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J Viral Hepat. 1998 May;5(3):187-92.

Serum hyaluronic acid is a useful marker of liver fibrosis in chronic hepatitis C virus infection.

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Department of Medicine, Cambridge University School of Clinical Medicine, Addenbrooke's NHS Trust, UK.


Patients with chronic hepatitis C virus (HCV) infection are often asymptomatic with few clinical signs of liver disease. Recognition of the presence of fibrosis or cirrhosis is difficult without liver biopsy, but with the availability of effective treatments, such as interferon, and the potential for progression to hepatoma in some cases, an accurate measure of the stage of disease is important. Serum hyaluronic acid (HA) has been identified as a potential marker of fibrosis or cirrhosis in other settings. In a prospective study in 130 chronic HCV carriers therefore, serum HA concentrations were compared with conventional liver function tests (including alanine aminotransferase (ALT), a-glutathione-S transferase (GST) and serum HCV RNA in order to determine which identified the stage of liver fibrosis as assessed by liver biopsy most accurately. The median HA concentrations according to the stage of fibrosis 0, 1 & 2, 3 and 4 & 5 were 17 g l-1 (range 5-37), 17 g l-1 (5-80), 30 g l-1 (10-105) and 350 g l-1 (20-800) respectively. The median HA concentration in stage 4 & 5 was significantly greater than in stages 0, 1 & 2 or 3. Serum HA concentration rose with age, but even when adjusted for age the median HA at stage 4 & 5 was greater than all other groups (95% CI of difference between the medians exceeded 0). Thus, serum HA gave a sensitivity and specificity for stage 4 & 5 fibrosis of 85% and 88% respectively, exceeding those for ALT or GST. In contrast, serum ALT or GST levels were not correlated with the stage of fibrosis although ALT was significantly greater in the cirrhotic group when compared to the group with no fibrosis (stage 0). There was no correlation between serum HA and either the grade of inflammatory changes or serum HCV RNA. These results suggest that serum hyaluronic acid is a useful marker of liver fibrosis in patients with chronic HCV infection. It could therefore be used to monitor patients at risk of progressive fibrosis, in controlled clinical trials, as a measure of response to antifibrotic therapy and in those in whom liver biopsy is difficult or contraindicated.

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