Physiological and biochemical basis of clinical liver function tests: A review

Annals of Surgery

Volumn 257, Issue 1, 2013, Pages 27-36

  Hoekstra, Lisette T ^a   De Graaf, Wilmar ^a   Nibourg, Geert A A ^a   Heger, Michal ^a   Bennink, Roelof J ^a   Stieger, Bruno ^a   Van Gulik, Thomas M ^a  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

Compromised liver; functional studies in the liver; liver function tests; mechanistic background; physiological basis

Indexed keywords

ALBUMIN; BILIRUBIN; BLOOD CLOTTING FACTOR; GALACTOSE; INDOCYANINE GREEN; MEBROFENIN TC 99M; TECHNETIUM 99M;

ACCURACY; BIOCHEMISTRY; CLINICAL ASSESSMENT; HEPATOBILIARY SCINTISCANNING; HUMAN; LIVER CLEARANCE; LIVER FAILURE; LIVER FUNCTION TEST; LIVER RESECTION; MORBIDITY; MORTALITY; NUCLEAR MAGNETIC RESONANCE; PHYSIOLOGY; PREDICTION; PREOPERATIVE EVALUATION; PRIORITY JOURNAL; PROTEIN SYNTHESIS; QUANTITATIVE STUDY; REVIEW; SCORING SYSTEM; TREATMENT OUTCOME;

BIOLOGICAL MARKERS; COLORING AGENTS; CONE-BEAM COMPUTED TOMOGRAPHY; HEALTH STATUS INDICATORS; HEPATECTOMY; HUMANS; INDOCYANINE GREEN; LIVER; LIVER FAILURE; LIVER FUNCTION TESTS; PATIENT SELECTION; POSTOPERATIVE COMPLICATIONS; PREOPERATIVE CARE; RADIOPHARMACEUTICALS; TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON;

EID: 84871616495     PISSN: 00034932     EISSN: 15281140     Source Type: Journal    
DOI: 10.1097/SLA.0b013e31825d5d47     Document Type: Review

References (103)

