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Chapter 7 - Laboratory Assessment of Liver Function and Injury in Children

from Section I - Pathophysiology of Pediatric Liver Disease

Published online by Cambridge University Press:  19 January 2021

By
Vicky Lee Ng
Edited by
Frederick J. Suchy ,
Ronald J. Sokol  and
William F. Balistreri
Edited in association with
Jorge A. Bezerra ,
Cara L. Mack  and
Benjamin L. Shneider
Frederick J. Suchy
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Ronald J. Sokol
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
William F. Balistreri
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Jorge A. Bezerra
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Cara L. Mack
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Benjamin L. Shneider
Affiliation:
Texas Children’s Hospital, Houston
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Summary

The liver is a multifunctional organ that is involved in a number of critical excretory, synthetic and metabolic functions. Biochemical assessment of these functions in children is undertaken by utilizing a number of tests performed in clinical laboratories. Many of the most commonly utilized serum chemistry tests, like aminotransferase and alkaline phosphatase levels, are often referred to as liver function tests (LFTs), which is a misnomer, as these do not actually measure or indicate liver function. Rather, these tests should be referred to as liver enzyme tests, reserving the term LFTs to refer to measures of hepatocyte synthetic function such as international normalized ratio (INR), prothrombin time (PT) or serum albumin. Any single biochemical test provides limited information, which must be placed in the context of the entire clinical and historic picture. Currently, the most commonly available laboratory evaluative tests of the liver are used to: (1) screen for and document liver injury; (2) identify the type or pattern of liver disorder and the site of injury; (3) prognosticate and follow-up children with chronic liver disease; and (4) serially monitor the course of liver disease, evaluate the response to treatment and adjust a treatment regimen, when appropriate. Tests to evaluate liver disease can be divided into five categories (Table 7.1)

Type
Chapter
Information
Liver Disease in Children , pp. 94 - 106
Publisher: Cambridge University Press
Print publication year: 2021

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References

Adams, PC, Arthur, MJ, Boyer, TD, DeLeve, LD, Di Bisceglie, AM, Hall, M, Seeff, L. Screening in liver disease: report of an AASLD clinical workshop. Hepatology 2004;39(5):1204–12. doi:10.1002/hep.20169Google Scholar
Adeli, K, Higgins, V, Trajcevski, K, White-Al Habeeb, N. The Canadian laboratory initiative on pediatric reference intervals: A CALIPER white paper. Crit Rev Clin Lab Sci 2017;54(6):358–413.Google Scholar
Agarwal, B, Wright, G, Gatt, A, Riddell, A, Vemala, V, Mallett, S, Burroughs, A. Evaluation of coagulation abnormalities in acute liver failure. J Hepatol 2012;57(4):780–6. doi:10.1016/j.jhep.2012.06.020CrossRefGoogle ScholarPubMed
Ahn, H, Li, CS, Wang, W. Sickle cell hepatopathy: clinical presentation, treatment, and outcome in pediatric and adult patients. Pediatr Blood Cancer 2005;45(2):184–90. doi:10.1002/pbc.20317CrossRefGoogle ScholarPubMed
Bamford, KF, Harris, H, Luffman, JE, Robson, EB, Cleghorn, TE Serum-alkaline-phosphatase and the abo blood-groups. Lancet 1965;1(7384):530–1.Google ScholarPubMed
