Chronically elevated levels of liver enzymes
Martin Janičko Orcid.org 1, Eduard Veseliny Orcid.org 1, Peter Jarčuška Orcid.org 1
+ Affiliation
Summary
The evaluation of increased plasmatic aspartate transaminase, alanine transaminase, γ-glutamyl transpeptidase, and alkaline phosphatase activities is fundamental to a differential diagnosis of liver disease. The correct interpretation of the results of tests for these activities demands much experience. The best option is to use the standardized guidelines to avoid overlooking important pathologies and performing unnecessary tests. Individual patients should be evaluated depending on the urgency of the situation, the timing of the elevation in liver enzymes, and other circumstances. This paper presents a simple recommendation about how to proceed when evaluating elevated liver enzyme levels with respect to evidence-based medicine.
Keywords
alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, liver diseases, liver tests, γ-glutamyl transferaseTo read this article in full, please register for free on this website.
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Literature
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29. Dawson DA, Grant BF, Stinson FS et al. Effectiveness of the derived alcohol use disorders identification test (AUDIT-C) in screening for alcohol use disorders and risk drinking in the US general population. Alcohol Clin Exp Res 2005; 29 (5): 844–854.
30. Hafkenscheid JC, Dijt CC. Determination of serum aminotransferases: activation by pyridoxal-5’-phosphate in relation to substrate concentration. Clin Chem 1979; 25 (1): 55–59.
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33. Hansson P, Caron M, Johnson G et al. Blood phosphatidylethanol as a marker of alcohol abuse: levels in alcoholic males during withdrawal. Alcohol Clin Exp Res 1997; 21 (1): 108–110.
34. Cacoub P, Poynard T, Ghillani P et al. Extrahepatic manifestations of chronic hepatitis C. Arthritis Rheum 1999; 42 (10): 2204–2212.
35. Cacoub P, Gragnani L, Comarmond C. Extrahepatic manifestations of chronic hepatitis C virus infection. Dig Liver Dis 2014; 46 (Suppl 5): S165–S173. doi: 10.1016/j.dld.2014.10.005.
36. Han SH. Extrahepatic manifestations of chronic hepatitis B. Clin Liver Dis 2004; 8 (2): 403–418.
37. Tan EM, Feltkamp TE, Smolen JS et al. Range of antinuclear antibodies in „healthy“ individuals. Arthritis Rheum 1997; 40 (9): 1601–1611.
38. Hennes EM, Zeniya M, Czaja AJ et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008; 48 (1): 169–176. doi: 10.1002/hep.22322.
39. Heathcote EJ. Diagnosis and management of cholestatic liver disease. Clin Gastroenterol Hepatol 2007; 5 (7): 776–782.
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41. Padda MS, Sanchez M, Akhtar AJ et al. Drug-induced cholestasis. Hepatology 2011; 53 (4): 1377–1387. doi: 10.1002/ hep.24229.
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43. Flores A, Mayo MJ. Primary biliary cirrhosis in 2014. Curr Opin Gastroenterol 2014; 30 (3): 245–252. doi: 10.1097/ MOG. 0000000000000058.
2. Limdi JK, Hyde GM. Evaluation of abnormal liver function tests. Postgrad Med J 2003; 79 (932): 307–312.
3. Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med 2000; 342 (17): 1266–1271.
4. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ 2005; 172 (3): 367–379.
5. Fernandez NJ, Kidney BA. Alkaline phosphatase: beyond the liver. Vet Clin Pathol 2007; 36 (3): 223–233.
6. Kabir A, Pourshams A, Khoshnia M et al. Normal limit for serum alanine aminotransferase level and distribution of metabolic factors in old population of Kalaleh, Iran. Hepat Mon 2013; 13 (10): e10640. doi: 10.5812/hepatmon.10640.
7. Janičko M, Veselíny E, Orenčák R et al. Redefining the alanine aminotransferase upper limit of normal improves the prediction of metabolic syndrome risk. Eur J Gastroenterol Hepatol 2015; 27 (4): 405–411. doi: 10.1097/MEG.0000000000000297.
8. Pacifico L, Ferraro F, Bonci E et al. Upper limit of normal for alanine aminotransferase: quo vadis? Clin Chim Acta 2013; 422: 29–39. doi: 10.1016/j.cca.2013.03.030.
9. Lawrence S, Friedman L. Approach to the patient with abnormal liver biochemical and function tests. [online]. Available from: www.uptodate.com/contents/approach-to-the-patient-with-abnormal-liver-biochemical-and-function-tests.
10. Ioannou GN, Boyko EJ, Lee SP. The prevalence and predictors of elevated serum aminotransferase activity in the United States in 1999–2002. Am J Gastroenterol 2006; 101 (1): 76–82.
11. Chen CH, Huang MH, Yang JC et al. Prevalence and etiology of elevated serum alanine aminotransferase level in an adult population in Taiwan. J Gastroenterol Hepatol 2007; 22 (9): 1482–1489.
12. Papatheodoridis GV, Goulis J, Christodoulou D et al. High prevalence of elevated liver enzymes in blood donors: associations with male gender and central adiposity. Eur J Gastroenterol Hepatol 2007; 19 (1): 281–287.
13. Pourshams A, Malekzadeh R, Monavvari A et al. Prevalence and etiology of persistently elevated alanine aminotransferase levels in healthy Iranian blood donors. J Gastroenterol Hepatol 2005; 20 (2): 229–233.
14. Rác M, Fikselová M, Pecháčová K. Tuková choroba pečene ako príčina hepatocelulárneho karcinómu. Trendy v hepatológii 2015; 7 (1): 28–29. [online]. Dostupné z: www.hepatology.sk/trendy/trendy_hepa_01-2015_sec.pdf.
