FibroTest

FibroTest, known as FibroSure in the US, is a patented biomarker test that uses the results of six blood serum tests to generate a score that is correlated with the degree of liver damage in people with a variety of liver diseases. FibroTest has the same prognostic value as a liver biopsy.

FibroTest has been evaluated in relation to liver biopsy (the current reference standard in liver disease assessment) in a large number of patients with hepatitis C,[1] hepatitis B,[2] alcoholic liver disease,[3] Non-alcoholic fatty liver disease[4] and in the general population. By 2008 it had been used in over 350,000 patients.[2] FibroTest has been validated for the initial diagnosis of fibrosis, but also for the monitoring of patients. In 2006, the French National Authority for Health recommended the use of FibroTest as a first-line assessment tool for fibrosis with untreated chronic hepatitis C.[5]

Procedure

The FibroTest score is calculated from the results of a six-parameter blood test, combining six serum markers with the age and gender of the patient: Alpha-2-macroglobulin, Haptoglobin, Apolipoprotein A1, Gamma-glutamyl transpeptidase (GGT), Total bilirubin, and Alanine transaminase (ALT). ALT is used in a second assessment called ActiTest that is part of FibroTest.

The equation for calculating the FibroTest score regression coefficient (logistic regression) is:[6]

z=4.467\times \log_{10} [\alpha2 macroglobulin (g/L)]-1.357\times\log_{10} [Haptoglobin (g/L)] + 1.017 \times \log_{10} [GGT (IU/L)] + 0.0281 \times [Age (years)]

+ 1.737 \times \log_{10} [Bilirubin (\mu mol/L)] - 1.184 \times [Apo A1 (g/L)] + 0.301 \times Sex (female=0, male=1)-5.54

Due to variability of components assays and analyzers, FibroTest assays can only be performed in validated laboratories.[7] FibroTest cannot be used without algorithms that detects false positives and false negatives; the equation alone is not a diagnosis tool.

The laboratory or physician connects to the BioPredictive website[8] for calculation of the test results and prints the results sheet, which is available immediately and is accompanied by an interpretation aid and precautions for use.

Applicability

Over 95% of tests are interpretable and allow a diagnosis of fibrosis and liver activity. In less than 5% of cases, likely false positives or false negatives are highlighted. FibroTest has been validated for chronic hepatitis C,[1] chronic hepatitis B,[2] chronic hepatitis C or B with HIV co-infection,[9] alcoholic liver diseases (steatosis and steatohepatitis),[3] and non-alcoholic steatohepatitis (diabetes, overweight, hypertriglyceridemia, hypercholesterolemia, hypertension).[4]

FibroTest is independent of ethnic origin, sex, genotype, viral load, transaminases or the presence of comorbidities. The test has been validated in those over the age of 65 years,[10] children,[11] patients with renal insufficiency or renal transplanation, hemophiliacs, patients with chronic inflammatory disease, and the general population.

The tests are not applicable in 1 to 5% of cases. These cases can be detected by laboratory safety algorithms and when detected they are indicated on the results sheet:[2]

Interpretation

FibroTest result
The FibroTest score (in this case 0.88) may indicate the presence of cirrhosis.

The conversion of FibroTest score into stages according to the three most used histological classifications (METAVIR, Knodell and Ishak) for liver biopsies is:

FibroTest METAVIR Knodell Ishak
0.75-1.00 F4 F4 F6
0.73-0.74 F3-F4 F3-F4 F5
0.59-0.72 F3 F3 F4
0.49-0.58 F2 F1-F3 F3
0.32-0.48 F1-F2 F1-F3 F2-F3
0.28-0.31 F1 F1 F2
0.22-0.27 F0-F1 F0-F1 F1
0.00-0.21 F0 F0 F0

Comparison with liver biopsy

Liver biopsy is an imperfect tool; due to sampling errors, biopsy size (5 to 30 mm) and intra- and interobservor variability, it is now agreed that biopsy is an "imperfect Gold Standard". Biopsy continues to present inconveniences: 30% of patients complain of pain, up to 3% have been noted to have complications severe enough to require hospitalization[12][13] and a 0.01-0.3% rate of deaths has been reported.[14][15][16]

There is a mean discordance of 25% between FibroTest and biopsy. Half of these discordances are attributable to an error of the biopsy, often too small, and the other half to FibroTest.[17] The inventors report that FibroTest has comparable diagnostic and prognostic value as a 25 mm biopsy, while being noninvasive and easily repeatable.[1][3][18]

FibroTest derivatives

Four other tests derive from FibroTest, and are part of the FibroMax package of tests:

Patent, License

FibroTest tests and derivatives are patented since 2001 by APHP (Assistance publique - Hôpitaux de Paris), the Parisian public hospital system. In the US, FibroTest is marketed as FibroSure (a LabCorp trademark). BioPredictive is the company licensed by APHP to promote and operate the tests.