1. Van Den Broek MA, Olde Damink SW, Dejong CH, et al. Liver failure after partial hepatic resection: definition, pathophysiology, risk factors and treat-ment. Liver Int. 2008;28:767-780. (Pubitemid 351818638)
2. Shoup M, Gonen M, D'Angelica M, et al. Volumetric analysis predicts hepatic dysfunction in patients undergoing major liver resection. JGastrointest Surg. 2003;7:325-330. (Pubitemid 36875770)
3. Vauthey JN, Chaoui A, Do KA, et al. Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical associations. Surgery. 2000;127:512-519. (Pubitemid 30257509)
4. Clavien PA, Emond J, Vauthey JN, et al. Protection ofthe liver during hepatic surgery. JGastrointest Surg. 2004;8:313-327. (Pubitemid 38340611)
5. De Graaf W, van Lienden KP, van Gulik TM, et al. (99m)Tc-mebrofenin hepatobiliary scintigraphy with SPECT for the assessment ofhepatic func-tion and liver functional volume before partial hepatectomy J Nucl Med. 2010;51:229-236.
6. De Graaf W, van Lienden KP, Dinant S, et al. Assessment of future remnant liver function using hepatobiliary scintigraphy in patients undergoing major liverresection. JGastrointest Surg. 2010;14:369-378.
7. Schindl MJ, Millar AM, Redhead DN, et al. The adaptive response of the reticuloendothelial system to major liver resection in humans. Ann Surg. 2006;243:507-514.
8. Demetriou AA, Brown RS Jr, Busuttil RW, et al. Prospective, randomized, multicenter, controlled trial of a bioartificial liver intreating acute liver failure. Ann Surg. 2004;239:660-667.
9. van de Kerkhove MP, Hoekstra R, Chamuleau RA, et al. Clinical application ofbioartificial liver support systems. Ann Surg. 2004;240:216-230. (Pubitemid 38963011)
10. Rahbari NN, Garden OJ, Padbury R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011;149:713-724.
11. Fan ST. Liver functional reserve estimation: state of the art and relevance for local treatments: the Eastern perspective. JHepatobiliary Pancreat Sci. 2010;17:380-384.
12. Chand N, Sanyal AJ. Sepsis-induced cholestasis. Hepatology. 2007;45:230-241. (Pubitemid 46144383)
13. Field KM, Dow C, Michael M. Part I: liver function in oncology: biochemistry andbeyond. Lancet Oncol. 2008;9:1092-1101.
14. Cui Y, Konig J, Leier I, et al. Hepatic uptake of bilirubin and its conjugates by thehumanorganic aniontransporter SLC21A6. JBiol Chem. 2001;276:9626-9630.
15. De Graaf W, Hausler S, Heger M, et al. Transporters involved in the hepatic up-take of(99m)Tc-mebrofeninandindocyanine green. JHepatol. 2011;54:738-745.
16. Briz O, Serrano MA, Mac Ias RI, et al. Role oforganic anion-transporting polypeptides, OATP-A, OATP-C and OATP-8, in the human placenta-maternal liver tandem excretory pathway for foetal bilirubin. Biochem J. 2003;371:897-905. (Pubitemid 36578888)
17. Wang P, Kim RB, Chowdhury JR, et al. The human organic anion trans-port protein SLC21A6 is not sufficient for bilirubin transport. J Biol Chem. 2003;278:20695-20699. (Pubitemid 36806371)
18. Johnson AD, Kavousi M, Smith AV, et al. Genome-wide association meta-analysis for total serum bilirubin levels. Hum Mol Genet. 2009;18:2700-2710.
19. Sanna S, Busonero F, Maschio A, et al. Common variants in the SLCO1B3 lo-cus are associated with bilirubin levels and unconjugated hyperbilirubinemia. Hum Mol Genet. 2009;18:2711-2718.
20. Zhang W, He YJ, Gan Z, et al. OATP1B1 polymorphism is a major deter-minant ofserum bilirubin level but not associated with rifampicin-mediated bilirubin elevation. Clin Exp Pharmacol Physiol. 2007;34:1240-1244. (Pubitemid 350013247)
21. van de Steeg E, Wagenaar E, van der Kruijssen CM, et al. Organic anion transporting polypeptide 1a/1b-knockout mice provide insights into hepatic handling ofbilirubin, bile acids, and drugs. J Clin Invest. 2010;120:2942-2952.
