Skip to main content
SpringerLink
Log in

Clinical use of serum enzymes in liver disease

  • Review Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Some of the many enzymes found in hepatocytes can be measured in the serum and are used as tests of liver function. We now review the current knowledge of their physiology and pathophysiology and outline their clinical usefulness. We divide them into two categories: enzymes that primarily reflect cholestasis, such as the alkaline phosphatase, the 5-nucleotidase, and the gamma-glutamyl transpeptidase, and those that primarily reflect hepatocellular necrosis, such as the aminotransferases. We also briefly discuss several enzymes of more limited usefulness.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gutman AB: Serum alkaline phosphatase activity in disease of the skeletal and hepatobiliary systems. Am J Med 27:875–901, 1959

    PubMed  Google Scholar 

  2. Posen S: Alkaline phosphatase. Ann Intern Med 67:183–203, 1967

    PubMed  Google Scholar 

  3. Roberts WM: Variations in the phosphatase activity in the blood in disease. Br J Exp Pathol 11:90–95, 1930

    Google Scholar 

  4. Kaplan MM: Alkaline phosphatase. Gastroenterology 62:452–468, 1972

    PubMed  Google Scholar 

  5. Posen S, Neale FC, Birkett DJ, Brudenell J: Intestinal alkaline phosphatase in human serum. Am J Clin Pathol 48:81–86, 1967

    PubMed  Google Scholar 

  6. Robinson JC, Goldsmith LA: Genetically determined variants of serum alkaline phosphatase: A review. Vox Sang 13:289–307, 1967

    Google Scholar 

  7. Clubb JS, Neale FC, Posen S: The behavior of infused human placental alkaline phosphatase in human subjects. J Lab Clin Med 66:493–507, 1965

    PubMed  Google Scholar 

  8. Clarke LC, Beck E: Plasma “alkaline” phosphatase activity. I. Normative data for growing children. J Pediatr 36:335–341, 1950

    PubMed  Google Scholar 

  9. Kattwinkel J, Taussig LM, Statland BE, Verter JI: The effects of age on alkaline phosphatase and other serologic liver function tests in normal subjects and patients with cystic fibrosis. J Pediatr 82:234–242, 1973

    PubMed  Google Scholar 

  10. Salz JL, Daum F, Cohen MI: Serum alkaline phosphatase activity during adolescence. J Pediatr 82:536–537, 1973

    PubMed  Google Scholar 

  11. Birkett DJ, Done J, Neale FC, Posen S: Serum alkaline phosphatase in pregnancy: An immunologic study. Br Med J 1:1210–1212, 1966

    Google Scholar 

  12. McMaster Y, Tennant R, Clubb JS, Neale FC, Posen S: The mechanism of the elevation of serum alkaline phosphatase in pregnancy. J Obstet Gynaecol Br Emp 71:735–739, 1964

    Google Scholar 

  13. Philip JR, Grodson GM, Carbone JV: Mercaptic conjugation in the uptake and secretion of sulfobromophthalein. Am J Physiol 200:545–547, 1961

    PubMed  Google Scholar 

  14. Klaassen CHL: Age and serum alkaline phosphatase. Lancet 2:1361, 1966

    Google Scholar 

  15. Heino AF, Jokipii SG: Serum alkaline phosphatase levels in the aged. Ann Med Intern Fenn 51:105–109, 1962

    PubMed  Google Scholar 

  16. Deren JJ, Williams LA, Muench H, Chalmers T, Zamcheck N: Comparative study of four methods of determining alkaline phosphatase. N Engl J Med 270:1277–1283, 1964

    PubMed  Google Scholar 

  17. Long CH, Ullrey DE, Miller ER: Serum alkaline phosphatase in the postnatal pig and effect of serum storage on enzyme activity. Proc Soc Exp Biol Med 119:412–414, 1965

    PubMed  Google Scholar 

  18. Wolf PL: Clinical significance of an increased or decreased serum alkaline phosphatase level. Arch Pathol Lab Med 102:497–501, 1978

    PubMed  Google Scholar 

  19. Kaplan MM, Rogers L: Separation of human serum alkaline phosphatase isoenzymes by polyacrylamide gel electrophoresis. Lancet 2:1029–1031, 1969

    PubMed  Google Scholar 

  20. Brensilver HL, Kaplan MM: Significance of elevated liver alkaline phosphatase in serum. Gastroenterology 68:1556–1562, 1975

    PubMed  Google Scholar 

  21. Posen S, Neale FC, Clubb JS: Heat inactivation in the study of human alkaline phosphatase. Ann Intern Med 62:1234–1243, 1965

