SERUM HYALURONAN AS A MARKER OF LIVER FIBROSIS IN CHRONIC VIRAL HEPATITIS-C - EFFECT OF ALPHA-INTERFERON THERAPY

Background/Aims: It has been suggested that increases in serum hyaluronan levels might be a marker of fibrosis in chronic viral hepatitis C. Patients receiving alpha-interferon therapy are an excellent model to determine the relationship between serum hyaluronan and liver fibrosis, since results suggest that alpha-interferon could reduce liver fibrosis. Methods: We studied the relationship between serum hyaluronan and histopathological indices of liver fibrosis, inflammation and necrosis, before and after alpha-interferon therapy (3 MU, three times weekly for 6 months), and the effect of treatment on serum hyaluronan and on histological liver fibrosis, in 52 patients, Hyaluronan levels were measured using a radiometric assay and the liver histopathological indices were scored according to the Knodell system. Results: The serum hyaluronan level correlated with the extent of liver fibrosis both before and after alpha-interferon therapy (p<0.0001), but not with the histo-pathological indices of liver inflammation or necrosis, Parallel changes in serum hyaluronan and liver fibrosis occurred: serum hyaluronan levels fell significantly in patients in whom fibrosis improved (p<0.01, n=11), increased significantly in patients in whom fibrosis worsened (p<0.05, n=10), and did not change significantly in patients in whom fibrosis was unmodified (n=31), Furthermore, fibrosis improved only when the antiviral effect of alpha-interferon was reflected by persistent normalization of serum alanine aminotransferase, although there was no correlation between serum hyaluronan levels and alanine aminotransferase activities. Conclusion: Serum hyaluronan thus appears to be a non-invasive index of liver fibrosis.