22. Csanaky IL, Lu H, Zhang Y, et al. Organic anion-transporting polypeptide 1b2 (Oatp1b2) is important for the hepatic uptake ofunconjugated bile acids: studies in Oatp1b2-null mice. Hepatology. 2011;53:272-281.
23. Zaher H, Meyer zu Schwabedissen HE, Tirona RG, et al. Targeted disruption ofmurine organic anion-transporting polypeptide 1b2 (Oatp1b2/Slco1b2) significantly alters disposition ofprototypical drug substrates pravastatin and rifampin. Mol Pharmacol. 2008;74:320-329.
24. De Graaf W, Bennink RJ, Heger M, et al. Quantitative assessment ofhepatic function during liver regeneration in a standardized rat model. J Nucl Med. 2011;52:294-302.
25. Krishnamurthy GT, Krishnamurthy S. Cholescintigraphic measurement of liver function: how is it different from other methods? Eur J Nucl Med Mol Imaging. 2006;33:1103-1106. (Pubitemid 44484465)
26. Tanaka Y, Chen C, Maher JM, et al. Kupffer cell-mediated downregulation ofhepatic transporter expression in rat hepatic ischemia-reperfusion. Trans-plantation. 2006;82:258-266. (Pubitemid 44126824)
27. Lau WY. Hepatocellular Carcinoma. Singapore: World Scientific Publishing Company; 2008.
28. Schneider PD. Preoperative assessment ofliver function. Surg Clin North Am. 2004;84:355-373.
29. Nagashima I, Takada T, Okinaga K, et al. A scoring system for the assessment ofthe risk ofmortality after partial hepatectomy in patients with chronic liver dysfunction. JHepatobiliary Pancreat Surg. 2005;12:44-48. (Pubitemid 40378840)
30. Garcea G, Ong SL, Maddern GJ. Predicting liver failure following major hepatectomy. Dig Liver Dis. 2009;41:798-806.
31. Clavien PA, Petrowsky H, De Oliveira ML, et al. Strategies for safer liver surgery and partial liver transplantation.N Engl J Med.2007;356:1545-1559. (Pubitemid 46588419)
32. Faybik P, Hetz H. Plasma disappearance rate of indocyanine green in liver dysfunction. Transplant Proc. 2006;38:801-802.
33. Wissler EH. Identifying a long standing error in single-bolus determination of the hepatic extraction ratio for indocyanine green. Eur J Appl Physiol. 2011;111:641-646.
34. Paumgartner G. The handling ofindocyanine green by the liver. Schweiz Med Wochenschr. 1975;105:1-30.
35. Sakka SG, Reinhart K, Meier-Hellmann A. Prognostic value of the indo-cyanine green plasma disappearance rate in critically ill patients. Chest. 2002;122:1715-1720. (Pubitemid 35366087)
36. Sathirakul K, Suzuki H, Yasuda K, et al. Kinetic analysis ofhepatobiliary transport of organic anions in Eisai hyperbilirubinemic mutant rats. JPhar-macol Exp Ther. 1993;265:1301-1312. (Pubitemid 23321033)
37. Sakka SG. Assessing liver function. Curr Opin Crit Care. 2007;13:207-214. (Pubitemid 46328337)
38. Okochi O, Kaneko T, Sugimoto H, et al. ICG pulse spectrophotome-try for perioperative liver function in hepatectomy J Surg Res. 2002;103: 109-113. (Pubitemid 34953399)
39. Akita H, Sasaki Y, Yamada T, et al. Real-time intraoperative assessment of residual liver functional reserve using pulse dye densitometry. World J Surg. 2008;32:2668-2674.
40. Burra P, Masier A. Dynamic tests to study liver function. Eur Rev Med Pharmacol Sci. 2004;8:19-21. (Pubitemid 38659918)
41. Imamura H, Sano K, Sugawara Y, et al. Assessment ofhepatic reserve for indication ofhepatic resection: decision tree incorporating indocyanine green test. JHepatobiliary Pancreat Surg. 2005;12:16-22. (Pubitemid 40378835)
42. Kortgen A, Paxian M, Werth M, et al. Prospective assessment ofhepatic func-tionandmechanisms of dysfunctioninthe criticallyill. Shock. 2009;32:358-365.
43. Watanabe Y, Kumon K. Assessment by pulse dye-densitometry indocyanine green (ICG) clearance test of hepatic function of patients before cardiac surgery: its value as a predictor of serious postoperative liver dysfunction. J Cardiothorac Vasc Anesth. 1999;13:299-303. (Pubitemid 29283381)