    PubMed  Google Scholar 

  22. Bahr M, Wilkinson JH: Urea as a selective inhibitor of human tissue alkaline phosphatases. Clin Chim Acta 17:367–370, 1967

    PubMed  Google Scholar 

  23. Kaplan MM: Understanding serum enzyme tests in clinical liver disease.In Problems in Liver Diseases. CS Davidson (ed). New York, Stratton Intercontinental Medical Book, 1979, pp 79–85

    Google Scholar 

  24. Winkelman J, Nadler S, Demetriou J, Pileggi VJ: The clinical usefulness of alkaline phosphatase isoenzyme determinations. Am J Clin Pathol 57:625–634, 1972

    PubMed  Google Scholar 

  25. Connell MD, Dinwoodie AJ: Diagnostic use of serum alkaline phosphatase isoenzymes and 5-nucleotidase. Clin Chim Acta 30:236–241, 1970

    Google Scholar 

  26. Crofton PM: Biochemistry of alkaline phosphatase isoenzymes. CRC Crit Rev Clin Lab Sci 16:161–194, 1982

    Google Scholar 

  27. Kaplan MM: Serum alkaline phosphatase-another piece is added to the puzzle. Hepatology 6:526–528, 1986

    PubMed  Google Scholar 

  28. Chiandussi L: Serum alkaline phosphatase fractions in hepatobiliary and bone disease. Clin Sci 22:425–434, 1962

    PubMed  Google Scholar 

  29. Newton MA: The clinical application of alkaline phosphatase electrophoresis. Q J Med 36:17–28, 1967

    Google Scholar 

  30. Boernig H, et al: Zum Mekanismus der Aktivitaetsanderung der alkalinischen Phosphatase in Leber und Darm der Ratte. Acta Biol Med Ger 22:537, 1969

    PubMed  Google Scholar 

  31. Kaplan MM, Righetti A: Induction of rat liver alkaline phosphatase: The mechanism of the serum elevation in bile duct obstruction. J Clin Invest 49:508–516, 1970

    PubMed  Google Scholar 

  32. Schlaeger R, Haux P, Kattermann R: Studies on the mechanism of the increase in serum alkaline phosphatase activity in cholestasis: Significance of the hepatic bile acid concentration for the leakage of alkaline phosphatase from the rat liver. Enzyme 28:3–13, 1982

    PubMed  Google Scholar 

  33. Kaplan MM, Ohkubo A, Quaroni EG, Sze-Tu D: Increased synthesis of rat liver alkaline phosphatase by bile duct ligation. Hepatology 3:368–376, 1983

    PubMed  Google Scholar 

  34. Righetti ABB, Kaplan MM: Disparate responses of serum and hepatic alkaline phosphatase and 5′-nucleotidase to bile duct obstruction in the rat. Gastroenterology 62:1034–1039, 1972

    PubMed  Google Scholar 

  35. Righetti ABB, Kaplan MM: Effects of actinomycin D on rat liver alkaline phosphatase. Proc Soc Exp Biol Med 136:491–495, 1971

    PubMed  Google Scholar 

  36. Seetharam S, Sussmann NL, Kimoda T, Alpers DM: The mechanism of elevated serum alkaline phosphatase activity after bile duct ligation in the rat. Hepatology 6:374–380, 1986

    PubMed  Google Scholar 

  37. Hatoff DE, Hardison WGM: Induced synthesis of alkaline phosphatase by bile acids in the rat liver cell culture. Gastroenterology 77:1062–1067, 1979

    PubMed  Google Scholar 

  38. Hatoff DE, Hardison WGM: Bile acids modify alkaline phosphatase induction and bile secretion pressure after bile duct obstruction in the rat during cholestasis. Gastroenterology 80:666–672, 1981

    PubMed  Google Scholar 

  39. Kaplan MM, Matloff DS, Selinger MJ, Quaroni EG: Biochemical basis for serum enzyme abnormalities in alcoholic liver disease.In Early Identification of Alcohol Abuse, NIAAA Research Monograph 17. NC Chang, NM Chan (eds). US Dept of Health and Human Services, Rockville, MD, 1985, pp 186–198

    Google Scholar 

  40. Debroe ME, Borgers M, Wieme RJ: The separation and characterization of liver plasma membrane fragments circulating in the blood of patients with cholestasis. Clin Chim Acta 59:369–372, 1975

    PubMed  Google Scholar 

  41. Debroe ME, Roels F, Nouwen EJ, Claeys L, Wieme RJ: Liver plasma membrane: The source of high molecular weight alkaline phosphatase in serum. Hepatology 5:118–128, 1985

