Predictive factors in ursodeoxycholic acid-treated patients with primary biliary Cirrhosis: Role of serum markers of connective tissue†

Abstract

The aim of this study was to define factors predictive of the onset of the terminal phase, defined by hyperbilirubinemia or the occurrence of a severe clinical complication, in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. The 97 primary biliary cirrhosis patients in this study participated in a 2-yr clinical trial. Four of the 49 patients treated with ursodeoxycholic acid (13 to 15 mg/kg/day) entered the terminal phase of the disease, compared with 9 of the 48 patients assigned to placebo. In addition to clinical, conventional biological and histological parameters, we analyzed three serum markers of connective tissue components--type III procollagen aminoterminal peptide, hyaluronic acid and laminin. In the ursodeoxycholic acid-treated group, hyaluronic acid, type III procollagen aminoterminal peptide, bilirubin and splenomegaly were the factors most closely associated with entry into the terminal phase of the disease. In multivariate analysis, after adjustment for age, the hyaluronic acid level was the only predictive factor. In the placebo-treated group, the bilirubin level, total bile acid level, Mayo score, type III procollagen aminoterminal peptide, hyaluronic acid, splenomegaly and pruritus were associated with aggravation of disease. In multivariate analysis, high bilirubin level, high type III procollagen aminoterminal peptide or hyaluronic acid levels and low prothrombin time independently implied poor prognosis. In conclusion, when patients with primary biliary cirrhosis are treated with ursodeoxycholic acid, bilirubinemia loses, in part, its predictive value. It is replaced by hyaluronic acid and type III procollagen aminoterminal peptide. This suggests that models used in deciding on the need for liver transplantation require adaptation for patients receiving ursodeoxycholic acid.

Non-Invasive Diagnostic and Prognostic Evaluation of Liver Cirrhosis and Portal Hypertension

“…In a study in patients with alcoholic liver disease [25], Nojgaard reported that YKL-40 and collagen propetide PIIINP were predictive of short survival and increased relative risk of death. In a cohort of patients with primary biliary cirrhosis treated with UDCA [26], HA was the only independent predictor of poor outcome.…”

Primary Biliary Cirrhosis

“…The best substantiated of these models relies on simple measures such as serum bilirubin and albumin levels as well as prothrombin time, the presence or absence of peripheral edema and the patients' age [5]. Similar models have been developed by other groups with some variation in the predictive variables used [131], A recent study by Pou pon et al [132] suggests that these models may need to be adjusted in patients receiving UDCA as bilirubinemia loses its predictive value, in part, in this PBC population. It is replaced by hyaluronic acid and type III pro collagen aminoterminal peptide [132], Nev ertheless, these prognostic indices may be use ful in evaluation of treatment trials and strati fication of patients entering trials as well as in the selection and timing of liver transplanta tion.…”

Correlation between Serum Hyaluronic Acid with Steatosis, Non alcoholic Steato-hepatitis and Fibrosis in Patients with Chronic Hepatitis C Virus Infection

“…8,9 Non-invasive approaches developed to assess histological samples include clinical symptoms, routine laboratory tests, and radiologic imaging. 10,11 Several clinical studies have attempted to identify serum markers that correlate with the degree of fibrosis and could thus be used in conjunction with or in place of a liver biopsy. 9,12,13 In liver, hyaluronic acid (HA) is mostly synthesized by the hepatic stellate cells and degraded by the sinusoidal endothelial cells.…”