44. Lau H, Man K, Fan ST, et al. Evaluation ofpreoperative hepatic function in patients with hepatocellular carcinoma undergoing hepatectomy. Br J Surg. 1997;84:1255-1259. (Pubitemid 27400276)
45. Inderbitzin D, Muggli B, Ringger A, et al. Molecular absorbent recirculating system for the treatment ofacute liver failure in surgical patients. JGastroin-test Surg. 2005;9:1155-1161.
46. Lam CM, Fan ST, Lo CM, et al. Major hepatectomy for hepatocellular carci-noma in patients with an unsatisfactory indocyanine green clearance test. Br J Surg. 1999;86:1012-1017. (Pubitemid 29387065)
47. 99mTc-GSA) liver scintigraphy. Hepatology. 1997;25:426-429. (Pubitemid 27069066)
48. Fan ST, Lai EC, Lo CM, et al. Hospital mortality of major hepatectomy for hepatocellularcarcinomaassociatedwithcirrhosis. Arch Surg. 1995;130:198-203.
49. Sawada T, Kita J, Nagata H, et al. Hepatectomy for metastatic liver tumor in patients with liver dysfunction. Hepatogastroenterology. 2007;54:2306-2309.
50. Geier A, Wagner M, Dietrich CG, et al. Principles ofhepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration. Biochim Biophys Acta. 2007;1773:283-308. (Pubitemid 46275063)
51. Goresky CA, Bach GG, Nadeau BE. On the uptake of materials by the intact liver. Thetransportandnetremoval ofgalactose. JClin Invest. 1973;52:991-1009.
52. Holden HM, Rayment I, Thoden JB. Structure and function of enzymes of the Leloir pathway for galactosemetabolism.JBiol Chem. 2003;278:43885-43888. (Pubitemid 37377125)
53. Herold C, Heinz R, Niedobitek G, et al. Quantitative testing ofliver func-tion in relation to fibrosis in patients with chronic hepatitis B and C. Liver. 2001;21:260-265. (Pubitemid 32677382)
54. Redaelli CA, Dufour JF, Wagner M, et al. Preoperative galactose elimination capacitypredicts complications andsurvival afterhepatic resection. Ann Surg. 2002;235:77-85. (Pubitemid 34062402)
55. Ranek L, Andreasen PB, Tygstrup N. Galactose elimination capacity as a prognostic index in patients with fulminant liver failure. Gut. 1976;17:959-964.
56. Reichen J, Widmer T, Cotting J. Accurate prediction of death by serial de-termination ofgalactose elimination capacity in primary biliary cirrhosis: a comparison with the Mayo model. Hepatology. 1991;14:504-510.
57. Tengstrom B. The discriminatory ability of a galactose tolerance test and some other tests in the diagnosis of cirrhosis of the liver, hepatitis and biliary obstruction. Scand JClin Lab Invest. 1969;23:159-168.
58. Jepsen P, Vilstrup H, Ott P, et al. The galactose elimination capacity and mortalityin781 Danishpatientswithnewly-diagnosedlivercirrhosis:acohort study. BMC Gastroenterol. 2009;9:50.
59. Aebli N, Reichen J. The prognostic value of the serial determination ofgalac-tose elimination capacity in chronic active hepatitis [in German]. Schweiz Med Wochenschr. 1991;121:970-976.
60. Jansen PL, Chamuleau RA, van Leeuwen DJ, et al. Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors. Scand J Gastroenterol. 1990;25:112-118. (Pubitemid 20202967)
61. Kokudo N, Vera DR, Tada K, et al. Predictors ofsuccessfulhepatic resection: prognostic usefulness ofhepatic asialoglycoprotein receptor analysis. World J Surg. 2002;26:1342-1347. (Pubitemid 36920228)
62. Kudo M, Todo A, Ikekubo K, et al. Quantitative assessment of hepatocel-lular function through in vivo radioreceptor imaging with technetium 99m galactosyl human serum albumin. Hepatology. 1993;17:814-819. (Pubitemid 23150090)
63. Akaki S, Mitsumori A, Kanazawa S, et al. Technetium-99m-DTPA-galactosyl human serum albumin liver scintigraphy evaluation ofregional CT/MRI at-tenuation/signal intensity differences. J Nucl Med. 1998;39:529-532. (Pubitemid 28136857)