    PubMed  Google Scholar 

  42. Hatoff DE, Toyota N, Wong C, Miler AL, Takeya M, Miyai K: Rat liver alkaline phosphatase—evidence that hepatocyte and portal triad enzymes differ. Dig Dis Sci 30:564–572, 1985

    PubMed  Google Scholar 

  43. Seiffert UB, Siede WH, Welsch GJ, Oremek G: Multiple forms of alkaline phosphatases in human liver tissue. Clin Chim Acta 144:17–27, 1984

    PubMed  Google Scholar 

  44. Simon FR, Sutherland E: Hepatic alkaline phosphatase isoenzymes: Isolation, characterization and differential alteration. Enzyme 22:80–90, 1977

    PubMed  Google Scholar 

  45. Komoda T, Kumegawa M, Yajima T, Tamura G, Alpers DH: Induction of rat hepatic and intestinal alkaline phosphatase activity produced by bile from bile duct-ligated animals. Am J Physiol 9:G393-G399, 1984

    Google Scholar 

  46. Perillo RP, Griffin R, Deschryver-Kecskemet K, Lander JJ, Zuckermann JR: Alcoholic liver disease presenting with marked elevation of alkaline phosphatase: A combined clinical and pathological study. Dig Dis Sci 23:1061–1066, 1978

    Google Scholar 

  47. Aisenberg AC, Kaplan MM, Rieder SV, Goldmann JM: Serum alkaline phosphatase at the onset of Hodgkin's disease. Cancer 26:318–326, 1970

    PubMed  Google Scholar 

  48. Utz DC, Warren MM, Gregg JA, Ludwig J: Reversible hepatic dysfunction associated with hypernephroma. Mayo Clin Proc 45:161–169, 1970

    PubMed  Google Scholar 

  49. Fishman WH: Immunologic and biochemical approaches to alkaline phosphatase isoenzyme analysis: The Regan isoenzyme. Ann NY Acad Sci 166:745–759, 1969

    PubMed  Google Scholar 

  50. Wilson JW: Inherited elevation of alkaline phosphatase activity in the absence of disease. N Engl J Med 301:983–984, 1979

    PubMed  Google Scholar 

  51. Goldberg DM: 5-nucleotidase: Recent advances in cell biology, methodology and clinical significance. Digestion 8:87–99, 1973

    PubMed  Google Scholar 

  52. Song CS, Kappas A: 5′-nucleotidase of plasma membranes of the rat liver: Studies on subcellular distribution. Ann NY Acad Sci 166:565–573, 1969

    PubMed  Google Scholar 

  53. Arsenis C, Touster O: Purification and properties of an acid nucleotidase from rat liver lysosomes. J Biol Chem 243:5702–5708, 1968

    PubMed  Google Scholar 

  54. Bailyes FM, Soos M, Jackson P, Newby AC, Sieddle K, Luzio JP: The existence and properties of two dimers of rat liver ecto-5′-nucleotidase. Biochem J 221:369–377, 1984

    PubMed  Google Scholar 

  55. Fritzson P: nucleotidase activities in the soluble fraction of rat liver homogenate. Partial purification and properties of a 5′-nucleotidase with pH optimum 6.3. Biochim Biophys Acta 178:534–541, 1969

    PubMed  Google Scholar 

  56. Chuang NN, Newby AC, Luzio JP: Characterization of different molecular forms of 5′-nucleotidase in normal serum and in serum from cholestatic patients and bile duct ligated rats. Biochem J 224:689–695, 1984

    PubMed  Google Scholar 

  57. Helfield A, Goldberg A: Normal ranges and diagnostic value of serum hb5′-nucleotidase and alkaline phosphatase activities in infancy. Arch Dis Child 46:842–846, 1971

    PubMed  Google Scholar 

  58. Hardawill C, Chang G: Serum lactic dehydrogenase, leucine aminopeptidase and 5′-nucleotidase activities: Observations in patients with carcinoma of the pancreas and hepatobiliary disease. Can Med Assoc J 89:755–761, 1963

    PubMed  Google Scholar 

  59. Hill PG, Sammons HG: An assessment of 5′-nucleotidase as a liver function test. Q J Med 36:457–468, 1967

    PubMed  Google Scholar 

  60. Kowlessar OD, Haeffner IJ, Riley EM, Sleisenger MH: Comparative study of serum leucine aminopeptidase, 5′-nucleotidase and nonspecific alkaline phosphatase in diseases affecting the pancreas, hepatobiliary tree and bone. Am J Med 31:231–237, 1961