Banks, BM, Pineda, EP, Goldbarg, JA, Rutenburg, AM. Clinical value of serum leucine aminopeptidase determinations. N Engl J Med 1960;263:1277–81. doi:10.1056/NEJM196012222632503CrossRefGoogle ScholarPubMed
Berman, DH, Leventhal, RI, Gavaler, JS, Cadoff, EM, Van Thiel, DH. Clinical differentiation of fulminant Wilsonian hepatitis from other causes of hepatic failure. Gastroenterology 1991;100(4):1129–34. doi:S0016508591001348Google Scholar
Burra, P, Masier, A. Dynamic tests to study liver function. Eur Rev Med Pharmacol Sci 2004;8(1):19–21.Google ScholarPubMed
Bussler, S, et al. New pediatric percentiles of liver enzyme serum levels. Hepatology 2017;68:1319–30.Google Scholar
Cabrera-Abreu, JC, Green, A. Gamma-glutamyltransferase: value of its measurement in paediatrics. Ann Clin Biochem 2002;39(Pt 1):22–5.Google Scholar
Chambers, JC, Zhang, W, Sehmi, J, Li, X, Wass, MN, Van der Harst, P, Kooner, JS. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat Genet 2011;43(11):1131–8.Google Scholar
Ciobanu, AO, Gherasim, L. Ischemic hepatitis – intercorrelated pathology. Maedica 2018;13(1):5–11.CrossRefGoogle ScholarPubMed
Croffie, JM, Gupta, SK, Chong, SK, Fitzgerald, JF. Tyrosinemia type 1 should be suspected in infants with severe coagulopathy even in the absence of other signs of liver failure. Pediatrics 1999;103(3):675–8.CrossRefGoogle ScholarPubMed
Dasarathy, S, Mookerjee, RP, Rackayova, V, Rangroo Thrane, V, Vairappan, B, Ott, P, Rose, CF. Ammonia toxicity: from head to toe? Metab Brain Dis 2017;32(2):529–38. doi:10.1007/s11011-016-9938-3Google Scholar
Deutsch, J, Fritsch, G, Golles, J, Semmelrock, HJ. Effects of anticonvulsive drugs on the activity of gammaglutamyltransferase and aminotransferases in serum. J Pediatr Gastroenterol Nutr 1986;5(4):542–8.Google Scholar
Di Ciaula, A, Garruti, G, Lunardi Baccetto, R, Molina-Molina, E, Bonfrate, L, Wang, DQ, Portincasa, P. Bile acid physiology. Ann Hepatol 2017;16(Suppl. 1):s3–105, s4–s14. doi:10.5604/01.3001.0010.5493Google Scholar
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 1984;86(4):632–6. doi:S0016508584000809CrossRefGoogle ScholarPubMed
Dixon, JL, Ginsberg, HN. Hepatic synthesis of lipoproteins and apolipoproteins. Semin Liver Dis 1992;12(4):364–72. doi:10.1055/s-2008-1040406CrossRefGoogle ScholarPubMed
Ebrahimi, A, Rahim, F. Crigler-Najjar syndrome: current perspectives and the application of clinical genetics. Endocr Metab Immune Disord Drug Targets 2018;18(3):201–11. doi:10.2174/1871530318666171213153130Google Scholar
Ekong, UD, et al. Long-term outcomes of de novo autoimmune hepatitis in pediatric liver transplant recipients. Pediatr Transplant 2017;21(6):e12945. https://doi.org/10.1111/petr.12945Google Scholar
Eymann, A, Cacchiarelli, N, Alonso, G, Llera, J. Benign transient hyperphosphatasemia of infancy. A common benign scenario, a big concern for a pediatrician. J Pediatr Endocrinol Metab 2010;23(9):927–30.CrossRefGoogle ScholarPubMed
Farre, C, Esteve, M, Curcoy, A, Cabre, E, Arranz, E, Amat, LL, Garcia-Tornel, S. Hypertransaminasemia in pediatric celiac disease patients and its prevalence as a diagnostic clue. Am J Gastroenterol 2002;97(12):3176–81. doi:10.1111/j.1572-0241.2002.07127CrossRefGoogle ScholarPubMed
