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

Indications for Testing

  • Assess presence of fibrosis in patients with known liver disease or newly discovered disease

Laboratory Testing

  • Serum testing (noninvasive)
    • Indirect markers
      • Main initial markers [aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet count, prothrombin time (PT)] are not useful on their own
      • Combining markers with noninvasive scans may improve sensitivity
    • Direct markers
      • Multiple biomarkers exist – most have relatively low specificity and sensitivity if used alone
        • Sensitivity and specificity based on disease process involved in fibrosis
        • No evidence to support use of collagen or metalloprotease measurements
      • Hyaluronic acid
        • Unsulfated, highly-polymerized glycosaminoglycan
        • Endogenous ligand for toll-like receptor of Kupffer cells
        • Synthesized by activated hepatic stellate cells
        • Most useful in nonalcoholic liver fibrosis
        • Negative predictive value is 93-99%
          • <55 µg/L excludes patients unlikely to have extensive fibrosis or cirrhosis
        • May avoid or postpone need for liver biopsy
        • Has been combined in panel testing with other markers in attempts to improve sensitivity (Fibrospect, HepaScore)


  • Liver biopsy (invasive)
    • Remains important in cases with diagnostic uncertainty with coexisting disorders (HIV and hepatitis C), overlapping syndromes (primary biliary cirrhosis and autoimmune hepatitis), when there is an absolute necessity for diagnosis
    • Considered gold standard for diagnosis of fibrosis
    • Recommended sample size – at least 15 mm long and containing >5 portal tracts
    • Limitations – costly, painful, subject to sampling error (identifies hepatic disease in only 65-75%), morbidity (0.3%), mortality (0.01%)


  • Ultrasound – may help in diagnosis of NAFLD
  • FibroScan – measures liver stiffness in kPa (vibration controlled transient elastography)
    • Generates mild-amplitude, low-frequency elastic waves in liver (50Hz)
      • Elastic waves travel faster through stiffer tissues (fibrotic or cirrhotic)
    • Has been evaluated for fibrosis and cirrhosis assessment in chronic HBV and HCV; HIV/HCV coinfection; nonalcoholic fatty liver disease; alcohol liver disease; and biliary diseases (eg, PBC, PSC)
    • Comparison of performance to indirect markers (eg, serology tests)
      • Studies demonstrate lower and higher sensitivity results
        • Even in studies demonstrating lower sensitivity, sensitivity is comparable to indirect markers
  • Magnetic resonance elastography
    • Same principal as FibroScan
  • Acoustic radiation force impulse
    • Evaluates localized tissue displacement from acoustic pulses using B-mode ultrasonography

Chronic liver disease is a common problem worldwide.


  • Prevalence
    • Chronic viral hepatitis (B or C) infection – leading cause of chronic liver disease, affects >4 million people in the U.S.
    • Alcohol-related liver disease results in >12,000 deaths annually in U.S.
  • Age – unusual in patients <40 years unless in combination with a genetic disease associated with cirrhosis
  • Sex – M>F



  • Chronic liver inflammation leads to an increase in interstitial fibrous tissue
  • Widespread disruption and secondary attempts at repair by the liver cause irreversible histologic changes leading to cirrhosis

Clinical Presentation

  • May be asymptomatic until late-stage disease
  • Hepatocellular dysfunction – jaundice, hepatomegaly
  • Portal hypertension – varices, splenomegaly, ascites, palmar erythema, spider angiomata

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

Hyaluronic Acid, Serum 0081138
Method: Quantitative Enzyme-Linked Immunosorbent Assay


Results obtained with different assay methods or kits cannot be used interchangeably

Fasting specimens best, as eating slightly increases hyaluronic acid (HA)

Follow Up

If elevated may need to perform liver biopsy

Liver Fibrosis, Chronic Viral Hepatitis (Echosens FibroMeter) 2005661
Method: Quantitative Nephelometry/Quantitative Enzymatic/Quantitative Spectrophotometry/Automated Cell Count/ Electromagnetic Mechanical Clot Detection


Results should be interpreted in conjunction with the patient’s clinical history, particularly when the rules-based system has modified the scores

Test is not validated for individuals <18 years

Additional Tests Available

Aspartate Aminotransferase, Serum or Plasma 0020007
Method: Quantitative Enzymatic