    PubMed  Google Scholar 

  61. Young II: Serum 5′-nucleotidase: Characterization and evaluation in disease states. Ann NY Acad Sci 75:357–362, 1958

    PubMed  Google Scholar 

  62. Fritzson P: Dephosphorylation of pyrimidine nucleotides in the soluble fraction of homogenates from normal and regenerating rat liver. Eur J Biochem 1:12–20, 1967

    Google Scholar 

  63. Campbell DM: Determination of 5′-nucleotidase in blood serum. Biochem J 82:34P, 1962

  64. Belfield A, Ellis G, Goldberg DM: A specific colorimetric 5′-nucleotidase assay utilizing the Berthelot reaction. Clin Chem 16:396–401, 1970

    PubMed  Google Scholar 

  65. Price CP, Hill PG, Sammons HG: A comparison of two colorimetric procedures for the assay of 5′-nucleotidase. Clin Chim Acta 33:260–263, 1971

    PubMed  Google Scholar 

  66. Belfield A, Goldberg DM: Inhibition of the nucleotidase effect of alkaline phosphatase by beta-glycerophosphate. Nature 219:73–75, 1968

    PubMed  Google Scholar 

  67. Kaplan MM, Kanel GC, Singer JA: Enzyme changes and morphometric analysis of bile ducts in experimental bile duct obstruction. Clin Chim Acta 99:113–119, 1979

    PubMed  Google Scholar 

  68. Schenker S, Balint J, Schiff L: Differential diagnosis of jaundice: report of a prospective study of 61 proved cases. Am J Dig Dis 7:449–463, 1962

    Google Scholar 

  69. Ellis G, Goldberg D, Spooner FM: Serum enzyme tests in diseases of the liver and biliary tree. Am J Clin Pathol 70:248–258, 1978

    PubMed  Google Scholar 

  70. Vinnik IE, Kern F, Corley WD: Serum 5′-nucleotidase and pericholangitis in patients with chronic ulcerative colitis. Gastroenterology 45:492–498, 1963

    PubMed  Google Scholar 

  71. Eshchar J, Rudzki C, Zimmerman HJ: Serum levels of 5′-nucleotidase in disease. Am J Clin Pathol 47:598–606, 1967

    PubMed  Google Scholar 

  72. Kim NK, Yasmineh WG, Freier EF, Goldman AI, Theologides A: Value of alkaline phosphatase, 5′-nucleotidase, gamma-glutamyl transferase and glutamate dehydrogenase activity measurements (single and combined) in serum diagnosis of metastases to the liver. Clin Chem 23:2034–2038, 1977

    PubMed  Google Scholar 

  73. Seitanidis B, Moss DW: Serum alkaline phosphatase and 5′-nucleotidase levels during normal pregnancy. Clin Chim Acta 25:183–184, 1969

    PubMed  Google Scholar 

  74. Kater RMH, Mistilis SP: Obstetric cholestasis and pruritus of pregnancy. Med J Aust 54:638–642, 1967

    Google Scholar 

  75. Kreek MJ: Cholestasis of pregnancy and during ethinyl estradiol administration in the human and rat.In Metabolic Effect of Gonadal Hormones and Contraceptive Steroids. HA Salahnick, DM Kipnis, RLVande Wiele (eds). New York, Plenum Press, 1969, pp 40–58

    Google Scholar 

  76. Goldberg DM: Structural, functional and clinical aspects of gamma-glutamyl transferase. CRC Crit Rev Clin Lab Sci 12:1–58, 1980

    PubMed  Google Scholar 

  77. Meier PJ, Sztul ES, Reuben A, Boyer JL: Structural and functional polarity of canalicular and basolateral plasma membrane vesicles isolated in high yield from rat liver. J Cell Biol 98:991–1000, 1984

    PubMed  Google Scholar 

  78. Wenham PR, Horn DB, Smith AF: Multiple forms of gamma-glutamyl transferase: A clinical study. Clin Chem 31:569–573, 1985

    PubMed  Google Scholar 

  79. Zimmerman HJ: Evaluation of the function and integrity of the liver.In Clinical Diagnosis and Management by Laboratory Methods. JB Henry (ed). 1979, pp 305–346

  80. Lum G, Gambino SR: Serum gamma-glutamyl transpeptidase activity as an indicator of disease of the liver, pancreas and bone. Clin Chem 18:358–362, 1972

    PubMed  Google Scholar 

  81. Sczeklik E, Orlowski M, Szewczuk A: Serum gammaglutamyl transpeptidase activity in liver disease. Gastroenterology 41:353–359, 1961

    Google Scholar 

  82. Zein M, Discombe G: Serum gamma-glutamyl transpeptidase activity as a diagnostic aid. Lancet 2:748–750, 1970

    PubMed  Google Scholar 

  83. Meister A: The gamma-glutamyl cycle. Diseases associated with specific enzyme deficiencies. Ann Intern Med 81:247–253, 1974

