Liver Disease Evaluation

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

  • Acute presentation of jaundice, suspicion of hepatitis
  • Evaluation of asymptomatic elevation of transaminases

Laboratory Testing

  • Initial screening for suspected liver disease should include aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin
    • Recommend repeat serum testing prior to initiation of exhaustive evaluation of modestly elevated liver function tests (<2x upper reference limit for AST, ALT, ALP)
  • Further testing based on results from initial screening
    • Consider – PT, albumin, HCV antibodies, HBsAgHAV IgM, CBC, iron, total iron binding capacity and ferritin
    • If patient has suspected chronic disease, consider noninvasive testing for fibrosis (cirrhosis)
  • Patterns of elevation may suggest where abnormality exists
    • AST/ALT elevations – hepatocellular damage
    • ALP, bilirubin elevations – cholestasis
  • Elevated ALT, AST, gamma glutamyl transferase (GGT) and 5’ nucleotidase (5’ NT)
    • Combined elevation highly suggestive of liver disease
  • AST, ALT
    • Modest elevation – <10x upper reference limit (URL); seen in many types of liver disorders
      • Alcoholism
      • Gallstone-induced
      • Metabolic diseases
      • Acute and chronic hepatitis
    • Striking elevation (<20x URL)
    • AST/ALT ratios
      • Normal – 0.8-1.0
      • Alcoholic liver disease – >2.0
  • ALP
    • Up to 3-fold elevation may be seen in liver disease – not specific for cholestasis
    • Multiple isoenzymes – liver, bone, intestinal, placental
    • Elevation of ALP exclusive of other enzymes may indicate bone disease
      • ALP isoenzyme testing – differentiates between bone and liver as source of ALP elevation
      • GGT/5’ NT – distinguish elevated ALP as liver-related
        • Elevated GGT/5’ NT – liver
        • Normal GGT/5’ NT – bone
    • Isolated elevation of the liver isoenzyme is suspicious for early cholestasis but may also reflect tumor or granulomatous disease (eg, M. tuberculosissarcoidosis)
    • Level of elevation is not helpful in distinguishing intrahepatic from extrahepatic causes of cholestasis
  • Total bilirubin 
    • Elevated unconjugated (indirect) bilirubin – rarely reflects liver disease; commonly found in hemolytic disease
    • Elevated conjugated (direct) bilirubin – reflects hepatobiliary disease
    • Elevated delta bilirubin – reflects hepatobiliary disease and remains elevated longer than other bilirubin fractions during the convalescent phase of liver disease
    • Urine bilirubin – water-soluble conjugated fraction that implies hepatobiliary disease


  • Liver biopsy – gold standard for evaluation of fibrosis

Differential Diagnosis

Liver disease diagnosis can generally be made using a carefully obtained history, physical examination, and a few laboratory tests.


  • Prevalence – chronic liver disease is the 12th most common cause of death in U.S.
  • Age – incidence of chronic disease increases with age
  • Sex – M>F


  • Biochemical tests of liver function
    • May be normal in the presence of liver disease
    • Do not suggest a specific disease or accurately assess degree of liver function
    • Do suggest a category of liver disease (eg, cholestatic versus hepatocellular patterns) and are best ordered as groups of tests
      • Order as groups of tests for better categorization

Clinical Presentation

  • Liver disease
    • Acute
      • Generally hepatitis – may be any etiology
      • Fever, anorexia, fatigue, jaundice
      • Fulminant failure – encephalopathy, coagulopathy
    • Chronic
      • Frequently asymptomatic until late stage of disease (up to 40% of patients with cirrhosis)
      • Constitutional – fatigue, weight loss, anorexia
      • Late stage – ascites, spider angiomata, jaundice, pedal edema, esophageal varices, splenomegaly, encephalopathy

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Prothrombin Time 0030215
Method: Electromagnetic Mechanical Clot Detection


PT is not sensitive to mild/moderate decreases in factor activity

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Gamma Glutamyl Transferase, Serum or Plasma 0020009
Method: Quantitative Enzymatic

5'Nucleotidase 0080235
Method: Quantitative Enzymatic

Follow Up

If 5' NT is normal but ALP is elevated, perform bone-specific ALP testing

Hepatitis C Virus Antibody by CIA 2002483
Method: Qualitative Chemiluminescent Immunoassay

