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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:  05 March 2014

Vicky Lee Ng
Affiliation:
University of Toronto; Liver Transplant Program, Division of Gastroenterology, Hepatology and Nutrition, SickKids Transplant Centre, Hospital for Sick Children, Toronto, Ontario, Canada
Frederick J. Suchy
Affiliation:
University of Colorado Medical Center
Ronald J. Sokol
Affiliation:
University of Colorado Medical Center
William F. Balistreri
Affiliation:
University of Cincinnati College of Medicine
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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 involves a number of tests performed in clinical laboratories. Many of the most commonly utilized serum chemistry tests, such as the aminotransferase and alkaline phosphatase (AP) levels, are often referred to as liver function tests, 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, with the term liver function tests reserved for true measures of hepatocyte synthetic function such as serum albumin levels and the prothrombin time (PT) or international normalized ratio. Any single biochemical test provides limited information that must be placed in the context of the entire clinical and historical picture. Currently 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) make a prognosis 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.

The widespread availability and frequent use of serum chemistry tests in children have resulted in an increase in the number of both normal and abnormal liver chemistry test values that must be evaluated by physicians. However, some limitations of liver biochemical tests must be recognized. First, screening laboratory tests may lack sensitivity. That is, if a liver chemistry test is normal, it does not ensure that the patient is free of liver disease. Children with chronic liver disease can have normal serum aminotransferase levels. Second, these tests are not specific for liver dysfunction. For example, serum aminotransferases may be elevated in patients with a non-hepatic disorder such as a musculoskeletal condition or cardiomyopathy. Finally, liver chemistry tests rarely provide a specific diagnosis; rather, they suggest a general category of liver disorder. For example, abnormal liver biochemical tests do not distinguish viral hepatitis from autoimmune hepatitis, or delineate intrahepatic from extrahepatic etiologies of cholestasis.

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Publisher: Cambridge University Press
Print publication year: 2014