    PubMed  Google Scholar 

  84. Meister A: Gluthathione and the gamma-glutamyl cycle.In Glutathione: Metabolism and Function. IM Arias, WB Jakoby (eds). New York, Raven Press, 1976, p 35

    Google Scholar 

  85. Meister A, Tate SS: Glutathione and related gamma-glutamyl compounds: Biosynthesis and utilization. Annu Rev Biochem 45:559–604, 1976

    PubMed  Google Scholar 

  86. Shaw LM, Neuman DA: Hydrolysis of glutathione by human liver gamma-glutamyl transferase. Clin Chem 25:75–79, 1979

    PubMed  Google Scholar 

  87. Szasz G: A kinetic photometric method for serum gammaglutamyl transpeptidase. Clin Chem 15:124–136, 1969

    PubMed  Google Scholar 

  88. Szasz G: Reaction rate method for gamma-glutamyl transferase activity in serum. Clin Chem 22:2051–2055, 1976

    PubMed  Google Scholar 

  89. Rosalki SB, Tarlow D, Rau D: Plasma gamma glutamyl transpeptidase elevation in patients receiving enzyme inducing drugs. Lancet 2:376–377, 1971

    Google Scholar 

  90. Singh HP, Hebert MA, Gault MH: Effects of some drugs on clinical laboratory values as determined by the technicon SMA 12/60. Clin Chem 18:137–144, 1972

    PubMed  Google Scholar 

  91. Whitfield JB, Pounder RE, Neale G, Moss DW: Serum gamma-glutamyl tidase activity in liver disease. Gut 13:702–708, 1972

    PubMed  Google Scholar 

  92. Whitfield JB, Moss DW, Neale J, Orme M, Breckenridge A: Changes in gamma-glutamyl transferase activity associated with alterations in drug metabolism in man. Br Med J 1:316–318, 1973

    PubMed  Google Scholar 

  93. Harouki R, Chobert MN, Finidori J, Aggerbeck M, Nalpas B, Hanoune J: Ethanol effects in a rat hepatoma cell line: Induction of gamma-glutamyl transferase. Hepatology 3:323–329, 1983

    PubMed  Google Scholar 

  94. Lamy J, Bagliss MC, Ferrant JP, Weill J: Determination de la gamma-glutamyl transpeptidase des ethyliques a la suite du sevrage. Clin Chim Acta 56:169–173, 1974

    PubMed  Google Scholar 

  95. Rollason JG, Pinkerle G, Robinson D: Serum gammaglutamyl transpeptidase in relation to alcohol consumption. Clin Chim Acta 39:75–80, 1972

    PubMed  Google Scholar 

  96. Rosalki S, Rau D: Serum gamma-glutamyl transpeptidase activity in alcoholism. Clin Chim Acta 39:41–47, 1972

    PubMed  Google Scholar 

  97. Westwood M, Cohen MI, McNamara H: Serum gammaglutamyl transpeptidase activity: A chemical determinant of alcohol consumption during adolescence. Pediatrics 62:560–562, 1978

    PubMed  Google Scholar 

  98. Whitehead TP, Clarke CA, Whitfield AGW: Biochemical and haematological markers of alcohol intake. Lancet 1:978–981, 1978

    PubMed  Google Scholar 

  99. Ivanov E, Adjarov D, Etarska M, Stankushev T, Brum barov K, Kerimova M: Elevated liver gamma-glutamyl transferase in chronic alcoholics. Enzyme 25:304–308, 1980

    PubMed  Google Scholar 

  100. Selinger MJ, Matloff DS, Kaplan MM: Gamma-glutamyl transpeptidase activity in liver disease: Serum elevation is independent of hepatic GGTP activity. Clin Chim Acta 125:283–290, 1982

    PubMed  Google Scholar 

  101. Huseby NE, Torstein V: The activity of gamma-glutamyl transferase after bile duct ligation in guinea pig. Clin Chim Acta 88:385–392, 1978

    PubMed  Google Scholar 

  102. Betro MG, Oon RCS, Edwards JB: Gamma-glutamyl transpeptidase in diseases of the liver and bone. Am J Clin Pathol 60:672–678, 1973

    PubMed  Google Scholar 

  103. Ideo G, Morganti A, Dioguardi N: Gamma-glutamyl transpeptidase: A clinical and experimental study. Digestion 5:326–336, 1972

    PubMed  Google Scholar 

  104. Rutenburg AM, Goldbarg JA, Pineda EP: Serum gammaglutamyl transpeptidase activity in hepatobiliary and pancreatic disease. Gastroenterology 45:43–48, 1963

