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Assessment of Liver Function in Clinical Practice

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Chronic Liver Failure

Part of the book series: Clinical Gastroenterology ((CG))

Abstract

A broad array of biochemical tests are used to assess the various functions of the liver and evaluate patients with suspected or established liver disease. These tests are collectively referred to as “liver function tests,” a term that is often criticized because the most commonly used tests—the aminotransferases and alkaline phosphatase—are not true measures of liver synthetic, excretory, or metabolic function (1). Rather, these values normally indicate hepatocyte damage or liver inflammation or infiltration.

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References

  1. Aranda-Michel J, Sherman KE. Tests of the liver: use and misuse. Gastroenterologist 1998;6:34–43.

    PubMed  CAS  Google Scholar 

  2. Karmen A, Wroblewski F, Ladue JS. Transaminase activity in human blood. J Clin Invest 1955;34:126–31.

    Article  PubMed  CAS  Google Scholar 

  3. Rej R. Aspartate aminotransferase activity and isoenzyme proportions in human liver tissues. Clin Chem 1978;24:1971–9.

    PubMed  CAS  Google Scholar 

  4. Kallai L, Hahn A, Roeder V, et al. Correlation between histological findings and serum transaminase values in chronic diseases of the liver. Acta Med Scand 1964;175:49–56.

    Article  PubMed  CAS  Google Scholar 

  5. Kaplan MM. Alanine aminotransferase levels: what's normal? Ann Intern Med 2002;137:49–51.

    PubMed  Google Scholar 

  6. Kim HC, Nam CM, Jee SH, et al. Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study. BMJ 2004;328:983.

    Article  PubMed  CAS  Google Scholar 

  7. Piton A, Poynard T, Imbert-Bismut F, et al. Factors associated with serum alanine transaminase activity in healthy subjects: consequences for the definition of normal values, for selection of blood donors, and for patients with chronic hepatitis C. MULTIVIRC Group. Hepatology 1998;27:1213–9.

    Article  PubMed  CAS  Google Scholar 

  8. Prati D, Taioli E, Zanella A, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 2002;137:1–10.

    PubMed  CAS  Google Scholar 

  9. Kechagias S, Ernersson A, Dahlqvist O, et al. Fast Food Study Group. Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects. Gut 2008;57:649–54.

    Article  PubMed  CAS  Google Scholar 

  10. Watkins PB, Kaplowitz N, Slattery JT, et al. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA 2006;296:87–93.

    Article  PubMed  CAS  Google Scholar 

  11. Klatsky AL, Morton C, Udaltsova N, et al. Coffee, cirrhosis, and transaminase enzymes. Arch Intern Med 2006;166:1190–5.

    Article  PubMed  Google Scholar 

  12. Ruhl CE, Everhart JE. Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology 2009;36:477–85.

    Article  CAS  Google Scholar 

  13. Fishman WH. Perspectives on alkaline phosphatase isoenzymes. Am J Med 1974;56:617–50.

    Article  PubMed  CAS  Google Scholar 

  14. Goldfischer S, Essner E, Novikoff AB. The localization of phosphatase activities at the level of ultrastructure. J Histochem Cytochem 1964;12:72–95.

    PubMed  CAS  Google Scholar 

  15. Hulstaert CE, Torringa JL, Koudstaal J, et al. The characteristic distribution of alkaline phosphatase in the full-term human placenta. An electron cytochemical study. Gynecol Invest 1973;4:23–30.

    Article  PubMed  CAS  Google Scholar 

  16. Bates JM, Akerlund J, Mittge E, et al. Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. Cell Host Microbe 2007;2:371–82.

    Article  PubMed  CAS  Google Scholar 

  17. Kaplan MM. Serum alkaline phosphatase—another piece is added to the puzzle. Hepatology 1986;6:526–8.

    Article  PubMed  CAS  Google Scholar 

  18. Stolbach LL, Krant MJ, Inglis NI, et al. Correlation of serum L-phenylalanine-sensitive alkaline phosphatase, derived from intestine, with the ABO blood group of cirrhotics. Gastroenterology 1967;52:819–27.

