Approach to the patient with abnormal liver biochemical and function tests
- Lawrence S Friedman, MD
Lawrence S Friedman, MD
- Section Editor — General Gastroenterology
- Professor of Medicine
- Harvard Medical School
- Tufts University School of Medicine
- Section Editor
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — General Hepatology
- Section Editor — Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
Abnormal liver biochemical and function tests are frequently detected in asymptomatic patients since many screening blood test panels routinely include them . A population-based survey in the United States conducted between 1999 and 2002 estimated that an abnormal alanine aminotransferase (ALT) was present in 8.9 percent of respondents. Although the term "liver function tests" (LFTs) is used commonly, it is imprecise and potentially misleading since many of the tests reflecting the health of the liver are not direct measures of its function. Furthermore, the commonly used liver biochemical tests may be abnormal even in patients with a healthy liver. However, for the sake of simplicity, the abbreviation "LFTs" will be used in this discussion to denote liver biochemical and function tests in general.
This topic review will provide an overview on the evaluation of patients with abnormal liver biochemical and function tests. Detailed discussions of the individual tests are presented separately. (See "Liver biochemical tests that detect injury to hepatocytes" and "Enzymatic measures of cholestasis (eg, alkaline phosphatase, 5'-nucleotidase, gamma-glutamyl transpeptidase)" and "Classification and causes of jaundice or asymptomatic hyperbilirubinemia" and "Tests of the liver's biosynthetic capacity (eg, albumin, coagulation factors, prothrombin time)".)
COMMON LIVER BIOCHEMICAL AND FUNCTION TESTS
Blood tests commonly obtained to evaluate the health of the liver include liver enzyme levels, tests of hepatic synthetic function, and the serum bilirubin level. Elevations of liver enzymes often reflect damage to the liver or biliary obstruction, whereas an abnormal serum albumin or prothrombin time may be seen in the setting of impaired hepatic synthetic function. The serum bilirubin in part measures the liver's ability to detoxify metabolites and transport organic anions into bile.
Liver enzymes — Liver enzymes that are commonly measured in the serum include:
●Serum aminotransferases: alanine aminotransferase (ALT, formerly called SGPT) and aspartate aminotransferase (AST, formerly called SGOT)
- Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med 2000; 342:1266.
- Ruhl CE, Everhart JE. Upper limits of normal for alanine aminotransferase activity in the United States population. Hepatology 2012; 55:447.
- Ruhl CE, Everhart JE. Trunk fat is associated with increased serum levels of alanine aminotransferase in the United States. Gastroenterology 2010; 138:1346.
- Prati D, Taioli E, Zanella A, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 2002; 137:1.
- Piton A, Poynard T, Imbert-Bismut F, et al. Factors associated with serum alanine transaminase activity in healthy subjects: consequences for the definition of normal values, for selection of blood donors, and for patients with chronic hepatitis C. MULTIVIRC Group. Hepatology 1998; 27:1213.
- Kaplan MM. Alanine aminotransferase levels: what's normal? Ann Intern Med 2002; 137:49.
- Dutta A, Saha C, Johnson CS, Chalasani N. Variability in the upper limit of normal for serum alanine aminotransferase levels: a statewide study. Hepatology 2009; 50:1957.
- Nannipieri M, Gonzales C, Baldi S, et al. Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study. Diabetes Care 2005; 28:1757.
- Cabrera-Abreu JC, Green A. Gamma-glutamyltransferase: value of its measurement in paediatrics. Ann Clin Biochem 2002; 39:22.
- Marshall T, Williams J, Williams KM. Electrophoresis of serum isoenzymes and proteins following acute myocardial infarction. J Chromatogr 1991; 569:323.
- Smit MJ, Duursma AM, Bouma JM, Gruber M. Receptor-mediated endocytosis of lactate dehydrogenase M4 by liver macrophages: a mechanism for elimination of enzymes from plasma. Evidence for competition by creatine kinase MM, adenylate kinase, malate, and alcohol dehydrogenase. J Biol Chem 1987; 262:13020.
- http://mghlabtest.partners.org/MGH_Reference_Intervals_August_2011.pdf (Accessed on March 29, 2013).
- Liangpunsakul S, Chalasani N. What should we recommend to our patients with NAFLD regarding alcohol use? Am J Gastroenterol 2012; 107:976.
- Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 2012; 142:1592.
- Myers RP, Cerini R, Sayegh R, et al. Cardiac hepatopathy: clinical, hemodynamic, and histologic characteristics and correlations. Hepatology 2003; 37:393.
