Biochemical Liver Tests: Recent Developments and Challenges

  • Norbert Blanckaert
Conference paper


Concurrent with the explosive growth of clinical laboratory testing during the last 30 years, an enormous number of biochemical tests have been proposed for diagnosis and monitoring of hepatobiliary disorders. The wealth of candidate tests obviously reflect the myriad of functions performed by the liver. Their development has also been spurred by the intense interest of clinicians who are confronted daily with the question of whether a patient has a hepatobiliary disorder. Notwithstanding this enormous and continuing activity at the drawing boards in hepatological reseach and clinical biochemistry laboratories, almost no change has occurred in the armamentarium of biochemical liver tests routinely employed in clinical practice. Assays of total bilirubin and conjugated bilirubins in serum and bilirubins in urine have been used widely for clinical purposes since the second decade of this century. Measurement of alkaline phosphatase and transaminase activities in serum became widespread in the early 1950s. Together with the one-stage prothrombin time and some form of assessment of serum albumin and gamma-globulins, these analyses continue to be the only biochemical tests to enjoy general acclaim and are considered indispensable clinical tools in the follow-up of patients with suspected or established liver disease.


Alcoholic Liver Disease Hepatocellular Injury Liver Cell Necrosis Hepatobiliary Disorder Pigment Fraction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Acocella G, Tenconi LT, Armas-Merino R, Raia S, Billing BH (1968) Does deconjugation of bilirubin glucuronide occur in obstructive jaundice? Lancet 1: 68–69PubMedCrossRefGoogle Scholar
  2. Aoyagi Y, Isemura M, Suzuki Y, Sekine C, Soga K, Ozaki T, Ichida F (1985) Fucosylated alfa-fetoprotein as marker of early hepatocellular carcinoma. Lancet 1353–1354Google Scholar
  3. Blanckaert N, d’Argenio G (1982) Presence of bilirubins covalently linked to albumin in serum of patients with cholestasis. Gastroenterology 82:1222Google Scholar
  4. Blanckaert N, Servaes R (1983) Formation and excretability in bile of the bilirubin covalently linked to albumin present in serum of rats with conjugated hyperbilirubinemia. Gastroenterology 84: 1364Google Scholar
  5. Blanckaert N, Compernolle F, Leroy P, van Houtte R, Fevery J, Heirwegh KPM (1978) The fate of bilirubin-IXalpha glucuronide in cholestasis and during storage in vitro. Intramolecular rearrangement to positional isomers of glucuronic acid. Biochem J 171: 203–214PubMedGoogle Scholar
  6. Blanckaert N, Gollan JL, Sehmid R (1980a) Mechanism of bilirubin diglucuronide formation in intact rats. J Clin Invest 65:1332–1342PubMedCrossRefGoogle Scholar
  7. Blanckaert N, Kabra PM, Farina FA, Stafford BE, Marton LJ, Schmid R (1980b) Measurement of bilirubin and its monoconjugates and diconjugates in human serum by alkaline methanolysis and high-performance liquid chromatography. J Lab Clin Med 96: 198–212PubMedGoogle Scholar
  8. Blanckaert N, Servaes R, Leroy P (1986) Measurement of bilirubin-protein conjugates in serum and application to human and rat sera. J Lab Clin Med 100: 77–87Google Scholar
  9. Bowers GN Jr, Momb RB (1984) A unifying system for clinical enzymology. Aspartate aminotransferase and the international clinical enzyme scale (ASAT/ICES). Clin Chem 30: 1128–1136PubMedGoogle Scholar
  10. Buamah PK, Cornell C, Casselis-Smith AJ, Harris AL (1986) Fucosylation of alfa-fetoprotein in hepatocellular carcinomas. Lancet 922–923Google Scholar