Follow Up

Positive results require confirmation by molecular testing (eg, Hepatitis C Virus by quantitative PCR or Hepatitis C Virus by quantitative PCR with reflex to HCV genotype by sequencing 

Hepatitis Panel, Acute with Reflex to HBsAg Confirmation 0020457
Method: Qualitative Chemiluminescent Immunoassay

Additional Tests Available

Iron and Iron Binding Capacity 0020420
Method: Quantitative Spectrophotometry


Aids in the diagnosis of iron deficiency, anemia, and iron overload

Ferritin 0070065
Method: Quantitative Chemiluminescent Immunoassay


Aids in the diagnosis of iron deficiency anemia and iron overload

Monitor treatment of hemochromatosis

Aspartate Aminotransferase, Serum or Plasma 0020007
Method: Quantitative Enzymatic

Alanine Aminotransferase, Serum or Plasma 0020008
Method: Quantitative Enzymatic

Alkaline Phosphatase, Serum or Plasma 0020005
Method: Quantitative Enzymatic

Bilirubin, Direct and Total, Serum or Plasma 0020426
Method: Quantitative Spectrophotometry

Alkaline Phosphatase Isoenzymes, Serum or Plasma 0021020
Method: Quantitative Heat Inactivation/Enzymatic

Bone Specific Alkaline Phosphatase 0070053
Method: Quantitative Chemiluminescent Immunoassay

Bilirubin, Total, Body Fluid 0020510
Method: Quantitative Spectrophotometry


For information on body fluid reference ranges and/or interpretive guidance visit

Bilirubin, Direct, Serum or Plasma 0020033
Method: Quantitative Spectrophotometry

Bilirubin, Total, Serum or Plasma 0020032
Method: Spectrophotometry

Albumin by Nephelometry 0050671
Method: Quantitative Nephelometry

Albumin, Serum or Plasma by Spectrophotometry 0020030
Method: Quantitative Spectrophotometry

Inhibitor Assay, PT with Reflex to PT 1:1 Mix 2003260
Method: Electromagnetic Mechanical Clot Detection


Initial screen for inhibitor in plasma

Reflex pattern – if the PT is prolonged, a PT 1:1 mix will be added

Ammonia, Plasma 0020043
Method: Colorimetry

Lactate Dehydrogenase, Isoenzymes 0020413
Method: Quantitative Enzymatic/Electrophoresis

Retinol Binding Protein 0050467
Method: Quantitative Nephelometry

Alpha-1-Antitrypsin 0050001
Method: Quantitative Immunoturbidimetry


Only determines AAT plasma concentration

Sex Hormone Binding Globulin 0099375
Method: Quantitative Electrochemiluminescent Immunoassay

General References

Aragon G, Younossi Z. When and how to evaluate mildly elevated liver enzymes in apparently healthy patients. Cleve Clin J Med. 2010; 77(3): 195-204. PubMed

Chou R, Wasson N. Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection: a systematic review. Ann Intern Med. 2013; 158(11): 807-20. PubMed

Hartwell J, Schwartz J. Evaluation and Management of Abnormal Liver Chemistry Tests in the Asymptomatic Outpatient. Case Study and Commentary, 16(11): 525-534. Journal of Clinical Outcomes Management/Turner White Communications Inc.. Wayne, PA [Accessed: Nov 2015]

Oh R, Hustead T. Causes and evaluation of mildly elevated liver transaminase levels. Am Fam Physician. 2011; 84(9): 1003-8. PubMed

Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology. 2008; 245(3): 194-205. PubMed

Plebani M, Basso D. Non-invasive assessment of chronic liver and gastric diseases. Clin Chim Acta. 2007; 381(1): 39-49. PubMed

Woreta T, Alqahtani S. Evaluation of abnormal liver tests. Med Clin North Am. 2014; 98(1): 1-16. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Akerley W, Boucher K, Bentz J, Arbogast K, Walters T. A phase II study of erlotinib as initial treatment for patients with stage IIIB-IV non-small cell lung cancer. J Thorac Oncol. 2009; 4(2): 214-9. PubMed

Medical Reviewers

Last Update: December 2015