ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries

American Journal of Gastroenterology

Volumn 112, Issue 1, 2017, Pages 18-35

  Kwo, Paul Y ^a   Cohen, Stanley M ^b   Lim, Joseph K ^c  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY HOSPITALS OF CLEVELAND   (United States)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; BILIRUBIN GLUCURONIDE; NON PRESCRIPTION DRUG;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALCOHOL LIVER DISEASE; ALKALINE PHOSPHATASE BLOOD LEVEL; ALPHA 1 ANTITRYPSIN DEFICIENCY; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; AUTOIMMUNE HEPATITIS; BILIRUBIN BLOOD LEVEL; CHEMICAL ANALYSIS; CHOLESTASIS; HEMOCHROMATOSIS; HEPATITIS A; HEPATITIS B; HEPATITIS C; HUMAN; LIVER BIOPSY; LIVER CELL DAMAGE; LIVER EXAMINATION; MORTALITY; NONALCOHOLIC FATTY LIVER; PRACTICE GUIDELINE; PRIMARY SCLEROSING CHOLANGITIS; PRIORITY JOURNAL; REVIEW; SCREENING; WILSON DISEASE; ALPHA 1-ANTITRYPSIN DEFICIENCY; BIOPSY; BLOOD; CHEMICAL AND DRUG INDUCED LIVER INJURY; HEPATITIS, AUTOIMMUNE; HEPATITIS, VIRAL, HUMAN; HEPATOLENTICULAR DEGENERATION; LIVER; LIVER DISEASES; LIVER DISEASES, ALCOHOLIC; METABOLISM; NON-ALCOHOLIC FATTY LIVER DISEASE; PATHOLOGY;

ALANINE TRANSAMINASE; ALKALINE PHOSPHATASE; ALPHA 1-ANTITRYPSIN DEFICIENCY; ASPARTATE AMINOTRANSFERASES; BILIRUBIN; BIOPSY; CHEMICAL AND DRUG INDUCED LIVER INJURY; CHOLESTASIS; HEMOCHROMATOSIS; HEPATITIS, AUTOIMMUNE; HEPATITIS, VIRAL, HUMAN; HEPATOLENTICULAR DEGENERATION; HUMANS; LIVER; LIVER DISEASES; LIVER DISEASES, ALCOHOLIC; NON-ALCOHOLIC FATTY LIVER DISEASE;

EID: 85006713734     PISSN: 00029270     EISSN: 15720241     Source Type: Journal    
DOI: 10.1038/ajg.2016.517     Document Type: Review

References (99)