Fawaz, R, Baumann, U, Ekong, U, Fischler, B, Hadzic, N, Mack, CL, Karpen, SJ. Guideline for the Evaluation of Cholestatic Jaundice in Infants: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2017;64(1):154–68. doi:10.1097/mpg.0000000000001334CrossRefGoogle Scholar
Feldman, AG, Sokol, RJ. Neonatal cholestasis: emerging molecular diagnostics and potential novel therapeutics. Nat Rev Gastroenterol Hepatol 2019;16(6):346–60. doi:10.1038/s41575-019-0132-zGoogle Scholar
Fellin, R, Manzato, E. Lipoprotein-X fifty years after its original discovery. Nutr Metab Cardiovasc Dis 2019;29(1):4–8. doi:10.1016/j.numecd.2018.09.006Google Scholar
Fujiwara, R, Haag, M, Schaeffeler, E, Nies, AT, Zanger, UM, Schwab, M. Systemic regulation of bilirubin homeostasis: potential benefits of hyperbilirubinemia. Hepatology 2018;67(4):1609–19. doi:10.1002/hep.29599Google Scholar
Furuya, KN, Durie, PR, Roberts, EA, Soldin, SJ, Verjee, Z, Yung-Jato, L, Ellis, L. Glycine conjugation of para-aminobenzoic acid (PABA): a quantitative test of liver function. Clin Biochem 1995;28(5):531–40. doi:0009-9120(95)00040-GCrossRefGoogle Scholar
Harrison, MF. The misunderstood coagulopathy of liver disease: a review for the acute setting. West J Emerg Med 2018;19(5):863–71. doi:10.5811/westjem.2018.7.37893Google Scholar
Heubi, JE, Setchell, KDR., Bove, KE. Inborn errors of bile acid metabolism. Clin Liver Dis 2018;22(4):671–87. doi:10.1016/j.cld.2018.06.006Google Scholar
Hill, PG, Sammons, HG. An assessment of 5′-nucleotidase as a liver-function test. Q J Med 1967;36(144):457–68.Google Scholar
Hoofnagle, JH, Bjornsson, ES. Drug-induced liver injury – types and phenotypes. N Engl J Med 2019;381(3):264–73. doi:10.1056/NEJMra1816149CrossRefGoogle ScholarPubMed
Iorio, R, Sepe, A, Giannattasio, A, Cirillo, F, Vegnente, A. Hypertransaminasemia in childhood as a marker of genetic liver disorders. J Gastroenterol 2005;40(8):820–6. doi:10.1007/s00535-005-1635-7CrossRefGoogle ScholarPubMed
Kaplan, MM. Alkaline phosphatase. Gastroenterology 1972;62(3):452–68.Google Scholar
Kawada, PS, Bruce, A, Massicotte, P, Bauman, M, Yap, J. Coagulopathy in children with liver disease. J Pediatr Gastroenterol Nutr 2017;65(6):603–7. doi:10.1097/mpg.0000000000001721Google Scholar
Keller, MS, Coln, CE, Trimble, JA, Green, MC, Weber, TR. The utility of routine trauma laboratories in pediatric trauma resuscitations. Am J Surg 2004;188(6):671–8.Google Scholar
Kohli, R, Cortes, M, Heaton, ND, Dhawan, A. Liver transplantation in children: state of the art and future perspectives. Arch Dis Child 2018;103(2): 192–8. doi:10.1136/archdischild-2015-310023CrossRefGoogle ScholarPubMed
Kohse, KP. KIGGS – the German survey on children’s health as database for reference intervals and beyond. Circ Biochem 2014;47:742–3.Google Scholar
Krawczyk, M, Mullenbach, R, Weber, SN, Zimmer, V, Lammert, F. Genome-wide association studies and genetic risk assessment of liver diseases. Nat Rev Gastroenterol Hepatol 2010;7(12):669–81.CrossRefGoogle ScholarPubMed
Kunutsor, SK. Gamma-glutamyltransferase: friend or foe within? Liver Int 2016;36(12):1723–34. doi:10.1111/liv.13221Google Scholar
Kwo, PY, Cohen, SM, Lim, JK. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol 2017;112(1):18–35. doi:10.1038/ajg.2016.517Google Scholar
Lebel, S, Nakamachi, Y, Hemming, A, Verjee, Z, Phillips, MJ, Furuya, KN. Glycine conjugation of para-aminobenzoic acid (PABA): a pilot study of a novel prognostic test in acute liver failure in children. J Pediatr Gastroenterol Nutr 2003;36(1):62–71.Google Scholar
