Serum parameters of liver fibrosis

Chronic liver disease is often associated with deposition of fibrous tissue, a process which together with the destruction of normal liver and liver cell regeneration, leads to the condition called cirrhosis. Cirrhosis is known to be associated with a reduction in life expectancy. In recent years there has been an increasing interest in the pathogenesis of cirrhosis and in the possibilities reversing the process of fibrogenesis. Liver biopsy is the present "gold standard" for detecting the presence of fibrosis and cirrhosis, but is not suitable for evaluating the dynamics of pathological fibrogenesis. The aim of this thesis was to study serological markers of connective tissue metabolism as non-invasive tests of liver fibrosis and cirrhosis. We studied procollagen type Ill aminoterminal peptide and the P1 fragment of lam in in as possible serum markers of fibrosis in alcoholic cirrhosis, primary biliary cirrhosis and after liver transplantation. The value of procollagen type Ill aminoterminal peptide for predicting histological progression of primary biliary cirrhosis was investigated. A new radioimmunological technique, based on a so-called "coated tube" method, for determination of procollagen type Ill aminoterminal peptide was tested and compared with the conventional radioimmunoassay. The clinical value of N-acetyi-~-D-glucosaminidase as a marker of fibrosis and liver disease was evaluated. Concomitantly with the investigation of these serum markers of fibrosis, we performed a study on the prognosis of patients with alcoholic liver cirrhosis. The main reason for performing the study was to determine what the prognosis of alcoholic cirrhosis was in The Netherlands, and to determine whether features which have been described to have prognostic implications in other countries also apply in the local population.