    PubMed  Google Scholar 

  105. Walker FB, Hobbit DL, Cunningham FG, Combes B: Gamma-glutamyl transpeptidase in normal pregnancy. Obstet Gynecol 43:745–749, 1974

    PubMed  Google Scholar 

  106. Burrows S, Feldman W, McBride F: Serum gamma-glutamyl transpeptidase: Evaluation in screening of hospitalized patients. Am J Clin Pathol 64:311–314, 1975

    PubMed  Google Scholar 

  107. Combes B, Shore GM, Cunningham FG, Walker FB, Shorey JW, Ware A: Serum gamma-glutamyl transpeptidase activity in viral hepatitis: Suppression in pregnancy and by birth control pills. Gastroenterology 72:271–274, 1977

    PubMed  Google Scholar 

  108. Rutenburg AM, Goldbarg JA, Pineda EP: Leucine aminopeptidase activity: Observations in patients with cancer of the pancreas and other diseases. N Engl J Med 259:469–472, 1958

    PubMed  Google Scholar 

  109. Kowlessar OD, Haeffner IJ, Sleisenger MH: Localization of leucine aminopeptidase in serum and body fluids by starch gel electrophoresis. Am J Med 31:231–237, 1961

    PubMed  Google Scholar 

  110. Banks BM, Pineda EP, Goldbarg JA, Rutenburg AM: Clinical value of serum leucine aminopeptidase determinations. N Engl J Med 263:1277–1281, 1960

    PubMed  Google Scholar 

  111. Pruzanski W, Fischl J: The evaluation of serum leucine aminopeptidase estimation: The influence of the administration of steroids on S-LAP activity in obstructive disease of the biliary tract (preliminary report). Am J Med Sci 248:581–587, 1964

    PubMed  Google Scholar 

  112. Bressler R, Forsyth BR: Serum leucine aminopeptidase activity in normal pregnancy and in patients with hydatidiform mole. N Engl J Med 261:746–748, 1959

    PubMed  Google Scholar 

  113. Rutenburg AM, Banks BM, Pineda EP, Goldbarg JA: A comparison of serum aminopeptidase and alkaline phosphatase in the detection of hepatobiliary disease in anicteric patients. Ann Intern Med 61:50–55, 1964

    PubMed  Google Scholar 

  114. Rutenburg AM, Pineda EP, Goldberg JA, Levitan R, Gellis SS, Silverberg M: Serum leucine aminopeptidase activity: In normal infants, in biliary atresia and in other diseases. Am J Dis Child 103:47–54, 1962

    PubMed  Google Scholar 

  115. Bressler R, Forsyth BR, Klatskin G: Serum leucine aminopeptidase activity in hepatobiliary and pancreatic disease. J Lab Clin Med 56:417–430, 1960

    Google Scholar 

  116. De Ritis F, Giusti G, Piccinino F, Cacciatore L: Biochemical lab tests in viral hepatitis and other hepatic diseases. Bull WHO 32:59–72, 1965

    PubMed  Google Scholar 

  117. Wrobleski F: The clinical significance of transaminase activities in serum. Am J Med 27:911–923, 1959

    PubMed  Google Scholar 

  118. Zimmerman HJ, West M: Serum enzyme levels in the diagnosis of hepatic disease. Am J Gastroenterol 40:387–404, 1963

    PubMed  Google Scholar 

  119. Diehl AM, Potter J, Boitnott J, Van Duyn MA, Herlong HF, Mezey E: Relationship between pyridoxal 5′-phosphate deficiency and aminotransferase levels in alcoholic hepatitis. Gastroenterology 86:632–636, 1984

    PubMed  Google Scholar 

  120. Rej R: Aspartate aminotransferase activity and isoenzyme proportion in human liver tissues. Clin Chem 24:1971–1979, 1978

    PubMed  Google Scholar 

  121. Boyde TRC, Latner AL: Starch gel electrophoresis of transaminases in human tissue extracts and serum. Biochem J 82:51P, 1962

    Google Scholar 

  122. Morino Y, Kagamiyama H, Wada H: Immunochemical distinction of glutamic oxaloacetic transaminases from soluble and mitochondrial fractions of mammalian tissues. J Biol Chem 239:943–944, 1964

    PubMed  Google Scholar 

  123. Rej R: Measurement of aminotransferase; Part 1: Aspartate aminotransferase. CRC Crit Rev Clin Lab Sci 21:99–186, 1985