Lee, GJ, Boyle, B, Ediger, T, Hill, I. Hypertransaminasemia in newly diagnosed pediatric patients with celiac disease. J Pediatr Gastroenterol Nutr 2016;63(3):340–3. doi:10.1097/mpg.0000000000001153Google Scholar
Li, X, Wang, D, Yang, C, Zhou, Q, Zhuoga, SL, Wang, LQ, Yao, HX, Zhang, Q, Ai, Q, Yang, CX, Xu, JC. Establishment of age- and gender-specific pediatric reference intervals for liver function tests in healthy Han children. World J Pediatr 2018;14(2):151–9. doi: 10.1007/s12519-018-0126CrossRefGoogle ScholarPubMed
Lightsey, JM, Rockey, DC. Current concepts in ischemic hepatitis. Curr Opin Gastroenterol 2017;33(3):158–63. doi:10.1097/mog.0000000000000355CrossRefGoogle ScholarPubMed
Lisman, T, Porte, RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010;116(6):878–85. doi:blood-2010-02-261891CrossRefGoogle ScholarPubMed
Lontie, JF, Dubois, DY, Malmendier, CL, Mathe, D, Adam, R, Gigou, M, Bismuth, H. Plasma lipids and apolipoproteins in end-stage liver disease. Clin Chim Acta 1990;195(1–2):93–6.CrossRefGoogle ScholarPubMed
Maggiore, G, Bernard, O, Hadchouel, M, Lemonnier, A, Alagille, D. Diagnostic value of serum gamma-glutamyl transpeptidase activity in liver diseases in children. J Pediatr Gastroenterol Nutr 1991;12(1):21–6.Google Scholar
Mencin, AA, Lavine, JE.. Nonalcoholic fatty liver disease in children. Curr Opin Clin Nutr Metab Care 2011;14(2):151–7. doi:10.1097/MCO.0b013e328342baecGoogle Scholar
Miller, JP. Dyslipoproteinaemia of liver disease. Baillieres Clin Endocrinol Metab 1990;4(4):807–32.Google Scholar
Nicastro, E, D’Antiga, L. Next generation sequencing in pediatric hepatology and liver transplantation. Liver Transplantation 2018;24(2):282–93.Google Scholar
Newsome, PN, Cramb, R, Davison, S, et al. Guidelines on the management of abnormal liver blood tests. Gut 2018;67:6–19.Google Scholar
O’Leary, JG, Greenberg, CS, Patton, HM, Caldwell, SH. AGA clinical practice update: coagulation in cirrhosis. Gastroenterology 2019;157(1): 34–43.e31. doi:10.1053/j.gastro.2019.03.070Google Scholar
Orlando, R, Palatini, P. The effect of age on plasma MEGX concentrations. Br J Clin Pharmacol 1997;44(2):206–8.CrossRefGoogle ScholarPubMed
Poustchi, H, George, J, Esmaili, S, Esna-Ashari, F, Ardalan, G, Sepanlou, SG, Alavian, SM. Gender differences in healthy ranges for serum alanine aminotransferase levels in adolescence. PLoS One 2011;6(6):e21178. doi: 10.1371/journal.pone.0021178Google Scholar
Rosenthal, P, Haight, M. Aminotransferase as a prognostic index in infants with liver disease. Clin Chem 1990;36(2):3468.CrossRefGoogle ScholarPubMed
Schwimmer, JB, Dunn, W, Norman, GJ, Pardee, PE, Middleton, MS, Kerkar, N, Sirlin, CB. SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology 2010;138(4):1357–64, 1364 e1351–1352.CrossRefGoogle ScholarPubMed
Seidel, D. Lipoproteins in liver disease. J Clin Chem Clin Biochem 1987;25(9):541–51.Google Scholar
Setchell KD, O’Connell NC. (2018). Bile acid synthesis and metabolism. In Kleinman RE, Goulet OJ, Mieli-Vergani G, Sanderson IR, Sherman PM, Shneider BL (Eds.), Walker’s Pediatric Gastrointestinal Disease: Physiology, Diagnosis, Management, 6th Edition. PMPH USA, Ltd.Google Scholar
Sharma, U, Pal, D, Prasad, R. Alkaline phosphatase: an overview. Indian J Clin Biochem 2014;29(3):269–78. doi:10.1007/s12291-013-0408Google Scholar