    PubMed  CAS  Google Scholar 

  19. Bacq Y, Zarka O, Brechot JF, et al. Liver function tests in normal pregnancy: a prospective study of 103 pregnant women and 103 matched controls. Hepatology 1996;23:1030–4.

    Article  PubMed  CAS  Google Scholar 

  20. Birkett DJ, Done J, Neale FC, et al. Serum alkaline phosphatase in pregnancy; an immunological study. Br Med J 1966;1:1210–2.

    Article  PubMed  CAS  Google Scholar 

  21. Gordon T. Factors associated with serum alkaline phosphatase level. Arch Pathol Lab Med 1993;117:187–90.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  23. Rutenberg AM, Goldberg JA, Pineda GP, et al. Serum γ-glutamyl transpeptidase activity in hepatobiliary pancreatic disease. Gastroenterology 1963;45:43–8.

    Google Scholar 

  24. Rosalki SB, Tarlow D, Rau D. Plasma gamma-glutamyl transpeptidase elevation in patients receiving enzyme-inducing drugs. Lancet 1971;2:376–7.

    Article  PubMed  CAS  Google Scholar 

  25. Goldberg DM. 5' Nucleotidase: recent advances in cell biology, methodology and clinical significance. Digestion 1973;8:87–99.

    Article  PubMed  CAS  Google Scholar 

  26. Poland RL, Odell GB. Physiologic jaundice: the enterohepatic circulation of bilirubin. N Engl J Med 1971;284:1–6.

    Article  PubMed  CAS  Google Scholar 

  27. Bosma PJ, Seppen J, Goldhoorn B, et al. Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. J Biol Chem 1994;269:17960–4.

    PubMed  CAS  Google Scholar 

  28. van den Bergh AA MP. Uber eine direkte und eine indirekte Diazoreaktion auf Bilirubin. Biochem Z 1916:90.

    Google Scholar 

  29. Schalm L, Schulte MJ. The quantitative determination of the two types of bilirubin simultaneously present in the blood, and its clinical importance. Am J Med Sci 1950;219:606–16.

    Article  PubMed  CAS  Google Scholar 

  30. Giannini E, Botta F, Fasoli A, et al. Progressive liver functional impairment is associated with an increase in AST/ALT ratio. Dig Dis Sci 1999;44:1249–53.

    Article  PubMed  CAS  Google Scholar 

  31. Shaheen AA, Myers RP. Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis C-related fibrosis: a systematic review. Hepatology 2007;46:912–21.

    Article  PubMed  Google Scholar 

  32. Lok AS, Ghany MG, Goodman ZD, et al. Predicting cirrhosis in patients with hepatitis C based on standard laboratory tests: results of the HALT-C cohort. Hepatology 2005;42:282–92.

    Article  PubMed  Google Scholar 

  33. Fujii H, Enomoto M, Fukushima W, et al. Noninvasive laboratory tests proposed for predicting cirrhosis in patients with chronic hepatitis C are also useful in patients with non-alcoholic steatohepatitis. J Gastroenterol 2009;44:608–14.

    Article  PubMed  Google Scholar 

  34. Diehl AM, Potter J, Boitnott J, et al. Relationship between pyridoxal 5'-phosphate deficiency and aminotransferase levels in alcoholic hepatitis. Gastroenterology 1984;86:632–6.

    PubMed  CAS  Google Scholar 

  35. Firth JD, Ebert BL, Pugh CW, et al. Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3' enhancer. Proc Natl Acad Sci U S A 1994;91:6496–500.

    Article  PubMed  CAS  Google Scholar 

  36. Fuchs S, Bogomolski-Yahalom V, Paltiel O, et al. Ischemic hepatitis: clinical and laboratory observations of 34 patients. J Clin Gastroenterol 1998;26:183–6.

    Article  PubMed  CAS  Google Scholar 

  37. Cassidy WM, Reynolds TB. Serum lactic dehydrogenase in the differential diagnosis of acute hepatocellular injury. J Clin Gastroenterol 1994;19:118–21.

    Article  PubMed  CAS  Google Scholar 

  38. Kotoh K, Enjoji M, Kato M, et al. A new parameter using serum lactate dehydrogenase and alanine aminotransferase level is useful for predicting the prognosis of patients at an early stage of acute liver injury: a retrospective study. Comp Hepatol 2008;7:6.