1. Guyatt GH, Oxman AD, Vist GE et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. Br Med J 2008; 336: 924-6.
2. Helmke S, Colmenero J, Everson GT. Noninvasive assessment of liver function . Curr Opin Gastroenterol 2015; 31: 199-208.
3. Karmen A, Wroblewski F, Ladue JS. Transaminase activity in human blood. J Clin Invest 1955; 34: 126.
4. Price C, Albert K. Biochemical Assessment of Liver Function. Liver and Biliary Diseases-Pathophysiology, Diagnosis, Management. W.B. Saunders: London, 1979.
5. Dufour DR, Lott JA, Nolte FS et al. Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests. Clin Chem 2000; 46: 2027-49.
6. Dufour DR, Lott JA, Nolte FS et al. Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory tests in screening, diagnosis, and monitoring. Clin Chem 2000; 46: 2050-68.
7. Roberts WM. Variations in the phosphatase activity of the blood in disease. Br J Exp Pathol 1930; 11: 90-5.
8. Matsushita M, Komoda T. Relationship between the eff ects of a high-fat meal and blood group in determination of alkaline phosphatase activity. Rinsho Byori 2011; 59: 923-9.
9. Vroon DH, Israili Z. Alkaline phosphatase and gamma glutamyltransferase. In: Walker HK, Hall WD, Hurst JW (eds). Clinical Methods: The History, Physical, and Laboratory Examinations. Butterworths: Boston, 1990.
10. Wolf PL. Clinical signifi cance of an increased or decreased serum alkaline phosphatase level. Arch Pathol Lab Med 1978; 102: 497-501.
11. Kaplan MM. Alkaline phosphatase. N Engl J Med 1972; 286: 200-2.
12. Scharschmidt B, Blanckaert N, Farina F et al. Measurement of serum bilirubin and its mono-and diconjugates: application to patients with hepatobiliary disease. Gut 1982; 23: 643-9.
13. Neuschwander-Tetri BA, A. Unalp MH. Creer and Nonalcoholic Steatohepatitis Clinical Research Network. Influence of local reference populations on upper limits of normal for serum alanine aminotransferase levels. Arch Intern Med 2008; 168: 663-6.
14. Dutta A, Saha C, Johnson CS et al. Variability in the upper limit of normal for serum alanine aminotransferase levels: a statewide study. Hepatology 2009; 50: 1957-62.
15. Ceriotti F, Henny J, Queralto J et al. Common reference intervals for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ -glutamyl transferase (GGT) in serum: results from an IFCC multicenter study. Clin Chem Lab Med 2010; 48: 1593-601.
16. Nomura F, Ohnishi K, Satomura Y et al. Liver function in moderate obesity-study in 534 moderately obese subjects among 4613 male company employees. Int J Obes 1986; 10: 349-54.
17. Wejstal R, Hansson G, Lindholm A et al. Persistent alanine aminotransferase elevation in healthy Swedish blood donors-mainly caused by obesity. Vox Sang 1988; 55: 152-6.
18. Piton A, Poynard T, Imbert-Bismut F et al. Factors associated with serum alanine transaminase activity in healthy subjects: consequences for the defi-nition of normal values, for selection of blood donors, and for patients with chronic hepatitis C. MULTIVIRC Group. Hepatology 1998; 27: 1213-9.
19. Kim W, Flamm SL, Di Bisceglie AM et al. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology 2008; 47: 1363-70.
20. Green RM, Flamm S. AGA technical review on the evaluation of liver chemistry tests. Gastroenterology 2002; 123: 1367-84.
21. Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med 2000; 342: 1266-71.
22. Chalasani NP, Hayashi PH, Bonkovsky HL et al. ACG clinical guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol 2014; 109: 950-66.
23. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009; 50: 661-2.
24. 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.
25. Lee JK, Shim JH, Lee HC et al. Estimation of the healthy upper limits for serum alanine aminotransferase in Asian populations with normal liver histology. Hepatology 2010; 51: 1577-83.
26. Ruhl CE, Everhart JE. Upper limits of normal for alanine aminotransferase activity in the United States population. Hepatology 2012; 55: 447-54.
27. Arndt V, Brenner H, Rothenbacher D et al. Elevated liver enzyme activity in construction workers: prevalence and impact on early retirement and allcause mortality. Int Arch Occup Environ Health 1998; 71: 405-12.
28. Kim HC, Nam CM, Jee SH et al. Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study. Br Med J 2004; 328: 983.
29. Lee TH, Kim WR, Benson JT et al. Serum aminotransferase activity and mortality risk in a United States community. Hepatology 2008; 47: 880-7.
30. Ruhl CE, Everhart JE. Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology 2009; 136 (477-85): e11.
31. Ioannou GN, Weiss NS, Boyko EJ et al. Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the United States. Hepatology 2006; 43: 1145-51.