64. Ashwell G, Steer CJ. Hepatic recognition and catabolism of serum glycopro-teins.JAMA. 1981;246:2358-2364.
65. Hubbard AL, Wilson G, Ashwell G, et al. An electron microscope autora-diographic study ofthe carbohydrate recognition systems in rat liver, part I: distribution of I-ligands among the liver cell types. J Cell Biol. 1979;83:47-64. (Pubitemid 10197033)
66. Stockert RJ, Morell AG. Hepatic binding protein: the galactose-specific re-ceptor of mammalian hepatocytes. Hepatology. 1983;3:750-757. (Pubitemid 13007704)
67. Sawamura T, Kawasato S, Shiozaki Y, et al. Decrease of a hepatic binding protein specific for asialoglycoproteins with accumulation of serum asialo-glycoproteins in galactosamine-treated rats. Gastroenterology. 1981;81:527-533. (Pubitemid 11061553)
68. Suzuki Y, Kohno Y, Takeda Y, et al. Evaluation ofliver function parameters by Tc-99m-GSA using multivariate analysis: a study of47 clinical cases. Acta Med Okayama. 1999;53:225-232. (Pubitemid 129538473)
69. Kawamura H, Kamiyama T, Nakagawa T, et al. Preoperative evaluation of hepatic functional reserve by converted ICGR15 calculated from Tc-GSA scintigraphy. J Gastroenterol Hepatol. 2008;23:1235-1241.
70. 99m Tc-galactosyl-human serum albumin for prognosis of cirrhosis of the liver. J Nucl Med. 1999;40:1652-1656. (Pubitemid 29471155)
71. Kwon AH, Ha-Kawa SK, Uetsuji S, et al. Use of technetium 99m diethylenetriamine-pentaacetic acid-galactosyl-human serum albumin liver scintigraphy in the evaluation ofpreoperative and postoperative hepatic func-tionalreserve for hepatectomy Surgery. 1995;117:429-434.
72. Nanashima A, Yamaguchi H, Shibasaki S, et al. Relationship between in-docyanine green test and technetium-99m galactosyl serum albumin scintig-raphy in patients scheduled for hepatectomy: clinical evaluation and patient outcome. Hepatol Res. 2004;28:184-190. (Pubitemid 38351912)
73. Mimura T, Hamazaki K, Sakai H, et al. Evaluation of hepatic functional reserve in rats with obstructivejaundice by asyaloglycoprotein receptor. Hep-atogastroenterology. 2001;48:777-782. (Pubitemid 32619680)
74. De Graaf W, Bennink RJ, Vetelainen R, et al. Nuclear imaging techniques for the assessment ofhepatic function in liver surgery and transplantation. J Nucl Med. 2010;51:742-752.
75. Kokudo N, Vera DR, Makuuchi M. Clinical application of Tc GSA. Nucl Med Biol. 2003;30:845-849.
76. Tanaka A, Shinohara H, Hatano E, et al. Perioperative changes in hepatic func-tion as assessed by asialoglycoprotein receptor indices by technetium 99m galactosyl human serum albumin. Hepatogastroenterology. 1999;46:369-375. (Pubitemid 29154779)
77. Kim YK, Nakano H, Yamaguchi M, et al. Prediction ofpostoperative decom-pensated liver function by technetium-99m galactosyl-human serum albumin liver scintigraphy in patients with hepatocellular carcinoma complicating chronic liver disease. Br J Surg. 1997;84:793-796. (Pubitemid 27235259)
78. Takeuchi S, Nakano H, Kim YK, et al. Predicting survival and post-operative complications with Tc-GSA liver scintigraphy in hepatocellular carcinoma. Hepatogastroenterology. 1999;46:1855-1861. (Pubitemid 29366360)
79. Mitsumori A, Nagaya I, Kimoto S, et al. Preoperative evaluation ofhepatic functional reserve following hepatectomy by technetium-99m galactosyl hu-man serum albumin liver scintigraphy and computed tomography Eur J Nucl Med. 1998;25:1377-1382. (Pubitemid 28464111)
80. Kwon AH, Matsui Y, Ha-Kawa SK, et al. Functional hepatic volume mea-sured by technetium-99m-galactosyl-human serum albumin liver scintigra-phy: comparison between hepatocyte volume and liver volume by computed tomography Am J Gastroenterol. 2001;96:541-546.