    Article  PubMed  CAS  Google Scholar 

  39. Daniel S, Ben-Menachem T, Vasudevan G, et al. Prospective evaluation of unexplained chronic liver transaminase abnormalities in asymptomatic and symptomatic patients. Am J Gastroenterol 1999;94:3010–4.

    Article  PubMed  CAS  Google Scholar 

  40. Mayo MJ. Primary biliary cirrhosis: the future. Clin Liver Dis 2003;7:957–69.

    Article  PubMed  Google Scholar 

  41. Matheus T, Munoz S. Granulomatous liver disease and cholestasis. Clin Liver Dis 2004;8:229–46.

    Article  PubMed  Google Scholar 

  42. Maldonado O, Demasi R, Maldonado Y, et al. Extremely high levels of alkaline phosphatase in hospitalized patients. J Clin Gastroenterol 1998;27:342–5.

    Article  PubMed  CAS  Google Scholar 

  43. Harris MJ, Le Couteur DG, Arias IM. Progressive familial intrahepatic cholestasis: genetic disorders of biliary transporters. J Gastroenterol Hepatol 2005;20:807–17.

    Article  PubMed  CAS  Google Scholar 

  44. Tarantino G, Di Minno MN, Capone D. Drug-induced liver injury: is it somehow foreseeable? World J Gastroenterol 2009;15:2817–33.

    Article  PubMed  CAS  Google Scholar 

  45. Benichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol 1990;11:272–6.

    Article  PubMed  CAS  Google Scholar 

  46. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239–45.

    Article  PubMed  CAS  Google Scholar 

  47. Danan G, Benichou C. Causality assessment of adverse reactions to drugs–I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol 1993;46:1323–30.

    Article  PubMed  CAS  Google Scholar 

  48. Usui K, Oda Y, Kubota R, et al. Clinical application of the leukocyte migration test and new diagnostic criteria for identifying causative agents in patients with drug-induced liver injury. Hepatogastroenterology 2007;54:1752–7.

    PubMed  Google Scholar 

  49. Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol 2008;14:6774–85.

    Article  PubMed  Google Scholar 

  50. Reuben A. Hyʹs law. Hepatology 2004;39:574–8.

    Article  PubMed  Google Scholar 

  51. Bjornsson E, Olsson R. Suspected drug-induced liver fatalities reported to the WHO database. Dig Liver Dis 2006;38:33–8.

    Article  PubMed  CAS  Google Scholar 

  52. Andrade RJ, Lucena MI, Fernandez MC, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology 2005;129:512–21.

    PubMed  Google Scholar 

  53. Tripodi A, Chantarangkul V, Primignani M, et al. The international normalized ratio calibrated for cirrhosis (INR(liver)) normalizes prothrombin time results for model for end-stage liver disease calculation. Hepatology 2007;46:520–7.

    Article  PubMed  Google Scholar 

  54. Bellest L, Eschwege V, Poupon R, et al. A modified international normalized ratio as an effective way of prothrombin time standardization in hepatology. Hepatology 2007;46:528–34.

    Article  PubMed  Google Scholar 

  55. Lord JW, Andrus W. Differentiation of intrahepatic and extrahepatic jaundice. Response of the plasma prothrombin to intramuscular injemction of menadione (2-methyl-1, 4-naphthoquinone) as a diagnostic aid. Arch Intern Med 1941;68:199.

    CAS  Google Scholar 

  56. Tripodi A, Caldwell SH, Hoffman M, et al. Review article: the prothrombin time test as a measure of bleeding risk and prognosis in liver disease. Aliment Pharmacol Ther 2007;26:141–8.

    Article  PubMed  CAS  Google Scholar 

  57. Quinlan GJ, Martin GS, Evans TW. Albumin: biochemical properties and therapeutic potential. Hepatology 2005;41:1211–19.

    Article  PubMed  CAS  Google Scholar 

  58. Martin DM, Vroon DH, Nasrallah SM. Value of serum immunoglobulins in the diagnosis of liver disease. Liver 1984;4:214–18.

