Hepatic collagen proline hydroxylase activity in alcoholic hepatitis: effect of d-penicillamine

Hepatic collagen proline hydroxylase activity was measured in the presence of Triton X-100 in 80 patients with alcoholic liver disease. The mean enzyme activity was elevated only in patients with alcoholic hepatitis and not in those with fatty infiltration or inactive cirrhosis. Elevations of the urinary excretion of peptide-bound hydroxyproline and glycosaminoglycans were found in patients with alcoholic hepatitis and inactive cirrhosis. In patients with alcoholic hepatitis with initial elevation of enzymes values (greater than the mean control value plus 2 S.D., >171 dpm/mg of protein per minute), there was a further increase in the enzyme in four of five patients receiving placebo, but a fall in all three receiving d-penicillamine, 1.0 gm/day, for a period of 1 month. However, no significant changes were found in the mean activity of the enzyme in the entire group of patients with alcoholic hepatitis after the administration of either placebo or d-penicillamine. The urinary excretion of peptide-bound hydroxyproline decreased in patients receiving placebo but not in those receiving d-penicillamine; the urinary excretion of glycosaminoglycans was not changed by either treatment. These studies show that among alcoholic patients with liver disease, those with alcoholic hepatitis have the greatest changes in parameters of collagen metabolism. In patients with alcoholic hepatitis, d-penicillamine appears to suppress elevated values of collagen proline hydroxylase while preventing decreases in the urinary excretion of peptide-bound hydroxyproline found with the administration of placebo. This suggests that d-penicillamine may decrease augmented hepatic collagen synthesis.