81. Sato S, Mimura H, Noda T, et al. Studyofquantitativeevaluationoflivervol- ume and accumulation rate ofradioactive agent with single photon emission computedtomography [in Japanese]. Radioisotopes. 1987;36:265-269.
82. 99mTc-GSA liver dynamic SPECT for the preoperative assessment ofhepatectomy. Ann Nucl Med. 2003;17:61-67. (Pubitemid 36417575)
83. Akaki S, Okumura Y, Sasai N, et al. Hepatectomy simulation discrepancy between radionuclide receptor imaging and CT volumetry: influence of de-creased unilateral portal venous flow. Ann Nucl Med. 2003;17:23-29. (Pubitemid 36417570)
84. Li XF, Taki J, Kinuya S, et al. Asialoglycoprotein receptor concentration in tumor-bearing livers and its fate early after their sectorial resection. Ann Nucl Med. 2003;17:489-493. (Pubitemid 37221592)
85. 99mTc-DTPA-galactosyl-human serum albumin dynamic SPECT. J Nucl Med. 1999;40:1644-1651. (Pubitemid 29471154)
86. Krishnamurthy S, Krishnamurthy GT. Technetium-99m-iminodiacetic acid organic anions: review ofbiokinetics and clinical application in hepatology. Hepatology. 1989;9:139-153. (Pubitemid 19046316)
87. Dinant S, de Graaf W, Verwer BJ, et al. Risk assessment of posthepatectomy liver failure using hepatobiliary scintigraphy and CT volumetry. J Nucl Med. 2007;48:685-692. (Pubitemid 47604966)
88. Trauner M, Meier PJ, Boyer JL. Molecular pathogenesis of cholestasis. N Engl J Med. 1998;339:1217-1227.
89. Hendrikse NH, Kuipers F, Meijer C, et al. In vivo imaging ofhepatobiliary transport function mediated by multidrug resistance associated protein and P-glycoprotein. Cancer Chemother Pharmacol. 2004;54:131-138. (Pubitemid 39044242)
90. Krishnamurthy S, Krishnamurthy GT, Lieberman D, et al. Scintigraphic cri-teria for the diagnosis of obstructive hepatobiliary diseases with Tc-99m IDA. Clin Nucl Med. 1988;13:704-709.
91. Krishnamurthy GT, Lieberman DA, Brar HS. Detection, localization, and quantitation of degree of common bile duct obstruction by scintigraphy. J Nucl Med. 1985;26:726-735. (Pubitemid 16005494)
92. Heyman S. Hepatobiliary scintigraphy as a liver function test. J Nucl Med. 1994;35:436-437. (Pubitemid 24079971)
93. Ekman M, Fjalling M, Holmberg S, et al. IODIDA clearancerate: amethodfor measuringhepatocyteuptakefunction. Transplant Proc. 1992;24:387-388.
94. Bennink RJ, Dinant S, Erdogan D, et al. Preoperative assessment of postop-erative remnant liver function using hepatobiliary scintigraphy J Nucl Med. 2004;45:965-971. (Pubitemid 47611683)
95. 99mTc-Mebrofenin scintigraphy with indocyanine green clearance test. Liver Int. 2004;24:117-123. (Pubitemid 38584997)
96. De Graaf W, Van Lienden KP, Van Den Esschert JW, et al. Increase in future remnant liver function after preoperative portal vein embolization. Br J Surg. 2011;98:825-834.
97. Lan JA, Chervu LR, Johansen KL, et al. Uptake oftechnetium 99m hep-atobiliary imaging agents by cultured rat hepatocytes. Gastroenterology. 1988;95:1625-1631. (Pubitemid 19016225)
98. Vetelainen R, van VA, Gouma DJ, et al. Steatosis as a risk factor in liver surgery. Ann Surg. 2007;245:20-30. (Pubitemid 46035431)
99. Seifalian AM, El-Desoky A, Davidson BR. Hepatic indocyanine greenuptake andexcretioninarabbitmodel ofsteatosis. Eur Surg Res. 2001;33:193-201. (Pubitemid 32722272)
100. Brenner DA, Waterboer T, Choi SK, et al. New aspects of hepatic fibrosis. J Hepatol. 2000;32:32-38. (Pubitemid 30123622)
101. Brenner DA. Molecularpathogenesisofliverfibrosis. Trans Am Clin Climatol Assoc. 2009;120:361-368.
102. Mullin EJ, Metcalfe MS, Maddern GJ. How much liver resection is too much? Am J Surg. 2005;190:87-97. (Pubitemid 40828612)
103. Heger M, de Graaf W, Bennink RJ, et al. A clinical perspective on the criteria for liver resection and the use ofliver function tests. World J Surg. 2010;34:868-869.