    Google Scholar 

  124. Kamimoto Y, Horiuchi S, Tanase S, Morino Y: Plasma clearance of intravenously injected aspartate aminotransferase isozymes: Evidence for preferential uptake by sinusoidal liver cells. Hepatology 5:367–375, 1985

    PubMed  Google Scholar 

  125. Dunn M, Martins J, Reissmann KR: The disappearance rate of glutamic oxaloacetic transaminase from the circulation and its distribution in the body fluid compartments and secretions. J Lab Clin Med 51:259–265, 1958

    PubMed  Google Scholar 

  126. Frankl HD, Merritt JH: Enzyme activity in the serum and common duct bile of dogs. Am J Gastroenterol 31:166–170, 1959

    PubMed  Google Scholar 

  127. De Ritis F, Coltorti M, Giusti G: Transaminase activity in liver disease. Lancet 2:214–215, 1958

    Google Scholar 

  128. Clermont RJ, Chalmers TC: The transaminase tests in liver disease. Medicine 46:197–207, 1967

    PubMed  Google Scholar 

  129. Matloff DS, Selinger MJ, Kaplan MM: Hepatic transaminase activity in alcoholic liver disease. Gastroenterology 78:1389–1392, 1980

    PubMed  Google Scholar 

  130. Cohen JA, Kaplan MM: The SGOT/SGPT ratio-an indicator of alcoholic liver disease. Dig Dis Sci 24:835–838, 1979

    PubMed  Google Scholar 

  131. Abbruzzese A, Jeffrey RL: Marked elevation of serum glutamic oxaloacetic transaminase and lactic dehydrogenase activity in chronic extrahepatic biliary disease. Am J Dig Dis 14:332–338, 1969

    PubMed  Google Scholar 

  132. Dreyfus JC, Schapira G, Schapira F: Serum enzymes in the physiopathology of muscle. Ann NY Acad Sci 75:235–249, 1959

    Google Scholar 

  133. De Ritis F, Coltorti M, Giusti G: Serum transaminase activities in liver disease. Lancet 1:685–687, 1972

    Google Scholar 

  134. Gerety RJ (ed): Non-A, Non-B Hepatitis. New York, Academic Press, 1981

    Google Scholar 

  135. Soloway RD, Summerskill WHJ, Baggenstoss AH, Geall MG, Gitnick GL, Elveback LR, Schoenfied LJ: Clinical, biochemical and histological remission of severe chronic active liver disease: A controlled study of treatments and early prognosis. Gastroenterology 63:820–833, 1972

    PubMed  Google Scholar 

  136. Franklin M, Bean WB, Paul WD, Routh JI, Huerga JDL, Popper H: Electrophoretic studies in liver disease. II. Gammaglobulin in chronic liver disease. J Clin Invest 30:729–737, 1951

    PubMed  Google Scholar 

  137. Sabath LD, Gerstein DA, Finland M: Serum glutamic oxaloacetic transaminase. False elevation during administration of erythromycin. N Engl J Med 279:1137–1139, 1968

    PubMed  Google Scholar 

  138. Young DS, Thomas DW, Friedman RD, Pestaner LI: Effects of drugs on clinical lab tests. Clin Chem 18:1041–1042, 1972

    PubMed  Google Scholar 

  139. Warnock LG, Stone WJ, Wagner L: Decreased aspartate aminotransferase (“SGOT”) activity in serum of uremic patients. Clin Chem 20:1213–1216, 1974

    PubMed  Google Scholar 

  140. Panteghini M, Falsetti F, Chiari E, Malchiodi A: Determination of aspartate isoenzymes in hepatic diseases—preliminary findings. Clin Chim Acta 128:133–140, 1983

    PubMed  Google Scholar 

  141. Nalpas B, Varsault A, Le Guillou A, Lacour B, Berthelot P: A new marker of chronic alcoholism: Serum mitochondrial aspartate amino-transferase.In Early Identification of Alcohol Abuse, NIAAA Research Monograph 17. NC Chang, NM Chan (eds). US Dept of Health and Human Services, Rockville, MD, 1985, pp 94–99

    Google Scholar 

  142. Nalpas B, Vassault A, Charpin S, Lacour B, Berthelot P: Serum mitochondrial aspartate aminotransferase as a marker of chronic alcoholism: Diagnostic value and interpretation in a liver unit. Hepatology 6:608–614, 1986

    PubMed  Google Scholar 

  143. Nishimura T, Yoshida Y, Watanabe F, Koseki M, Nishida T, Tagawa K, Kawashima Y: Blood level of mitochondrial aspartate aminotransferase as an indicator of the extent of ischemic necrosis of the rat liver. Hepatology 6:701–707, 1986