  11. Christensen E, Schlichting P, Fauerholdt L, Juhl E, Poulsen H, Tygstrup N: Copenhagen Study Group for Liver Diseases (1985) Changes of laboratory variables with time in cirrhosis: prognostic and therapeutic significance. Hepatology 5: 843–853PubMedCrossRefGoogle Scholar
  12. Compernolle F, van Hees GP, Blanckaert N, Heirwegh KPM (1978) Glucuronic acid conjugates of bilirubin-IXalpha glucuronide in cholestasis and during storage in vitro. Intramolecular rearrangement to positional isomers of glucuronic acid. Biochem J 171: 203–214PubMedGoogle Scholar
  13. Eriksen J, Staun Olsen P, Thomsen AaC (1984) Gamma-glutamyltranspeptidase, aspartate aminotransferase, and erythrocyte mean corpuscular volume as indicators of alcohol consumption in liver disease. Scand J Gastroenterol 19: 813–819PubMedGoogle Scholar
  14. Galambos MR, Collins DC, Galambos JT (1985) A radioimmunoassay procedure for type III procollagen: its use in the detection of hepatic fibrosis. Hepatology 5: 38–42PubMedCrossRefGoogle Scholar
  15. Giannoulis E, Arvanitakis C, Nikopoulos A, Doutsos I, Tourkantonis A (1984) Diagnostic value of serum ferritin in primary hepatocellular carcinoma. Digestion 30: 236–241PubMedCrossRefGoogle Scholar
  16. Gluud C, Andersen I, Dietrichson O, Gluud B, Jacobsen A, Juhl E (1981) Gamma-glutamyl-transferase, aspartate aminotransferase and alkaline phosphatase as markers of alcohol consumption in out-patient alcoholics. Eur J Clin Invest 11:171–176PubMedCrossRefGoogle Scholar
  17. Hahn EG (1984) Blood analysis for liver fibrosis. J Hepatol 1: 67–73CrossRefGoogle Scholar
  18. Jenkins WJ, Rosalki SB, Foo Y, et al. (1982) Serum glutamate dehydrogenase is not a good measure of liver cell necrosis in alcoholics. J Clin Pathol 35: 207–210PubMedCrossRefGoogle Scholar
  19. Kobayashi K, Sugimoto T, Makino H, Kumagai M, Unoura M, Tanaka N, Kato Y, Hattori N (1985) Screening methods for early detection of hepatocellular carcinoma. Hepatology 5: 1100–1105PubMedCrossRefGoogle Scholar
  20. Kristenson H, Trell E (1982) Indicators of alcohol consumption. Br J Addict 77: 297–304PubMedCrossRefGoogle Scholar
  21. Lauff JJ, Kaspar MB, Wu T-W, Ambrose RT (1982) Isolation and characterization of a fraction of bilirubin in serum that is firmly bound to protein. Clin Chem 28: 629–637PubMedGoogle Scholar
  22. Lauff JJ, Kasper ME, Ambrose RT (1983) Quantitative liquid-chromatographic estimation of bilirubin species in pathological serum. Clin Chem 29: 800–805PubMedGoogle Scholar
  23. Lesgourgues B, Nalpas B, Berthelot P (1984) Gamma-glutamyltransferase — a simple assay but frequent misinterpretations. Gastroenterol Clin Biol 8: 99–102PubMedGoogle Scholar
  24. Liaw Y-F, Tai D-I, Chu C-M, Lin D-Y, Sheen I-S, Chen T-J, Pao CC (1986) Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis. Gastroenterology 90: 263–267PubMedGoogle Scholar
  25. Liebman HA, Furie BC, Tong MJ, Blanchard RA, Lo K-J, Lee S-D, Coleman MS, Furie B (1984) Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med 310:1427–1731PubMedCrossRefGoogle Scholar
  26. MacNamara E, Goldberg DM (1985) Serum enzymes and enzyme profiles in the diagnosis of liver and biliary tract disease. Surv Dig Dis 3:165–186CrossRefGoogle Scholar
  27. McComb RB, Bowers GN Jr (1985) Alkaline phosphatase and the international clinical enzyme scale. Am J Clin Pathol 84: 67–73PubMedGoogle Scholar
  28. McDonagh AF, Palma LA, Lauff JJ, Wu T-W (1984) Origin of mammalian biliprotein and rearrangement of bilirubin glucuronides in vivo in the rat. J Clin Invest 74: 763–770PubMedCrossRefGoogle Scholar
