Aminoterminal propeptide of type III procollagen and hyaluronan in patients with primary biliary cirrhosis: markers of fibrosis in primary biliary cirrhosis.

Abstract

The aminoterminal propeptide of type III procollagen (PIIINP) and hyaluronan have previously been studied in different liver diseases. The results of these studies are controversial. The aim of the present study was to examine the relationship between PIIINP and hyaluronan levels and the clinical, biochemical and histological features of primary biliary cirrhosis (PBC) and its prognosis. Fifty-five PBC patients were studied at the time of diagnosis of PBC and were followed up for a mean of 58 months. During the follow-up period 21 patients died. In addition, 30 healthy subjects were examined in the present study. Hyaluronan and PIIINP were measured by radioimmunoassay and the levels of both PIIINP and hyaluronan were higher in PBC patients than in healthy volunteers (P < 1.8 x 10(-6) and 1.6 x 10(-9), respectively). Hyaluronan and PIIINP levels were above normal values in 82 and 84% of PBC patients, respectively. There were correlations between PIIINP and hyaluronan and the histological stage of PBC (r = 0.44, P < 0.004 and r = 0.56, P < 0.00001, respectively). The correlation between PIIINP and hyaluronan was 0.46 (P < 0.0035). In symptomatic patients, both PIIINP and hyaluronan values were higher than in controls (P < 0.002 and P < 0.006, respectively). The levels of PIIINP correlated significantly with bilirubin (r = 0.43, P < 0.006), while hyaluronan was correlated with age (r = 0.33, P < 0.015), pruritus (r = 0.32, P < 0.02), fatigue (r = 0.41, P < 0.003), hepatomegaly (r = -0.46, P < 0.0008), the presence of oesophageal varices (r = 0.34, P < 0.002), weight loss (r = 0.29, P < 0.05), bilirubin (r = 0.54, P < 0.0001), albumin (r = -0.30, P < 0.04), extent of fat excretion (r = 0.53, P < 0.009) and length of symptomatic period before diagnosis of PBC (r = 0.43, P < 0.002). Using Cox's logistic regression analysis, survival was found to be influenced by bilirubin concentration but not by hyaluronan, PIIINP, age, albumin or histological stage. Therefore, hyaluronan is a more sensitive marker for predicting advanced PBC than is PIIINP. However, neither hyaluronan nor PIIINP gave any indication of prognostic outcome.