Abstract
Following studies in animal models of hepatotoxicity four enzymes were selected for investigation as indices of hepatic function in human disease. Isocitrate dehydrogenase, alanine aminotransferase, aspartate aminotransferase and glycyl prolyl-p-nitroanilidase activities were investigated in patients with hepatobiliary disease. Isocitrate dehydrogenase appeared to be a sensitive and specific index of hepatocellular damage. The serum activity of glycyl prolyl-p-nitroanilidase was markedly increased in all hepatobiliary diseases studied. Although it has become customary practice to use plasma enzyme activities, such as aspartate aminotransferase and alkaline phosphatase, as the biochemical parameters of choice for assessment of liver damage, these enzymes are not true indicators of liver function. Indeed, increased plasma concentrations of the aminotransferases, gamma-glutamyltransferase and other hepatocellular enzymes, may reflect only increased permeability of the hepatocyte plasma membranes, enzyme induction, or reversible hepatocellular damage. In the safety evaluation of drugs there is a real need to be able to evaluate liver function with greater reliability. There have been many instances in recent years, when the use of plasma enzyme levels as liver function tests have failed to detect drug-induced hepatotoxicity or to the contrary have given false indications of potential liver damage. Measurement of the serum concentration of prealbumin, a protein of short half life, synthesised and secreted by the liver into the blood, is a true test of hepatic function. Concentrations of prealbumin have been determined in the serum of patients with hepatobiliary disease and also in patients who have taken an overdosage of paracetamol. Concentrations of this protein have also been assessed in the serum of mice treated with hepatotoxins. Prealbumin appears to be a sensitive index of impaired liver function in human hepatobiliary disease and drug toxicity and also in animals treated with hepatotoxic chemicals. This protein may ultimately be of great value in the safety evaluation of new drugs and also as a prognostic tool following the overdosage of hepatotoxic drugs.