32. 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: 76-82.
33. Kaplan MM. Alanine aminotransferase levels: What's normal? Ann Intern Med 2002; 137: 49-51.
34. Wright C, Rivera JC, Baetz JH. Liver function testing in a working population: three strategies to reduce false-positive results. J Occup Environ Med 1988; 30: 693-7.
35. Nutt AK, Hassan HA, Lindsey J et al. Liver biopsy in the evaluation of patients with chronic hepatitis C who have repeatedly normal or near-normal serum alanine aminotransferase levels. Am J Med 2000; 109: 62-4.
36. Zeuzem S, Diago M, Gane E et al. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. Gastroenterology 2004; 127: 1724-32.
37. Niederau C, Fischer R, Purschel A et al. Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 1996; 110: 1107-19.
38. Browning JD, Szczepaniak LS, Dobbins R et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40: 1387-95.
39. Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 2003; 98: 960-7.
40. Wejstal R, Hansson G, Lindholm A et al. Persistent alanine aminotransferase elevation in healthy Swedish blood donors-mainly caused by obesity. Vox Sang 1988; 55: 152-6.
41. Rein DB, Smith BD, Wittenborn JS et al. The cost-effectiveness of birthcohort screening for hepatitis C antibody in U.S. primary care settings. Ann Intern Med 2012; 156: 263-70.
42. Smith BD, Morgan RL, Beckett GA et al. Recommendations for the identifi cation of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep 2012; 61: 1-32.
43. Alter MJ, Kuhnert WL, Finelli L. Guidelines for laboratory testing and result reporting of antibody to hepatitis C virus. Centers for Disease Control and Prevention. MMWR Recomm Rep 2003; 52: 1-13. 15; quiz CE1-4.
44. Kamal SM. Acute hepatitis C: a systematic review. Am J Gastroenterol 2008; 103: 1283-97; quiz 1298.
45. Weinbaum CM, Williams I, Mast EE et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep 2008; 57: 1-20.
46. Chalasani N, Younossi Z, Lavine JE et al. The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55: 2005-23.
47. Sanyal AJ. AGA technical review on nonalcoholic fatty liver disease. Gastroenterology 2002; 123: 1705-25.
48. Tapper EB, Castera L, Afdhal NH. FibroScan (vibration-controlled transient elastography): where does it stand in the United States practice. Clin Gastroenterol Hepatol 2015; 13: 27-36.
49. Kawachi I, Robinson GM, Stace NH. A combination of raised serum AST:ALT ratio and erythrocyte mean cell volume level detects excessive alcohol consumption. N Z Med J 1990; 103: 145-8.
50. Nyblom H, Berggren U, Balldin J et al. High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy drinking. Alcohol Alcohol 2004; 39: 336-9.
51. O'Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Am J Gastroenterol 2010; 105: 14-32; quiz 33.
52. Vierling JM. Autoimmune hepatitis and overlap syndromes: diagnosis and management. Clin Gastroenterol Hepatol 2015; 13: 2088-108.
53. Bacon BR, Adams PC, Kowdley KV et al. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011; 54: 328-43.
54. Beutler E, Felitti VJ, Koziol JA et al. P enetrance of 845G-> A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet 2002; 359: 211-8.
55. Gurrin LC, Bertalli NA, Dalton GW et al. HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity. Hepatology 2009; 50: 94-101.
56. Roberts EA, Schilsky ML. A practice guideline on Wilson disease. Hepatology 2003; 37: 1475-92.
57. Carrell RW, Lomas DA. Alpha1-antitrypsin deficiency-a model for conformational diseases. N Engl J Med 2002; 346: 45-53.
58. Fairbanks KD, Tavill AS. Liver disease in alpha 1-antitrypsin deficiency: a review. Am J Gastroenterol 2008; 103: 2136-41; quiz 2142.
59. Regev A, Guaqueta C, Molina EG et al. Does the heterozygous state of alpha-1 antitrypsin deficiency have a role in chronic liver diseases? Interim results of a large case-control study. J Pediatr Gastroenterol Nutr 2006; 43: S30-5.
60. Bader T. The myth of statin-induced hepatotoxicity. Am J Gastroenterol 2010; 105: 978.
61. Lata S, Chudy B. Acute cholestatic hepatitis caused by simvastatine in a 67-year-old patient. Przegl Lek 2006; 63: 97-8.
62. Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol & Ther 2013; 37: 3-17.
63. Beuers U, Gershwin ME, Gish RG et al. Changing nomenclature for PBC: from 'cirrhosis' to 'cholangitis'. Gut 2015: p. gutjnl-2015-310593.
64. Lindor KD, Gershwin ME, Poupon R et al. Primary biliary cirrhosis. Hepatology 2009; 50: 291-308.
65. Lindor KD, Kowdley KV, Harrison ME. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol 2015; 110: 646-59; quiz 660.