Stirnadel-Farrant, HA, Galwey, N, Bains, C, Yancey, C, Hunt, CM. Children’s liver chemistries vary with age and gender and require customized pediatric reference ranges. Regul Toxicol Pharmacol 2015;73(1):349–55. doi: 10.1016/j.yrtph.2015.07.013Google Scholar
Sookoian, S, Pirola, CJ. Liver enzymes, metabolomics and genome-wide association studies: from systems biology to personalized medicine. World J Gastroenterol 2015;21(3):711–25. doi:10.3748/wjg.v21.i3.711Google Scholar
Solez, K, et al. The bridge between transplantation and regenerative medicine: beginning a new Banff classification of tissue engineering pathology. Am J Transplant 2018;18(2):321–7. doi: 10.1111/ajt.14610Google Scholar
Spinella, R, Sawhney, R, Jalan, R. Albumin in chronic liver disease: structure, functions and therapeutic implications. Hepatol Int 2016;10(1):124–32. doi:10.1007/s12072-015-9665-6Google Scholar
Squires, JE, McKiernan, P. Molecular mechanisms in pediatric cholestasis. Gastroenterol Clin North Am 2018;47(4):921–37. doi:10.1016/j.gtc.2018.07.014Google Scholar
Squires, JE, McKiernan, P, Squires, RH. Acute liver failure: an update. Clin Liver Dis 2018;22(4):773–805. doi:10.1016/j.cld.2018.06.009Google Scholar
Tate, JR, et al. Harmonising adult and paediatric reference intervals in Australia and New Zealand: an evidence-based approach for establishing a first panel of chemistry analytes. Clin Biochem Rev 2014;35(4):213–35.Google Scholar
Tanaka, E, Inomata, S, Yasuhara, H. The clinical importance of conventional and quantitative liver function tests in liver transplantation. J Clin Pharm Ther 2000;25(6):411–19.Google Scholar
Teitelbaum, JE, Laskowski, A, Barrows, FP. Benign transient hyperphosphatasemia in infants and children: a prospective cohort. J Pediatr Endocrinol Metab 2011;24(5–6):351–3.CrossRefGoogle ScholarPubMed
Trauner, M, Fuchs, CD, Halilbasic, E, Paumgartner, G. New therapeutic concepts in bile acid transport and signaling for management of cholestasis. Hepatology 2017;65(4):1393–1404. doi:10.1002/hep.28991CrossRefGoogle ScholarPubMed
Tripodi, A, Primignani, M, Mannucci, PM, Caldwell, SH. Changing concepts of cirrhotic coagulopathy. Am J Gastroenterol 2017;112(2):274–81. doi:10.1038/ajg.2016.498CrossRefGoogle ScholarPubMed
van der Woerd, WL, van Mil, SW, Stapelbroek, JM, Klomp, LW, van de Graaf, SF, Houwen, RH. Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy. Best Pract Res Clin Gastroenterol 2010;24(5):541–53.CrossRefGoogle ScholarPubMed
Vos, MB, Abrams, SH, Barlow, SE, Caprio, S, Daniels, SR, Kohli, R, Xanthakos, SA. NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Non-alcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr 2017;64(2):319–34. doi:10.1097/mpg.0000000000001482Google Scholar
Wagner, M, Zollner, G, Trauner, M. New molecular insights into the mechanisms of cholestasis. J Hepatol 2009;51(3):565–80.CrossRefGoogle ScholarPubMed
Weiss, JS, Gautam, A, Lauff, JJ, Sundberg, MW, Jatlow, P, Boyer, JL, Seligson, D. The clinical importance of a protein-bound fraction of serum bilirubin in patients with hyperbilirubinemia. N Engl J Med 1983;309(3):147–50. doi:10.1056/NEJM198307213090305Google Scholar
Wijdicks, EF. Hepatic encephalopathy. N Engl J Med 2016;375(17):1660–70. doi:10.1056/NEJMra1600561CrossRefGoogle ScholarPubMed
Zierk, J, Arzideh, F, Haeckel, R, Cario, H, Fruhwald, MC, Gross, HJ, Rauh, M. Pediatric reference intervals for alkaline phosphatase. Clin Chem Lab Med 2017;55(1):102–10. doi:10.1515/cclm-2016-0318Google Scholar

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