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References

Adams, PC, Arthur, MJ, Boyer, TD, et al. Screening in liver disease: report of an AASLD clinical workshop. Hepatology 2004;39:1204–1212.CrossRefGoogle ScholarPubMed
Rahmioglu, N, Andrew, T, Cherkas, L, et al. Epidemiology and genetic epidemiology of the liver function test proteins. PLOS One 2009;4:e4435.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Schwimmer, JB, Dunn, W, Norman, GJ, et al. SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology 2010;138:1357–1364.CrossRefGoogle ScholarPubMed
Iorio, R, Sepe, A, Giannattasio, A, Cirillo, F, Vegnente, A. Hypertransaminasemia in childhood as a marker of genetic liver disorders. J Gastroenterol 2005;40:820–826.CrossRefGoogle ScholarPubMed
Farre, C, Esteve, M, Curcoy, A, et al. Hypertransaminasemia in pediatric celiac disease patients and its prevalence as a diagnostic clue. Am J Gastroenterol 2002;97:3176–3181.CrossRefGoogle ScholarPubMed
Cohen, JC, Horton, JD, Hobbs, HH. Human fatty liver disease: old questions and new insights. Science 2011;332(6037):1519–1523.CrossRefGoogle ScholarPubMed
Mencin, AA, Lavine, JE. Nonalcoholic fatty liver disease in children. Curr Opin Clin Nutr Metab Care 2011;14:151–157.Google ScholarPubMed
Kamath, BM, Olthoff, KM. Liver transplantation in children: update 2010. Pediatr Clin North Am 2010;57:401–414.CrossRefGoogle ScholarPubMed
Keller, MS, Coln, CE, Trimble, JA, Green, MC, Weber, TR. The utility of routine trauma laboratories in pediatric trauma resuscitations. Am J Surg 2004;188:671–678.CrossRefGoogle ScholarPubMed
Kaplowitz, N. Drug-induced liver injury. Clin Infect Dis 2004;38(Suppl 2):S44–S48.CrossRefGoogle ScholarPubMed
Giannini, E, Risso, D, Botta, F, et al. Validity and clinical utility of the aspartate aminotransferase-alanine aminotransferase ratio in assessing disease severity and prognosis in patients with hepatitis C virus-related chronic liver disease. Arch Intern Med 2003;163:218–224.CrossRefGoogle ScholarPubMed
Diehl, AM, Potter, J, Boitnott, J, et al. Relationship between pyridoxal 5′-phosphate deficiency and aminotransferase levels in alcoholic hepatitis. Gastroenterology 1984;86:632–636.Google ScholarPubMed
Rosenthal, P, Haight, M. Aminotransferase as a prognostic index in infants with liver disease. Clin Chem 1990;36:346–348.Google 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;100:1129–1134.CrossRefGoogle ScholarPubMed
Kaplan, MM. Alkaline phosphatase. Gastroenterology 1972;62:452–468.Google ScholarPubMed
Seetharam, S, Sussman, NL, Komoda, T, Alpers, DH. The mechanism of elevated alkaline phosphatase activity after bile duct ligation in the rat. Hepatology 1986;6:374–380.CrossRefGoogle ScholarPubMed
McEvoy, M, Skrabanek, P, Wright, E, Powell, D, McDonagh, B. Family with raised serum alkaline phosphatase activity in the absence of disease. BMJ (Clin Res Ed) 1981;282(6272):1272.CrossRefGoogle ScholarPubMed
Bamford, KF, Harris, H, Luffman, JE, Robson, EB, Cleghorn, TE. Serum-alkaline-phosphatase and the ABO blood-groups. Lancet 1965;i:530–531.CrossRefGoogle 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;23:927–930.CrossRefGoogle ScholarPubMed
Teitelbaum, JE, Laskowski, A, Barrows, FP. Benign transient hyperphosphatasemia in infants and children: a prospective cohort. J Pediatr Endocrinol Metab 2011;24(5–6):351–353.CrossRefGoogle ScholarPubMed
Chopra, S, Griffin, PH. Laboratory tests and diagnostic procedures in evaluation of liver disease. Am J Med 1985;79:221–230.CrossRefGoogle ScholarPubMed
Cabrera-Abreu, JC, Green, A. Gamma-glutamyltransferase: value of its measurement in paediatrics. Ann Clin Biochem 2002;39:22–25.CrossRefGoogle ScholarPubMed
Hospital for Sick Children Toronto, Canada. Reference Values and SI Unit Information. Toronto: Hospital for Sick Children, 1993.Google 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;5:542–548.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;12:21–26.CrossRefGoogle ScholarPubMed
van der Woerd, WL, van Mil, SW, Stapelbroek, JM, et al. Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy. Best Pract Res Clin Gastroenterol 2010;24:541–553.CrossRefGoogle ScholarPubMed
Wagner, M, Zollner, G, Trauner, M. New molecular insights into the mechanisms of cholestasis. J Hepatol 2009;51:565–580.CrossRefGoogle ScholarPubMed
Hill, PG, Sammons, HG. An assessment of 5′-nucleotidase as a liver-function test. Q J Med 1967;36(144):457–468.Google ScholarPubMed
Ahn, H, Li, CS, Wang, W. Sickle cell hepatopathy: clinical presentation, treatment, and outcome in pediatric and adult patients. Pediatr Blood Cancer 2005;45:184–190.CrossRefGoogle ScholarPubMed
Banks, BM, Pineda, EP, Goldbarg, JA, Rutenburg, AM. Clinical value of serum leucine aminopeptidase determinations. N Engl J Med 1960;263:1277–1281.CrossRefGoogle ScholarPubMed
Doumas, BT, Peters, T. Serum and urine albumin: a progress report on their measurement and clinical significance. Clin Chim Acta 1997;258:3–20.CrossRefGoogle ScholarPubMed
Tripodi, A, Mannucci, PM. The coagulopathy of chronic liver disease. N Engl J Med 2011;365:147–156.CrossRefGoogle ScholarPubMed