15. Morisco F, Stroffolini T, Mele A et al. Etiology of and risk factors for transient and persistent aminotransferase elevation in a population of virus-free blood donors: a multicentre study. Dig Liver Dis 2010; 42 (6): 441–445. doi: 10.1016/j.dld.2009.06.017.
16. Torezan–Filho MA, Alves VA, Neto CA et al. Clinical significance of elevated alanine aminotransferase in blood donors: a follow-up study. Liver Int 2004; 24 (6): 575–581.
17. Katkov WN, Friedman LS, Cody H et al. Elevated serum alanine aminotransferase levels in blood donors: the contribution of hepatitis C virus. Ann Intern Med 1991; 115 (11): 882–884.
18. Rozen P, Korn RJ, Zimmerman HJ. Computer analysis of liver function tests and their interrelationships in 347 cases of viral hepatitis. Isr J Med Sci 1970; 6 (1): 67–79.
19. Dufour DR, Lott JA, Nolte FS et al. Diag- nosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests. Clin Chem 2000; 46 (12): 2027–2049.
20. Bailey B, Amre DK, Gaudreault P. Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation. Crit Care Med 2003; 31 (1): 299–305.
21. Aragon G, Younossi ZM. When and how to evaluate mildly elevated liver enzymes in apparently healthy patients. Cleve Clin J Med 2010; 77 (3): 195–204. doi: 10.3949/ccjm.77a.09064.
22. Ostapowicz G, Fontana RJ, Schiødt FV et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002; 137 (12): 947–954.
23. Fogden E, Neuberger J. Alternative medicines and the liver. Liver Int 2003; 23 (4): 213–220.
24. Bellentani S, Saccoccio G, Costa G et al. Drinking habits as cofactors of risk for alcohol induced liver damage. The Dionysos Study Group. Gut 1997; 41 (6): 845–850.
25. Niederau C, Lange S, Fruhauf M et al. Cutaneous signs of liver disease: value for prognosis of severe fibrosis and cirrhosis. Liver Int 2008; 28 (5): 659–666. doi: 10.1111/j.1478-3231.2008.01694.x.
26. Dvořák K. Možnosti neinvazivní diagnostiky u NAFLD. Gastroent Hepatol 2015; 69 (2): 110–115.
27. Romero-Corral A, Somers VK, Sierra-Johnson J et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes (Lond) 2008; 32 (6): 959–966. doi: 10.1038/ijo.2008.11.
28. Jarčuška P, Janičko M, Dražilová S et al. Gamma-glutamyl transpeptidase level associated with metabolic syndrome and proinflammatory parameters in the young Roma population in eastern Slovakia: a population based study. Cent Eur J Public Health 2014; 22 (Suppl): S43–S50.
29. Dawson DA, Grant BF, Stinson FS et al. Effectiveness of the derived alcohol use disorders identification test (AUDIT-C) in screening for alcohol use disorders and risk drinking in the US general population. Alcohol Clin Exp Res 2005; 29 (5): 844–854.
30. Hafkenscheid JC, Dijt CC. Determination of serum aminotransferases: activation by pyridoxal-5’-phosphate in relation to substrate concentration. Clin Chem 1979; 25 (1): 55–59.
31. Golka K, Wiese A. Carbohydrate-deficient transferrin (CDT) – a biomarker for long-term alcohol consumption. J Toxicol Environ Health B Crit Rev 2004; 7 (4): 319–337.
32. Jatlow PI, Agro A, Wu R et al. Ethyl glucuronide and ethyl sulfate assays in clinical trials, interpretation, and limitations: results of a dose ranging alcohol challenge study and 2 clinical trials. Alcohol Clin Exp Res 2014; 38 (7): 2056–2065. doi: 10.1111/ acer.12407.
33. Hansson P, Caron M, Johnson G et al. Blood phosphatidylethanol as a marker of alcohol abuse: levels in alcoholic males during withdrawal. Alcohol Clin Exp Res 1997; 21 (1): 108–110.
34. Cacoub P, Poynard T, Ghillani P et al. Extrahepatic manifestations of chronic hepatitis C. Arthritis Rheum 1999; 42 (10): 2204–2212.
35. Cacoub P, Gragnani L, Comarmond C. Extrahepatic manifestations of chronic hepatitis C virus infection. Dig Liver Dis 2014; 46 (Suppl 5): S165–S173. doi: 10.1016/j.dld.2014.10.005.
36. Han SH. Extrahepatic manifestations of chronic hepatitis B. Clin Liver Dis 2004; 8 (2): 403–418.
37. Tan EM, Feltkamp TE, Smolen JS et al. Range of antinuclear antibodies in „healthy“ individuals. Arthritis Rheum 1997; 40 (9): 1601–1611.
38. Hennes EM, Zeniya M, Czaja AJ et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008; 48 (1): 169–176. doi: 10.1002/hep.22322.
39. Heathcote EJ. Diagnosis and management of cholestatic liver disease. Clin Gastroenterol Hepatol 2007; 5 (7): 776–782.
40. Poupon R, Chopra S. Pruritus associated with cholestasis. [online]. Available from: www.uptodate.com/contents/pruritus-associated-with-cholestasis.
41. Padda MS, Sanchez M, Akhtar AJ et al. Drug-induced cholestasis. Hepatology 2011; 53 (4): 1377–1387. doi: 10.1002/ hep.24229.
42. Matějková P, Drastich P, Jungwir- thová A. Primární sklerozující cholangoitida u pacientů s idiopatickými střevními záněty. Gastroent Hepatol 2012; 66 (3): 210–213.
43. Flores A, Mayo MJ. Primary biliary cirrhosis in 2014. Curr Opin Gastroenterol 2014; 30 (3): 245–252. doi: 10.1097/ MOG. 0000000000000058.