  29. Miatto O, Casaril M, Gabrielli GB, Nicolo N, Bellisola G, Corrocher R (1985) Diagnostic and prognostic value of serum copper and plasma fibrinogen in hepatic carcinoma. Cancer 55: 774–778PubMedCrossRefGoogle Scholar
  30. Mills PR, Spooner RJ, Russell RI, et al. (1981) Serum glutamate dehydrogenase as a marker of hepatoeyte necrosis in alcoholic liver disease. Br Med J 283: 754–755CrossRefGoogle Scholar
  31. Millward-Sadler GH, Hahn EG, Wright R (1985) Cirrhosis: an appraisal. In: Wright R, MillwardSadler GH, Alberti KGMM, Karran S (eds) Liver and biliary disease, 2nd edn. Bailliere Tindall, Saunders, Eastbourne, pp 821–860Google Scholar
  32. Muraca M, Blanckaert N (1983) Liquid chromatographic assay and identification of mono- and diester conjugates of bilirubin in normal serum. Clin Chem 29:1767–1771PubMedGoogle Scholar
  33. Nakano S, Kumada T, Sugiyama K, Watahiki H, Takeda I (1984) Clinical significance of serum ferritin determination for hepatocellular carcinoma. Am J Gastroenterol 79: 623–627PubMedGoogle Scholar
  34. Nalpas B, Vassault A, Le Guillou A, Lesgourgues B, Ferry N, Lacour B, Berthelot P (1984) Serum activity of mitochondrial aspartate aminotransferase: a sensitive marker of alcoholism with or without alcoholic hepatitis. Hepatology 4: 893–896PubMedCrossRefGoogle Scholar
  35. Orrego H, Kalant H, Israel Y, Blake J, Medline A, Rankin JG, Armstrong A, Kapur B (1979) Effects of short-term therapy with propylthiouracyl in patients with alcoholic liver disease. Gastroenterology 76:105–115PubMedGoogle Scholar
  36. Roberts FD, Sanford NL, Bradbear RA, Cooksley WGE, Powell LW, Halliday JW (1986) Serum procollagen-III-peptide: failure to reflect the extent of hepatic fibrosis. J Gastroenterol Hepatol 1:27–32CrossRefGoogle Scholar
  37. Rohde H, Langer I, Krieg T, Timpl R (1983) Serum and urine analysis of the aminoterminal procollagen peptide type III by radioimmunoassay with antibody Fab fragments. Coll Relat Res 3: 371–379PubMedGoogle Scholar
  38. Rojkind M (1984) The value of serum amino-terminal propeptide of type III procollagen as a marker of liver fibrosis. Hepatology 4: 977–978PubMedCrossRefGoogle Scholar
  39. Ryback RS, Eckardt MJ, Felsher B, Rawlings RR (1982) Biochemical and hematologic correlates of alcoholism and liver disease. JAMA 248: 2261–2265PubMedCrossRefGoogle Scholar
  40. Seligson D, Seligson H, Wu T-W (1985) An anion-exchange chromatographic method for measuring bilirubin covalently bound to albumin. Clin Chem 31:1317–1321PubMedGoogle Scholar
  41. Skinner HA, Holt S, Schuller R, Roy J, Israel Y (1984) Identifikation of alcohol abuse using laboratory tests and a history of trauma. Ann Intern Med 101: 847–851PubMedGoogle Scholar
  42. Vanderlinde RE (1986) Review of pyridoxal phosphate and the transaminase in liver disease. Ann Clin Lab Sci 16: 79–93PubMedGoogle Scholar
  43. Van Waes L, Lieber CS (1977) Glutamate dehydrogenase: a reliable marker of liver cell necrosis in the alcoholic. Br Med J 2:1508–1510PubMedCrossRefGoogle Scholar
  44. Weiss JS, Gautam A, Lauff JJ, Sundberg MW, Jatlow P, Boyer JL, Seligson D (1983) The clinical importance of a protein-bound fraction of serum bilirubin in patients with hyperbilirubinemia. N Engl J Med 309:147–150PubMedCrossRefGoogle Scholar
  45. Worner TM, Lieber CS (1980) Plasma glutamate dehydrogenase, a marker of alcoholic liver injury. Pharmacol Biochem Behav 13: 107–110PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Heidelberg 1987

Authors and Affiliations

  • Norbert Blanckaert
    • 1
  1. 1.Department of Laboratory Medicine and Liver Center, School of MedicineUniversity of CaliforniaSan FranciscoUSA

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