Summary
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, 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.
Similar content being viewed by others
Abbreviations
- TB:
-
total bilirubin
- CB:
-
conjugated bilirubin (HPLC technique)
- UB:
-
unconjugated bilirubin (HPLC technique)
- % CB:
-
percentage of CB in TB
- DB:
-
direct bilirubin (van den Bergh's method)
- % DB:
-
percentage of DB in TB
- AST:
-
aspartate aminotransferase
- ALP:
-
alkaline phosphatase
- GGT:
-
gamma glutamyltransferase
References
Albert MB, Steinberg WM, Henry JP (1988) Elevated serum levels of tumor marker CA 19-9 in acute cholangitis. Dig Dis Sci 33:1223–1225
Basso D, Fabris C, Del Favero G, Panucci A, Plebani M, Angonese C, Leandro G, Dodi G, Burlina A, Naccarato R (1988) Combined determination of serum CA 19-9 and tissue polypeptide antigen: why no improvement in pancreatic cancer diagnosis? Oncology 45:24–29
Basso D, Fabris C, Meggiato T, Del Favero G, Fogar P, Panozzo MP, Angonese C, Bellinvia S, Munaretto S, Plebani M, Naccarato R (1989) Serum levels of CA 19-9 and tissue polypeptide antigen (TPA) are related to the presence of a benign extra-hepatic cholestasis. Med Sci Res 17:13–14
Basso D, Fabris C, Piccoli A, Plebani M, Del Favero G (1989) Serum tissue polypeptide antigen in pancreatic cancer and other gastrointestinal diseases. J Clin Pathol 42:555
Basso D, Fabris C, Del Favero G, Piccoli A, Angonese C, Pasquali C, Castoro C, Plebani M, Leandro G, Burlina A, Naccarato R (1990) How does liver dysfunction influence serum CA 19-9 in pancreatic cancer? Ital J Gastroenterol 22:1–6
Encabo G, Ruibal A (1986) Seric CA 19-9 levels in patients with non-tumoral pathologies. Our experience in 892 cases. Bull Cancer 73:256–259
Expert Panel for Enzymes/IFCC (1980) Methods for the measurement of catalytic concentrations of enzymes. Part 3. IFCC method for alanine aminotransferase. Clin Chim Acta 105:147F-154F
Expert Panel for Enzymes/IFCC (1983) Methods for the measurement of catalytic concentrations of enzymes. Part 5. IFCC method for alakaline phosphatase. Clin Chem 29:751–761
Hijmans van den Bergh AAH, Snapper I (1913) Dtsch Arch Klin Med 110:540–561
Jalanko H, Kuusela P, Roberts P, Sipponen P, Haglund C, Makelo (1984) Comparison of a new tumor marker, CA 19-9TM, with α-fetoprotein and carcinoembryonic antigen in patients with upper gastrointestinal diseases. J Clin Pathol 37:218–222
Kaplan MM, Kanel GC, Singer JA (1979) Enzyme changes and morphometric analysis of bile ducts in experimental bile duct obstruction. Clin Chim Acta 999:113–119
McFarlane IG (1983) Hepatic clearance of serum glycoproteins. Clin Sci 64:127–135
McNamara E, Goldberg DM (1985) Serum enzymes and enzyme profiles in the diagnosis of liver and biliary tract disease. Surv Dig Dis 3:165–186
Muraca M, Blanckaert N (1983) Liquid chromatographic assay and identification of mono- and diester conjugates of bilirubin in normal serum. Clin Chem 29:1767–1771
Muraca M, Fevery J, Blanckaert N (1987) Relationships between serum bilirubins and production and conjugation of bilirubin. Gastroenterology 92:309–317
Muraca M, Fevery J, Blanckaert N (1988) Analytical aspects and clinical interpretation of serum bilirubins. Semin Liver Dis 8:137–147
Muraca M, Rubaltelli FF, Blanckaert N, Fevery J (1990) Unconjugated and conjugated bilirubin pigments during perinatal development. Biol Neonate 57:1–9
Oelberg DG, Lester R (1986) Cellular mechanism of cholestasis. Ann Rev Med 37:297–317
Paganuzzi M, Onetto M, Marroni P, Barone D, Conio M, Aste H, Pugliese V (1988) CA 19-9 and CA 50 in benign and malignant pancreatic and biliary diseases. Cancer 61:2100–2108
Reichen J, Simon FR (1988) Cholestasis. In: Arias IM, Jakoby WB, Popper H, Schachter D, Shafritz D (eds) The liver: biology and pathobiology. Raven Press, New York, pp 1105–1124
Seetharam S, Sussman N, Komoda T, Alpers DH (1986) The mechanism of elevated alkaline phosphatase activity after bile duct ligation in the rat. Hepatology 6:374–380
Simon FR, Arias IM (1973) Alteration of bile canalicular enzymes in cholestasis. J Clin Invest 52:765–775
Szasz G (1969) A kinetic photometric method for serum gamma glutamyltranspeptidase. Clin Chem 15:124–136
Wulkan RW, Leijnse B (1986) Alkaline phosphatase and cholestasis. Ann Clin Biochem 23:405–412
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Basso, D., Fabris, C., Plebani, M. et al. Alterations in bilirubin metabolism during extra- and intrahepatic cholestasis. Clin Investig 70, 49–54 (1992). https://doi.org/10.1007/BF00422939
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00422939