    PubMed  Google Scholar 

  144. Remmer AR Jr, Kaljot V: Serum transaminase levels. Effects of strenuous and prolonged physical exercise on healthy young subjects. JAMA 185:968–970, 1963

    PubMed  Google Scholar 

  145. Wolf PL: Lactate dehydrogenase-6: A biochemical sign of serious hepatic circulatory disturbance. Arch Intern Med 145:1396–1397, 1985

    PubMed  Google Scholar 

  146. Rosalki SB: Enzyme tests in diseases of the liver and hepatobiliary tract.In The Principles and Practice of Diagnostic Enzymology. JH Wilkinson (ed). London, Edward Arnold, 1973, pp 303–360

    Google Scholar 

  147. Schmidt F, Schmidt FW: Methode und Wert der Bestimmung der Glutaminsaure-Dehydrogenawe Aktivitaet in Serum. Klin Wochenschr 40:962–969, 1962

    PubMed  Google Scholar 

  148. Okumura M, Spellberg MA: Serum isocitric dehydrogenase activity in the differential diagnosis of liver disease. Gastroenterology 39:305–311, 1960

    PubMed  Google Scholar 

  149. Sterkel RL, Spencer JA, Wolfson SK, Williams-Ashman HG: Serum isocitric dehydrogenase activity with particular reference to liver disease. J Lab Clin Med 52:176–184, 1958

    PubMed  Google Scholar 

  150. West M, Schwartz MA, Cohen J, Zimmerman HJ: Glycolytic and oxidative enzymes and transaminases in patients with carcinoma of the kidney, prostate and urinary bladder. Cancer 17:432–437, 1964

    PubMed  Google Scholar 

  151. Guder WG, Habicht A, Kleissl J, Schmidt U, Witland OH: The diagnostic significance of liver cell inhomogeneity: Serum enzymes in patients with central liver necrosis and the distribution of glutamic dehydrogenase in normal human liver. Z Klin Chem Klin Biochem 13:311–318, 1975

    PubMed  Google Scholar 

  152. Svoboda DJ, Manning RT: Chronic alcoholism with metamorphosis of the liver. Mitochondrial alterations in hepatic cells. Am J Pathol 44:645–652, 1964

    PubMed  Google Scholar 

  153. Van Waes, Lieber CS: Glutamate dehydrogenase: A reliable marker of liver cell necrosis in the alcoholic. Br Med J 2:1508–1510, 1977

    PubMed  Google Scholar 

  154. Jenkins WJ, Rosalki SB, Foo Y, Scheuer PJ, Nemsanszky E, Sherlock S: Serum glutamate dehydrogenase is not a reliable marker of liver cell necrosis in alcoholics. J Clin Pathol 35:207–210, 1982

    PubMed  Google Scholar 

  155. Jung K, Pergandi M, Rej R, Schreiber G, Schimmelpfennig W: Mitochondrial enzymes in human serum: comparative determinations of glutamate dehydrogenase and mitochondrial aspartate aminotransferase in healthy persons and patients with chronic liver diseases. Clin Chem 31:239–243, 1985

    PubMed  Google Scholar 

  156. Mills PR, Spooner RJ, Russell RI, Boyle P, MacSween RNM: Serum glutamate dehydrogenase as a marker of hepatocyte necrosis in alcoholic liver disease. Br Med J 283:754–755, 1981

    Google Scholar 

  157. Reichard H: Ornithine carbamyl transferase activity in human serum in diseases of the liver and biliary system. J Lab Clin Med 57:78–87, 1961

    PubMed  Google Scholar 

  158. Konttinen A: Multiple serum enzyme analysis in chronic alcoholics. Acta Med Scand 188:257–264, 1970

    PubMed  Google Scholar 

  159. Deshmuk DH, Rittenhouse JW, Mason M, Baublis JW: Serum ornithine carbamyl transferase activities in Reye's syndrome. Enzyme 27:45–51, 1982

    PubMed  Google Scholar 

  160. Deshmuk DH, Thomas PE, McArthur B, Sarnaik AP: Serum glutamate dehydrogenase and ornithine carbamyl transferase in Reye's syndrome. Enzyme 33:171–174, 1985

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gastroenterology Division, Department of Medicine, New England Medical Center, 750 Washington Street, 02111, Boston, Massachusetts

    Jacques J. Reichling MD & Marshall M. Kaplan MD

Authors
  1. Jacques J. Reichling MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marshall M. Kaplan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reichling, J.J., Kaplan, M.M. Clinical use of serum enzymes in liver disease. Digest Dis Sci 33, 1601–1614 (1988). https://doi.org/10.1007/BF01535953

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01535953

Key words

Search

Navigation