Prognostic value of serum hyaluronan in patients with compensated HCV cirrhosis

Background/Aim: Serum hyaluronan (HA) levels increase according to the degree of liver fibrosis in patients with chronic viral hepatitis C. Patients with liver disease and markedly high serum HA levels have cirrhosis with typical signs of hepatic sinusoidal capillarization, a factor of aggravation of cirrhosis. The aim of this study was to evaluate the prognostic value of serum HA for severe complications in asymptomatic patients with HCV cirrhosis. Methods: Six hundred and sixty-eight patients with anti-HCV antibodies and increased serum alanine aminotransferase were referred to our hospital for evaluation, including liver biopsy. At entry, serum HA levels were measured in 91 patients (64 men, 27 women, 56+/-11 years old) out of 103 who had asymptomatic, biopsy-proven cirrhosis. According to the criteria of Child-Pugh, 82 were classified A and 9 B. The follow-up period was 6 to 82 months (median: 38 months), and 51 of these patients received alpha-interferon therapy during the first year. Severe comlplications were defined as death or liver transplantation, ascites, bleeding from esophageal varices, encephalopathy, or hepatocellular carcinoma. Results: Serum HA levels at entry were higher in the cirrhotic patients in whom severe complications occurred during the follow-up period (520+/-426 mu g/l vs. 197+/-146 mu g/l, p<0.0001). The patients with serum hyaluronan levels >350 mu g/l displayed higher probabilities of occurrence of severe complications (p<0.0001). Other factors associated with the occurrence of complications or death were: serum bilirubin >18 mu mol/l (p=0.03), platelet count <112x10(9)/l (p=0.02), prothrombin time <63% (p<0.0001), serum albumin <36 g/l (p=0.002), alkaline phosphatase >81 IU/l (p=0.01), and no interferon treatment (p=0.0003). Multivariate analysis identified five independent factors predictive of severe clinical complications, namely: hyaluronan (p=0.006), prothrombin time (p=0.04), bilirubin (p=0.04), albumin (p=0.04), and no therapy (p=0.03). Conclusion: Serum HA level is predictive for occurrence of severe complications in HCV cirrhosis, and can be used as a prognostic marker, in addition to the parameters of the Child-Pugh score, particularly in patients with compensated cirrhosis.