    PubMed  CAS  Google Scholar 

  59. Yano M, Kumada H, Kage M, et al. The long-term pathological evolution of chronic hepatitis C. Hepatology 1996;23:1334–40.

    Article  PubMed  CAS  Google Scholar 

  60. Strader DB, Wright T, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C. Hepatology 2004;39:1147–71.

    Article  PubMed  Google Scholar 

  61. Vuppalanchi R, Chalasani N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: selected practical issues in their evaluation and management. Hepatology 2009;49:306–17.

    Article  PubMed  Google Scholar 

  62. Thampanitchawong P, Piratvisuth T. Liver biopsy: complications and risk factors. World J Gastroenterol 1999;5:301–4.

    PubMed  Google Scholar 

  63. Regev A, Berho M, Jeffers LJ, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol 2002;97:2614–18.

    Article  PubMed  Google Scholar 

  64. Maharaj B, Maharaj RJ, Leary WP, et al. Sampling variability and its influence on the diagnostic yield of percutaneous needle biopsy of the liver. Lancet 1986;1:523–5.

    Article  PubMed  CAS  Google Scholar 

  65. Goldin RD, Goldin JG, Burt AD, et al. Intra-observer and inter-observer variation in the histopathological assessment of chronic viral hepatitis. J Hepatol 1996;25:649–54.

    Article  PubMed  CAS  Google Scholar 

  66. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007;45:846–54.

    Article  PubMed  CAS  Google Scholar 

  67. Forns X, Ampurdanès S, Llovet JM, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology 2002;36(4 Pt 1):986–92.

    PubMed  Google Scholar 

  68. Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatology 2007;46:32–6.

    Article  PubMed  CAS  Google Scholar 

  69. Halfon P, Bourliere M, Deydier R, et al. Independent prospective multicenter validation of biochemical markers (fibrotest-actitest) for the prediction of liver fibrosis and activity in patients with chronic hepatitis C: the fibropaca study. Am J Gastroenterol 2006;101:547–55.

    Article  PubMed  Google Scholar 

  70. Koda M, Matunaga Y, Kawakami M, et al. FibroIndex, a practical index for predicting significant fibrosis in patients with chronic hepatitis C. Hepatology 2007;45:297–306.

    Article  PubMed  Google Scholar 

  71. Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003;38:518–26.

    Article  PubMed  Google Scholar 

  72. Lackner C, Struber G, Liegl B, et al. Comparison and validation of simple noninvasive tests for prediction of fibrosis in chronic hepatitis C. Hepatology 2005;41:1376–82.

    Article  PubMed  Google Scholar 

  73. Guéchot J, Laudat A, Loria A, et al. Diagnostic accuracy of hyaluronan and type III procollagen amino-terminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluated by ROC curve analysis. Clin Chem 1996;42:558–63.

    PubMed  Google Scholar 

  74. Saitou Y, Shiraki K, Yamanaka Y, et al. Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibrogenesis marker, YKL-40, in patients with HCV-associated liver disease. World J Gastroenterol 2005;11:476–81.

    PubMed  CAS  Google Scholar 

  75. Boeker KH, Haberkorn CI, Michels D, et al. Diagnostic potential of circulating TIMP-1 and MMP-2 as markers of liver fibrosis in patients with chronic hepatitis C. Clin Chim Acta 2002;316:71–81.

    Article  PubMed  CAS  Google Scholar 

  76. Hahn E, Wick G, Pencev D, et al. Distribution of basement membrane proteins in normal and fibrotic human liver: collagen type IV, laminin, and fibronectin. Gut 1980;21:63–71.

    Article  PubMed  CAS  Google Scholar 

  77. Trinchet JC, Hartmann DJ, Pateron D, et al. Serum type I collagen and N-terminal peptide of type III procollagen in chronic hepatitis. Relationship to liver histology and conventional liver tests. J Hepatol 1991;12:139–44.

    Article  PubMed  CAS  Google Scholar 

  78. Misaki M, Shima T, Yano Y, et al. Basement membrane-related and type III procollagen-related antigens in serum of patients with chronic viral liver disease. Clin Chem 1990;36:522–4.