66. Jungst C, Lammert F. Cholestatic liver disease. Dig Dis 2013; 31: 152-4.
67. Castillo NE, Vanga RR, Theethira TG et al. Prevalence of abnormal liver function tests in celiac disease and the effect of a gluten-free diet in the US population. Am J Gastroenterol 2015; 110: 1216-22.
68. Rubio-Tapia A, Hill ID, Kelly CP et al. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 2013; 108: 656-76; quiz 677.
69. Pettersson J, Hindorf U, Persson P et al. Muscular exercise can cause highly pathological liver function tests in healthy men. Br J Clin Pharmacol 2008; 65: 253-9.
70. KazakoffMA, Sinusas K, Macchia C. Liver function test abnormalities in early Lyme disease. Arch Fam Med 1993; 2: 409-13.
71. White DJ, Talarico J, Chang HG et al. Human babesiosis in New York State: Review of 139 hospitalized cases and analysis of prognostic factors. Arch Intern Med 1998; 158: 2149-54.
72. Nutt AK, Raufman J. Gastrointestinal and hepatic manifestations of human ehrlichiosis: 8 cases and a review of the literature. Dig Dis 1999; 17: 37-43.
73. Menon KV, Shah V, Kamath PS. The Budd-Chiari syndrome. N Engl J Med 2004; 350: 578-85.
74. Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol 2006; 44: S6-9.
75. Udell JA, Wang CS, Tinmouth J et al. Does this patient with liver disease have cirrhosis? JAMA 2012; 307: 832-42.
76. Peternel WW, Schaefer JW, SchiffL. Clinical evaluation of liver size and hepatic scintiscan. Am J Dig Dis 1966; 11: 346-50.
77. Rosenfield AT, Laufer I, Schneider PB. The significance of a palpable liver. A correlation of clinical and radioisotope studies. Am J Roentgenol Radium Ther Nucl Med 1974; 122: 313-7.
78. Naylor CD. The rational clinical examination. Physical examination of the liver. JAMA 1994; 271: 1859-65.
79. Wegmann T. Parotid hypertrophy and Dupuytren's contracture in liver cirrhosis. Munch Med Wochenschr 1960; 102: 1926-9.
80. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. Canad Med Assoc J 2005; 172: 367-79.
81. Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology 2012; 55: 965-7.
82. Cohen JA, Kaplan MM. The SGOT/SGPT ratio-an indicator of alcoholic liver disease. Dig Dis Sci 1979; 24: 835-8.
83. Correia JP, Alves PS, Camilo EA. SGOT-SGPT ratios. Dig Dis Sci 1981; 26: 284.
84. Sheth SG, Flamm SL, Gordon FD et al. AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection. Am J Gastroenterol 1998; 93: 44-8.
85. Rockey DC, Caldwell SH, Goodman ZD et al. Liver biopsy. Hepatology 2009; 49: 1017-44.
86. Kaplan MM. Alkaline phosphatase. N Engl J Med 1972; 286: 200-2.
87. Lieberman D, Phillips D. "Isolated" elevation of alkaline phosphatase: signifi cance in hospitalized patients. J Clin Gastroenterol 1990; 12: 415-9.
88. Moussavian SN, Becker RC, Piepmeyer JL et al. Serum gamma-glutamyl transpeptidase and chronic alcoholism. Influence of alcohol ingestion and liver disease. Dig Dis Sci 1985; 30: 211-4.
89. Lee DH, Silventoinen K, Hu G et al. Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and women. Eur Heart J 2006; 27: 2170-6.
90. Kim HW, Lee SH, Lee DH. Relationship of serum gamma-glutamyltransferase levels with pulmonary function and chronic obstructive pulmonary disease. Lung 2014; 192: 719-27.
91. Fraser A, Ebrahim S, Smith GD et al. A comparison of associations of alanine aminotransferase and gamma-glutamyltransferase with fasting glucose, fasting insulin, and glycated hemoglobin in women with and without diabetes. Hepatology 2007; 46: 158-65.
92. Keeffe EB, Sunderland MC, Gabourel JD. Serum gamma-glutamyl transpeptidase activity in patients receiving chronic phenytoin therapy. Dig Dis Sci 1986; 31: 1056-61.
93. Lum G, Gambino SR. Serum gamma-glutamyl transpeptidase activity as an indicator of disease of liver, pancreas, or bone. Clin Chem 1972; 18: 358-62.
94. Watson KJ, Gollan JL. Gilbert's syndrome. Baillieres Clin Gastroenterol 1989; 3: 337-55.
95. Levine RA, Klatskin G. Unconjugated hyperbilirubinemia in the absence of overt hemolysis: Importance of acquired disease as an etiologic factor in 366 adolescent and adult subjects. Am J Med 1964; 36: 541-52.
96. Chand N, Sanyal AJ. Sepsis-induced cholestasis. Hepatology 2007; 45: 230-41.
97. Kantrowitz PA, Jones WA, Greenberger NJ, Isselbacher KJ. Greenberger and K.J. Isselbacher, Severe postoperative hyperbilirubinemia simulating obstructive jaundice. N Engl J Med 1967; 276: 590-8.
98. Schmid M, Hefti ML, Gattiker R et al. Benign postoperative intrahepatic cholestasis. N Engl J Med 1965; 272: 545-50.
99. Erlinger S, Arias IM, Dhumeaux D. Inherited disorders of bilirubin transport and conjugation: new insights into molecular mechanisms and consequences. Gastroenterology 2014; 146: 1625-38.