- 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.
- Cohen JA, Kaplan MM. The SGOT/SGPT ratio--an indicator of alcoholic liver disease. Dig Dis Sci 1979; 24:835.
- Gitlin N, Serio KM. Ischemic hepatitis: widening horizons. Am J Gastroenterol 1992; 87:831.
- Fuchs S, Bogomolski-Yahalom V, Paltiel O, Ackerman Z. Ischemic hepatitis: clinical and laboratory observations of 34 patients. J Clin Gastroenterol 1998; 26:183.
- Henrion J, Schapira M, Luwaert R, et al. Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases. Medicine (Baltimore) 2003; 82:392.
- Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007; 45:507.
- Dalton HR, Hunter JG, Bendall R. Autochthonous hepatitis E in developed countries and HEV/HIV coinfection. Semin Liver Dis 2013; 33:50.
- Scobie L, Dalton HR. Hepatitis E: source and route of infection, clinical manifestations and new developments. J Viral Hepat 2013; 20:1.
- Davern TJ, Chalasani N, Fontana RJ, et al. Acute hepatitis E infection accounts for some cases of suspected drug-induced liver injury. Gastroenterology 2011; 141:1665.
- Litin SC, O'Brien JF, Pruett S, et al. Macroenzyme as a cause of unexplained elevation of aspartate aminotransferase. Mayo Clin Proc 1987; 62:681.
- Daniel S, Ben-Menachem T, Vasudevan G, et al. Prospective evaluation of unexplained chronic liver transaminase abnormalities in asymptomatic and symptomatic patients. Am J Gastroenterol 1999; 94:3010.
- Skelly MM, James PD, Ryder SD. Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol 2001; 35:195.
- 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.
- Das A, Post AB. Should liver biopsy be done in asymptomatic patients with chronically elevated transaminases: A cost-utility analysis (abstract). Gastroenterology 1998; 114:A9.
- Sorbi D, McGill DB, Thistle JL, et al. An assessment of the role of liver biopsies in asymptomatic patients with chronic liver test abnormalities. Am J Gastroenterol 2000; 95:3206.
- Owen MC, Pike LS, George PM, et al. Macro-alkaline phosphatase due to IgG kappa complex: demonstration with polyethylene glycol precipitation and immunofixation. Ann Clin Biochem 2002; 39:523.
- Watson KJ, Gollan JL. Gilbert's syndrome. Baillieres Clin Gastroenterol 1989; 3:337.
- Halilbasic E, Claudel T, Trauner M. Bile acid transporters and regulatory nuclear receptors in the liver and beyond. J Hepatol 2013; 58:155.
- van de Steeg E, Stránecký V, Hartmannová H, et al. Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin Invest 2012; 122:519.
- COMMON LIVER BIOCHEMICAL AND FUNCTION TESTS
- Liver enzymes
- - Aminotransferases
- - Alkaline phosphatase
- - Gamma-glutamyl transpeptidase
- - 5'-nucleotidase
- - Lactate dehydrogenase
- Function tests
- Reference ranges
- INITIAL EVALUATION
- Physical examination
- Laboratory tests
- - Patterns of LFT abnormalities
- - AST to ALT ratio
- - Magnitude of AST and ALT elevations
- - Other laboratory abnormalities
- ELEVATED SERUM AMINOTRANSFERASES
- Acute liver failure
- Marked elevation without liver failure
- - Differential diagnosis
- - Evaluation of markedly elevated aminotransferases
- Mild to moderate elevation
- - Differential diagnosis
- - Evaluation of mildly or moderately elevated aminotransferases
- ELEVATED ALKALINE PHOSPHATASE
- Confirming an elevated alkaline phosphatase is of hepatic origin
- Differential diagnosis
- Evaluation of elevated alkaline phosphatase
- - Extrahepatic cholestasis
- - Intrahepatic cholestasis
- ISOLATED GAMMA-GLUTAMYL TRANSPEPTIDASE (GGT) ELEVATION
- ISOLATED HYPERBILIRUBINEMIA
- Unconjugated (indirect) hyperbilirubinemia
- - Hemolysis
- - Impaired hepatic uptake or conjugation
- Conjugated (direct) hyperbilirubinemia
- ISOLATED ABNORMALITIES OF TESTS OF SYNTHETIC FUNCTION
- WHEN TO REFER TO A SPECIALIST
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS