adult reference range, 0-75 ng/mL; pediatric reference range, 0-30 ng/mL). Results: Twenty-three (25%) of 93 biopsies had significant fibrosis, and HA levels in this group were significantly higher than those with mild fibrosis (Ishak score, < 3), (median level, 72 ng/mL vs 30 ng/mL; Mann-Whitney U test; P < 0.005). Hyaluronic acid level of 50 ng/mL had a positive predictive value 40% and negative predictive value 86% for significant fibrosis. An HA level 200 ng/mL has a sensitivity of 26% and specificity of 90%. Conclusions: Hyaluromic Acid is a valid noninvasive predictor of hepatic fibrosis in unselected children with liver disease. An HA level of 200 ng/mL strongly suggests significant fibrosis. Hyaluronic acid level of less than 50 ng/mL accurately identifies those who do not have significant fibrosis.