Lisman, T, Porte, RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010;116:878–885.CrossRefGoogle ScholarPubMed
Croffie, J, 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;103:675–678.CrossRefGoogle ScholarPubMed
Squires, RH, Shneider, BL, Bucuvalas, J, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr 2006;148:652–658.CrossRefGoogle ScholarPubMed
Andrew, M, Paes, B, Johnston, M. Development of the hemostatic system in the neonate and young infant. Am J Pediatr Hematol Oncol 1990;12:95–104.CrossRefGoogle ScholarPubMed
Andrew, M, Paes, B, Milner, R, et al. Development of the human coagulation system in the full-term infant. Blood 1987;70:165–172.Google ScholarPubMed
Andrew, M, Paes, B, Milner, R, et al. Development of the human coagulation system in the healthy premature infant. Blood 1988;72:1651–1657.Google ScholarPubMed
Dixon, JL, Ginsberg, HN. Hepatic synthesis of lipoproteins and apolipoproteins. Semin Liver Dis 1992;12:364–372.CrossRefGoogle ScholarPubMed
Miller, JP. Dyslipoproteinaemia of liver disease. Baillieres Clin Endocrinol Metab 1990;4:807–832.CrossRefGoogle ScholarPubMed
Seidel, D. Lipoproteins in liver disease. J Clin Chem Clin Biochem 1987;25:541–551.Google ScholarPubMed
Lontie, JF, Dubois, DY, Malmendier, CL, et al. Plasma lipids and apolipoproteins in end-stage liver disease. Clin Chim Acta 1990;195(1–2):93–96.CrossRefGoogle ScholarPubMed
Tukey, RH, Strassburg, CP. Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 2000;40:581–616.CrossRefGoogle ScholarPubMed
Mullenbach, R, Lammert, F. An update on genetic analysis of cholestatic liver diseases: digging deeper. Dig Dis 2011;29:72–77.CrossRefGoogle ScholarPubMed
Weiss, JS, Gautam, A, Lauff, JJ, et al. The clinical importance of a protein-bound fraction of serum bilirubin in patients with hyperbilirubinemia. N Engl J Med 1983;309:147–150.CrossRefGoogle ScholarPubMed
Davis, AR, Rosenthal, P, Escobar, GJ, Newman, TB. Interpreting conjugated bilirubin levels in newborns. J Pediatr 2011;158:562–565.CrossRefGoogle ScholarPubMed
Hirschfield, GM, Heathcote, EJ, Gershwin, ME. Pathogenesis of cholestatic liver disease and therapeutic approaches. Gastroenterology 2010;139:1481–1496.CrossRefGoogle ScholarPubMed
Benchimol, EI, Walsh, CM, Ling, SC. Early diagnosis of neonatal cholestatic jaundice: test at 2 weeks. Can Fam Physician 2009;55:1184–1192.Google ScholarPubMed
Davit-Spraul, A, Fabre, M, Branchereau, S, et al. ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC): phenotypic differences between PFIC1 and PFIC2 and natural history. Hepatology 2010;51:1645–1655.CrossRefGoogle ScholarPubMed
Pawlikowska, L, Strautnieks, S, Jankowska, I, et al. Differences in presentation and progression between severe FIC1 and BSEP deficiencies. J Hepatol 2010;53:170–178.CrossRefGoogle ScholarPubMed
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;7:669–681.CrossRefGoogle ScholarPubMed
Clayton, PT. Disorders of bile acid synthesis. J Inherit Metab Dis 2011;34:593–604.CrossRefGoogle ScholarPubMed
Wagner, M, Zollner, G, Trauner, M. Nuclear receptors in liver disease. Hepatology 2011;53:1023–1034.CrossRefGoogle ScholarPubMed
Setchell, KD, O’Connell, NC. Bile acid synthesis and metabolism. In Walker, W, Goulet, O, Kleiman, R, et al. (eds.) Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. Philadelphia, PA: Decker, 2004, pp. 1308–1343.Google Scholar
Setchell, KD, Heubi, JE. Defects in bile acid biosynthesis-diagnosis and treatment. J Pediatr Gastroenterol Nutr 2006;43(Suppl 1):S17–S22.CrossRefGoogle ScholarPubMed
Javitt, NB, Keating, JP, Grand, RJ, Harris, RC. Serum bile acid patterns in neonatal hepatitis and extrahepatic biliary atresia. J Pediatr 1977;90:736–739.CrossRefGoogle ScholarPubMed
Nemeth, A, Samuelson, K, Strandvik, B. Serum bile acids as markers of juvenile liver disease in alpha 1-antitrypsin deficiency. J Pediatr Gastroenterol Nutr 1982;1:479–483.CrossRefGoogle ScholarPubMed
Burra, P, Masier, A. Dynamic tests to study liver function. Eur Rev Med Pharmacol Sci 2004;8:19–21.Google ScholarPubMed
Orlando, R, Palatini, P. The effect of age on plasma MEGX concentrations. Br J Clin Pharmacol 1997;44:206–208.CrossRefGoogle ScholarPubMed
Tanaka, E, Inomata, S, Yasuhara, H. The clinical importance of conventional and quantitative liver function tests in liver transplantation. J Clin Pharm Ther 2000;25:411–419.CrossRefGoogle ScholarPubMed
Lebel, S, Nakamachi, Y, Hemming, A, et al. 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;36:62–71.CrossRefGoogle ScholarPubMed
Bachmann, C. Mechanisms of hyperammonemia. Clin Chem Lab Med 2002;40:653–662.CrossRefGoogle ScholarPubMed
Furuya, KN, Durie, PR, Roberts, EA, et al. Glycine conjugation of para-aminobenzoic acid (PABA): a quantitative test of liver function. Clin Biochem 1995;28:531–540.CrossRefGoogle ScholarPubMed
Chambers, JC, Zhang, W, Sehmi, J, et al. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat Genet 2011;43:1131–1138.CrossRefGoogle ScholarPubMed

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