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Liver Fibrosis Panel, HepaScore

  • Interpretive Guide
Liver Fibrosis Panel, HepaScore

Test Summary

Liver Fibrosis Panel, HepaScore®


Clinical Use

  • Predict extent of liver fibrosis in individuals infected with hepatitis C virus (HCV)

Clinical Background

Treatment of chronic HCV infection can prevent cirrhosis and reduce the likelihood of hepatocellular carcinoma (HCC).1 Not all patients are treated with antiviral therapy in the early days following onset since only 20% to 30% of untreated people will develop cirrhosis.1 Treatment decisions are based in part on the stage of liver fibrosis, which marks the progression to cirrhosis. Individuals with minimal fibrosis (ie, F0 or F1 on the METAVIR scoring system) are not likely to develop advanced fibrosis in the short-term, even in light of long-standing disease, and are typically monitored every 3 to 5 years.1 Individuals with significant fibrosis, ie, METAVIR score F2, are at increased risk of developing cirrhosis and are usually treated.1

The gold standard for determining the extent of fibrosis is liver biopsy.2 However, the procedure carries a moderate risk of complications, including bleeding and a small risk of death.3,4 Moreover, because fibrosis is not uniformly distributed in the liver and a biopsy only samples 1/50,000th to 1/30,000th of the liver mass,4,5 cirrhosis is missed in an estimated 15% to 30% of liver biopsies.5-7 The difficulties associated with liver biopsy have led to interest in the development of non-invasive testing to determine the degree of hepatic fibrosis.

Progressive degrees of fibrosis, and ultimately cirrhosis, are reflected in alterations in blood levels of various biomarkers (eg, as fibrosis increases, serum levels of α2-macroglobulin increase and those of apolipoprotein A1 decrease). The knowledge of such alterations has led to the development of predictive models based on clinically determined algorithms that utilize selected markers. One such model, the HepaScore, is based on serum levels of α2-macroglobulin, hyaluronic acid, gamma glutamyl transferase (GGT), and total bilirubin, along with age and sex. In one study, a HepaScore 0.5 (possible range, 0-1.0) was 63% sensitive and 89% specific for the presence of significant fibrosis (METAVIR F2), while a score <0.5 was 88% sensitive and 74% specific for excluding advanced fibrosis (METAVIR F3).8 In Quest Diagnostics’ internal validation using paired liver biopsy and serum samples from patients with HCV infection, the optimum cutoff was 0.55. Based on data from the entire population, a score of 0.55 was 83% sensitive and 65% specific for the presence of hepatic fibrosis METAVIR score F2.9 Using the same cutoff in a subset of subjects with more than 1 elevated analyte, the sensitivity and specificity increased to 88% and 69%, respectively.

Individuals Suitable for Testing

  • Individuals with chronic HCV infection


  • α2-Macroglobulin: fixed-time nephelometry

  • Bilirubin, Total: colorimetric

  • GGT: enzymatic/colorimetric

  • Hyaluronic acid: enzyme immunoassay

  • Report includes individual analyte concentrations, the HepaScore, patient-specific probability of having each METAVIR score (see Table for examples), the PPV and probability of a false-positive result when positive, and the NPV and probability of a false-negative result when negative (see Interpretive Information)

  • Synonym: Fibroscore

Interpretive Information

  • A HepaScore <0.55 is considered “negative” and indicates a METAVIR score of F0 or F1.

  • A HepaScore 0.55 is considered “positive” and indicates a METAVIR score of F2 to F4.

  • The patient-specific probability (P) of having a particular METAVIR score is based on the HepaScore sensitivity and specificity and the prevalence of liver fibrosis in either the entire population or the subset thereof (population described in the Clinical Background section).

  • The negative predictive value (NPV, probability that a negative test correctly indicates the absence of significant fibrosis) = P F0-F1.

  • The probability of a false-negative result =Σ(P F2 + P F3 + P F4).

  • The positive predictive value (ie, PPV, probability that a positive test correctly indicates significant fibrosis) = Σ(P F2 + P F3 + P F4).

  • The probability of a false-positive result = P F0-F1.

Example 1: Patient has a HepaScore of 0.9 (positive result) and more than 1 elevated analyte level; prevalence of significant fibrosis (METAVIR score 2) is 53%. The probability of having a specific METAVIR score is presented in the Table. The PPV is 83.8% and the probability of a false positive is 16.2%.

Example 2: Patient has a HepaScore of 0.2 (negative result) and no elevated analyte concentrations; prevalence of significant fibrosis is 50.1%. The probability of having a specific METAVIR score is presented in the Table. The negative predictive value is 86.4% and the probability of a false negative is 13.6%.

This test is meant as a screening tool to avoid unnecessary biopsies. The lowest and highest scores may obviate the need for a biopsy, while intermediary scores should be interpreted in the overall clinical context of the individual patient.

Table. Probability of Having a Specific METAVIR Score

METAVIR Score Example 1a   Example 2a
Probability  %   Probability %
F0-F1 16.2   86.4
F2 12.0   11.9
F3 22.2   1.7
F4 49.6   0.0

a See text for details of the example.


  1. Strader D, Wright T, Thomas D, et al. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004;39:1147-1171.

  2. Dienstag J. The role of liver biopsy in chronic hepatitis C. Hepatology. 2002;36:S152-160.

  3. McGill DB, Rakela J, Zinsmeister AR, et al. A 21-year experience with major hemorrhage after percutaneous liver biopsy. Gastroenterology. 1990;99:1396-1400.

  4. Cadranel JF, Rufat P, Degos F. Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Hepatology. 2000;32:477-481.

  5. Poynard T, Ratziu V, Bedossa P. Appropriateness of liver biopsy. Can J Gastroenterol. 2000;14:543-548.

  6. Regev A, Berho M, Jeffers LJ, et al. Sampling error and intraobserver variation in liver biopsy patients with chronic HCV infection. Am J Gastroenterol. 2002;97:2614-2618.

  7. Colloredo G, Guido M, Sonzogni A, et al. Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease. J Hepatol. 2003;39:239-244.

  8. Adams LA, Bulsara M, Rossi E, et al. Hepascore: an accurate validated predictor of liver fibrosis in chronic hepatitis C infection. Clin Chem. 2005;51:1876-1873.

  9. Data on file at Quest Diagnostics Nichols Institute, San Juan Capistrano, CA.

This test was developed and its performance characteristics have been determined by Quest Diagnostics Nichols Institute. It has not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. Performance characteristics refer to the analytical performance of the test.

Content reviewed 12/2012
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