    PubMed  CAS  Google Scholar 

  79. Nelson DR, Gonzalez-Peralta RP, Qian K, et al. Transforming growth factor-beta 1 in chronic hepatitis C. J Viral Hepat 1997;4:29–35.

    Article  PubMed  CAS  Google Scholar 

  80. Calès P, Oberti F, Michalak S, et al. A novel panel of blood markers to assess the degree of liver fibrosis. Hepatology 2005;42:1373–81.

    Article  PubMed  Google Scholar 

  81. Adams LA, Bulsara M, Rossi E, et al. Hepascore: an accurate validated predictor of liver fibrosis in chronic hepatitis C infection. Clin Chem 2005;51:1867–73.

    Article  PubMed  CAS  Google Scholar 

  82. Patel K, Gordon SC, Jacobson I, et al. Evaluation of a panel of non-invasive serum markers to differentiate mild from moderate-to-advanced liver fibrosis in chronic hepatitis C patients. J Hepatol 2004; 41:935–42.

    Article  PubMed  CAS  Google Scholar 

  83. Rosenberg WM, Voelker M, Thiel R, et al. European Liver Fibrosis Group. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology 2004;127:1704–13.

    Article  PubMed  Google Scholar 

  84. Kelleher TB, Mehta SH, Bhaskar R, et al. Prediction of hepatic fibrosis in HIV/HCV co-infected patients using serum fibrosis markers: the SHASTA index. J Hepatol 2005;43:78–84.

    Article  PubMed  Google Scholar 

  85. Del Poggio P, Colombo S. Is transient elastography a useful tool for screening liver disease? World J Gastroenterol 2009 Mar 28;15:1409–14.

    Article  PubMed  Google Scholar 

  86. Castéra L, Foucher J, Bernard PH, et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology 2009 [Epub ahead of print].

    Google Scholar 

  87. Morris-Stiff G, Gomez D, Prasad R. Quantitative assessment of hepatic function and its relevance to the liver surgeon. J Gastrointest Surg 2009;13:374–85.

    Article  Google Scholar 

  88. Mansour A, Watson W, Shayani V, et al. Abdominal operations in patients with cirrhosis: still a major surgical challenge. Surgery 1997;122:730–5; discussion 735–6.

    Article  PubMed  CAS  Google Scholar 

  89. Garrison RN, Cryer HM, Howard DA, et al. Clarification of risk factors for abdominal operations in patients with hepatic cirrhosis. Ann Surg 1984;199:648–55.

    Article  PubMed  CAS  Google Scholar 

  90. Telem DA, Schiano T, Goldstone R, et al. Factors that predict outcome of abdominal operations in patients with advanced cirrhosis. Clin Gastroenterol Hepatol 2010;8:451–7.

    Google Scholar 

  91. Kamath PS, Kim WR. The model for end-stage liver disease (MELD). Advanced Liver Disease Study Group. Hepatology 2007;45:797–805.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Harvard Medical School, Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA

    Hamed Khalili MD & Barham Abu Dayyeh MD

  2. Department of Medicine, Newton-Wellesley Hospital, 2014 Washington Street, Newton, MA, 02462, USA

    Lawrence S. Friedman MD

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  1. Hamed Khalili MD
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  2. Barham Abu Dayyeh MD
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  3. Lawrence S. Friedman MD
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Correspondence to Lawrence S. Friedman MD .

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Editors and Affiliations

  1. Liver Unit, Hospital Clinic, University of Barcelona, Villarroel 170, Barcelona, 08036, Spain

    Pere Ginès

  2. College of Medicine, Division of Gastroenterology and Hepatol, Mayo Clinic, 200 First St. S.W, Rochester, 55905, Minnesota, USA

    Patrick S. Kamath

  3. Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, 08036, Spain

    Vicente Arroyo

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Khalili, H., Dayyeh, B.A., Friedman, L.S. (2011). Assessment of Liver Function in Clinical Practice. In: Ginès, P., Kamath, P., Arroyo, V. (eds) Chronic Liver Failure. Clinical Gastroenterology. Humana Press. https://doi.org/10.1007/978-1-60761-866-9_3

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