Indirect marker for liver fibrosis

Alanine Aminotransferase, Serum or Plasma 0020008
Method: Quantitative Enzymatic


Indirect marker for liver fibrosis

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


Indirect marker for liver fibrosis

Prothrombin Time 0030215
Method: Electromagnetic Mechanical Clot Detection


Indirect marker for liver fibrosis

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


Indirect marker for liver fibrosis

Alpha-2-Macroglobulin 0050005
Method: Quantitative Nephelometry


Indirect marker for liver fibrosis

Platelets 0040235
Method: Automated Cell Count


Indirect marker for liver fibrosis

Nonalcoholic steatohepatitis (NASH) FibroSURE 2008868
Method: Semi-Quantitative Immunologic/Colorimetry/Kinetic/Nephelometry


Estimate degree of liver fibrosis in individuals with nonalcoholic fatty liver disease (NAFLD)

Not recommended for individuals with other liver diseases due to potentially inaccurate quantitative predictions of fibrosis

Unacceptable conditions – specimens from patients under the age of 14

Haptoglobin 0050280
Method: Quantitative Immunoturbidimetry


Use to calculate indirect marker index

Cholesterol, Serum or Plasma 0020031
Method: Quantitative Enzymatic


Use to calculate indirect marker index

Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite), but only when concentrations are at or above those expected during acetaminophen overdose

General References

Adams L. Biomarkers of liver fibrosis. J Gastroenterol Hepatol. 2011; 26(5): 802-9. PubMed

Adebajo C, Talwalkar J, Poterucha J, Kim R, Charlton M. Ultrasound-based transient elastography for the detection of hepatic fibrosis in patients with recurrent hepatitis C virus after liver transplantation: a systematic review and meta-analysis. Liver Transpl. 2012; 18(3): 323-31. PubMed

Armutcu F, Akyol S, Ucar F, Erdogan S, Akyol O. Markers in nonalcoholic steatohepatitis. Adv Clin Chem. 2013; 61: 67-125. PubMed

Carey E, Carey W. Noninvasive tests for liver disease, fibrosis, and cirrhosis: Is liver biopsy obsolete? Cleve Clin J Med. 2010; 77(8): 519-27. PubMed

Castéra L, Le Bail B, Roudot-Thoraval F, Bernard P, Foucher J, Merrouche W, Couzigou P, de Lédinghen V. Early detection in routine clinical practice of cirrhosis and oesophageal varices in chronic hepatitis C: comparison of transient elastography (FibroScan) with standard laboratory tests and non-invasive scores. J Hepatol. 2009; 50(1): 59-68. PubMed

Chon Y, Choi E, Song K, Park J, Kim D, Han K, Chon C, Ahn S, Kim S. Performance of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B: a meta-analysis. PLoS One. 2012; 7(9): e44930. 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

Chrostek L, Panasiuk A. Liver fibrosis markers in alcoholic liver disease. World J Gastroenterol. 2014; 20(25): 8018-23. PubMed

Degos F, Perez P, Roche B, Mahmoudi A, Asselineau J, Voitot H, Bedossa P, FIBROSTIC study group. Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: a multicenter prospective study (the FIBROSTIC study). J Hepatol. 2010; 53(6): 1013-21. PubMed

Duarte-Rojo A, Altamirano J, Feld J.  Noninvasive markers of fibrosis: key concepts for improving accuracy in daily clinical practice. Ann Hepatol. 2012; 11(4): 426-39. PubMed

Foucher J, Chanteloup E, Vergniol J, Castéra L, Le Bail B, Adhoute X, Bertet J, Couzigou P, de Lédinghen V. Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut. 2006; 55(3): 403-8. PubMed

Lee M, Cheong J, Um S, Seo Y, Kim D, Hwang S, Yang J, Han K, Cho S. Comparison of surrogate serum markers and transient elastography (Fibroscan) for assessing cirrhosis in patients with chronic viral hepatitis. Dig Dis Sci. 2010; 55(12): 3552-60. PubMed

Martínez S, Crespo G, Navasa M, Forns X. Noninvasive assessment of liver fibrosis. Hepatology. 2011; 53(1): 325-35. PubMed

Nguyen-Khac E, Chatelain D, Tramier B, Decrombecque C, Robert B, Joly J, Brevet M, Grignon P, Lion S, Le Page L, Dupas J. Assessment of asymptomatic liver fibrosis in alcoholic patients using fibroscan: prospective comparison with seven non-invasive laboratory tests. Aliment Pharmacol Ther. 2008; 28(10): 1188-98. PubMed

Patel K, Shackel N. Current status of fibrosis markers. Curr Opin Gastroenterol. 2014; 30(3): 253-9. PubMed

Sebastiani G, Gkouvatsos K, Plebani M. Non-invasive assessment of liver fibrosis: it is time for laboratory medicine. Clin Chem Lab Med. 2011; 49(1): 13-32. PubMed

Medical Reviewers

Last Update: December 2015