Alterations in bilirubin metabolism during extra- and intrahepatic cholestasis.

This study was performed to investigate modifications in the serum bilirubin forms, hepatobiliary enzymes, and some glycoproteic substances in patients during the course of extrahepatic cholestasis (stage A) and following its clinical resolution (stage B). The series consisted of 16 patients: 11 had main bile duct stones; two, benign stenosis of the main bile duct; and three, main bile duct cancer. Cholestasis resolved spontaneously in one case, under endoscopy in two, and following surgery in 13. Five patients with liver cirrhosis and a picture of intrahepatic cholestasis following anesthesia were also investigated. Serum bilirubin forms were measured using van den Bergh's method and the alkaline methanolysis-HPLC procedure; the mono- and di-conjugated forms were considered together in the overall evaluation of the results. The hepatobiliary enzymes (ALP, GGT, and AST) were increased at stage A and significantly decreased at stage B. Similar patterns were observed in total (TB), unconjugated (UB), and conjugated bilirubin (CB) and in the percentage of CB out of TB (% CB). In the majority of patients, % CB at stage B was lower than at stage A, whereas in subjects with a high initial UB value, a different % CB pattern was observed. The direct bilirubin percentage (% DB), on the other hand, had a different pattern, and the variations between stages A and B were not significant. The pathophysiological bilirubin pattern was similar in patients with intrahepatic cholestasis. At stage A, in a number of patients the levels of glycoproteic substances (CA 19-9, TPA and ferritin) were raised, but at stage B they tended to decrease towards the normal range. Correlations were found between CA 19-9 or TPA variations and cholestasis indicators. It may be concluded that our HPLC technique may reveal differences in the behavior of the bilirubin pigments that cannot be detected with van den Bergh's method, even in the presence of similar TB variations. The increase in the glycoproteic substances considered may express an impairment in their metabolic (largely hepatic) clearance, as occurs in the cholestatic setting.