References

  1. ↑ 1.0 1.1 1.2 Ngo Y, Munteanu M, Messous D, Charlotte F, Imbert-Bismut F, Thabut D, Lebray P, Thibault V,Benhamou Y, Moussalli J, Ratziu V, Poynard T (2006). "A prospective analysis of the prognostic value of biomarkers (FibroTest) in patients with chronic hepatitis C". Clin Chem 52 (10): 1887–96. doi:10.1373/clinchem.2006.070961. PMID 16931569.
  2. ↑ 2.0 2.1 2.2 2.3 Halfon P, Munteanu M, Poynard T (2008). "FibroTest-ActiTest as a non-invasive marker of liver fibrosis". Gastroenterol Clin Biol 32 (6): 22–39. doi:10.1016/S0399-8320(08)73991-5. PMID 18973844.
  3. ↑ 3.0 3.1 3.2 Naveau et al. (2009). "Diagnostic and prognostic values of non-invasive biomarkers of fibrosis in patients with alcoholic liver disease". Clin Gastroenterol Hepatol 49 (2): 97–10. doi:10.1002/hep.22576. PMID 15704051.
  4. ↑ 4.0 4.1 Ratziu et al. (2006). "Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease". BMC Gastroenterology 6: 6. doi:10.1186/1471-230X-6-6. PMC 1386692. PMID 16503961.
  5. ↑ Publication of 'Haute Autorité de Santé' (fr)
  6. ↑ U.S. patent 6,631,330
  7. ↑ Imbert-Bismut F; Messous D; Thibault V; Myers RB; Piton A; Thabut D et al. (2004). "Intra-laboratory analytical variability of biochemical markers of fibrosis (Fibrotest) and activity (Actitest) and references ranges in healthy blood donors". Clin Chem Lab Med 42 (3): 323–333. doi:10.1515/CCLM.2004.058. PMID 15080567.
  8. ↑ FibroTest website
  9. ↑ Cacoub P, Carrat F, Bédossa P, Lambert J, Pénaranda G, Perronne C, Pol S, Halfon P. (2008). "Comparison of non-invasive liver fibrosis biomarkers in HIV/HCV co-infected patients: The Fibrovic study - ANRS HC02". J Hepatol. 48 (5): 765–73. doi:10.1016/j.jhep.2008.01.025. PMID 18314219.
  10. ↑ Thabut et al. (2006). "Hepatitis C in 6,865 patients 65 yr or older: a severe and neglected curable disease". Am J Gastroenterol. 101 (6): 1260–7. doi:10.1111/j.1572-0241.2006.00556.x. PMID 16771947.
  11. ↑ Hermeziu B et al. (2009). "Evaluation of FibroTest-ActiTest in children with chronic hepatitis C virus infection". Gastroenterol Clin Biol 34 (1): 16–22. doi:10.1016/j.gcb.2009.06.007. PMID 19726147.
  12. ↑ Janes and Lindor; Lindor, KD (1993). "Outcome of patients hospitalized for complications after outpatient liver biopsy". Ann Intern Med 118 (2): 96–8. doi:10.7326/0003-4819-118-2-199301150-00003. PMID 8416324.
  13. ↑ Pasha T, Gabriel S, Therneau T, Dickson ER, Lindor KD (1998). "Cost-effectiveness of ultrasound-guided liver biopsy". Hepatology 27 (5): 1220–6. doi:10.1002/hep.510270506. PMID 9581674.
  14. ↑ Strassburg CP, Manns MP (2006). "Approaches to liver biopsy techniques-revisited". Semin Liver Dis 26 (4): 318–27. doi:10.1055/s-2006-951599. PMID 17051446.
  15. ↑ Gilmore IT, Burroughs A, Murray-Lyon IM, Williams R, Jenkins D, Hopkins A (1995). "Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London". Gut 36 (3): 437–41. doi:10.1136/gut.36.3.437. PMC 1382461. PMID 7698705.
  16. ↑ Froehlich F, Lamy O, Fried M, Gonvers JJ (1993). "Practice and complications of liver biopsy. Results of a nationwide survey in Switzerland". Dig Dis Sci 38 (8): 1480–4. doi:10.1007/bf01308607. PMID 8344104.
  17. ↑ Poynard et al. (2004). "Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C". Clin Chem 50 (8): 1344–55. doi:10.1373/clinchem.2004.032227. PMID 15192028.
  18. ↑ Ngo et al. (2008). Ahmed, Niyaz, ed. "An accurate definition of the status of inactive hepatitis B virus carrier by a combination of biomarkers (FibroTest-ActiTest) and viral load". PLoS ONE 3 (7): e2573. doi:10.1371/journal.pone.0002573. PMC 2440801. PMID 18596917.

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