Hepatic prolyl hydroxylase and collagen synthesis in patients with alcoholic liver disease

Abstract

Hepatic prolyl hydroxylase activity and collagen synthesis were measured in patients with alcoholic liver disease to determine the feasibility of using the enzyme prolyl hydroxylase as a marker of hepatic fibrogenesis. Alcoholic patients with liver histopathology consistent with normal, steatosis, alcoholic hepatitis, early cirrhosis, or advanced cirrhosis were analysed for liver prolyl hydroxylase activity and in vitro collagen synthesis. Prolyl hydroxylase activity and the rate of in vitro collagen synthesis were correlated when these parameters were measured in samples of the same liver biopsy. Mean prolyl hydroxylase activity was significantly raised in all groups of alcoholic patients with alcoholic liver disease, except those with steatosis, when compared with alcoholic patients with normal morphology. Alcoholic patients with early cirrhosis had enzyme activity (mean ± SE: 1.367±0.162 mU/mg protein) significantly raised over all other groups. Mean enzyme activity was less raised (0.985±0.097 mU/mg protein) in patients with advanced cirrhosis. The percentage of collagen synthesis in patients with early or advanced cirrhosis was also raised compared with alcoholic patients with normal morphology. Prolyl hydroxylase activity and the rate of collagen synthesis are significantly correlated (r=0.62). These findings suggest that hepatic prolyl hydroxylase activity is a useful indicator of hepatic fibrogenesis and its measurement on available liver biopsy tissue should be a potent diagnostic tool reflecting active fibrogenesis and predicting progression of alcoholic liver disease.