FibroTest
FibroTest, known as FibroSure in the US, is a 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. FibroSure uses quantitative results of five serum biochemical markers, α2-macroglobulin, haptoglobin, apolipoprotein A1, bilirubin, gamma glutamyl transpeptidase (GGT), with a patient’s age and gender to generate a measure of fibrosis and necroinflammatory activity in the liver.
FibroTest | |
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Purpose | assess degree of liver damage |
FibroTest has been evaluated in relation to liver biopsy (the current reference standard in liver disease assessment) in people with hepatitis C, hepatitis B,[1] alcoholic liver disease,[2] and non-alcoholic fatty liver disease.[3] They are most useful for cirrhosis and less useful for other stages of liver disease.[4]
By 2008 it had been used in over 350,000 patients.[5] In 2006, the French National Authority for Health recommended the use of FibroTest as one of a number of first-line assessment tool for fibrosis with untreated chronic hepatitis C.[6]
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:[7]
where B=1 for male and B=0 for female. The score (between 0 and 1) is then
Due to variability of components assays and analyzers, FibroTest assays can only be performed in validated laboratories.[8] 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[9] 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,[10] chronic hepatitis B,[5] chronic hepatitis C or B with HIV co-infection,[11] alcoholic liver diseases (steatosis and steatohepatitis),[2] and non-alcoholic steatohepatitis (diabetes, overweight, hypertriglyceridemia, hypercholesterolemia, hypertension).[3]
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,[12] children,[13] people with chronic kidney disease or kidney transplantation, 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:[5]
- Acute hepatitides, e.g., acute viral hepatitis A, B, C, D, E; drug-induced hepatitis
- Extrahepatic cholestasis, e.g., pancreatic cancer, gallstones
- Severe hemolysis, e.g., some heart valves
- Gilbert's syndrome with high unconjugated hyperbilirubinemia
- Acute inflammatory syndrome (the blood test may be postponed)
Interpretation
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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 " (citation required). 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[14][15] and a 0.01-0.3% rate of deaths has been reported.[16][17][18] 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.[19] The inventors report that FibroTest has comparable diagnostic and prognostic value as a 25 mm biopsy, while being noninvasive and easily repeatable.[10][2][20]
References
- Houot, M; Ngo, Y; Munteanu, M; Marque, S; Poynard, T (January 2016). "Systematic review with meta-analysis: direct comparisons of biomarkers for the diagnosis of fibrosis in chronic hepatitis C and B." Alimentary Pharmacology & Therapeutics. 43 (1): 16–29. doi:10.1111/apt.13446. PMC 4737301. PMID 26516104.
- Naveau S (2009). "Diagnostic and prognostic values of non-invasive biomarkers of fibrosis in patients with alcoholic liver disease". Clin Gastroenterol Hepatol. 49 (1): 97–105. doi:10.1002/hep.22576. PMID 19053048. S2CID 5782597.
- 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.
- Shaheen, AA; Wan, AF; Myers, RP (November 2007). "FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: a systematic review of diagnostic test accuracy". The American Journal of Gastroenterology. 102 (11): 2589–600. doi:10.1111/j.1572-0241.2007.01466.x. PMID 17850410. S2CID 8104445.
- 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.
- Publication of 'Haute Autorité de Santé' (fr)
- "U.S. patent 6,631,330". Archived from the original on 2012-10-11. Retrieved 2011-01-23.
- 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. S2CID 21074850.
- FibroTest website
- 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.
- 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.
- 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. S2CID 2451830.
- 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. S2CID 42805970.
- Janes, CH & 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. S2CID 37740050.
- 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.
- 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.
- 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.
- 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. S2CID 21781162.
- 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.
- 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. Bibcode:2008PLoSO...3.2573N. doi:10.1371/journal.pone.0002573. PMC 2440801. PMID 18596917.