FibroTest
Encyclopedia
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
, hepatitis B, alcoholic liver disease
, Non-alcoholic fatty liver disease
and in the general population. By 2008 it had been used in over 350,000 patients. 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.
, 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:
Due to variability of components assays and analyzers, FibroTest assays can only be performed in validated laboratories. 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 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.
, chronic hepatitis B, chronic hepatitis C or B with HIV co-infection, alcoholic liver diseases (steatosis and steatohepatitis), and non-alcoholic steatohepatitis (diabetes, overweight, hypertriglyceridemia, hypercholesterolemia, hypertension).
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, children, 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:
is:
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 and a 0.01-0.3% rate of deaths has been reported.
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. The inventors report that FibroTest has comparable diagnostic and prognostic value as a 25 mm biopsy, while being noninvasive and easily repeatable.
), 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.
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
tests to generate a score that is correlated with the degree of liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
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
Liver biopsy
Liver biopsy is the biopsy from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment.-History:...
(the current reference standard in liver disease assessment) in a large number of patients with hepatitis C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
, hepatitis B, alcoholic liver disease
Alcoholic liver disease
Alcoholic liver disease is a term that encompasses the hepatic manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with hepatic fibrosis or cirrhosis. It is the major cause of liver disease in Western countries...
, Non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease is one cause of a fatty liver, occurring when fat is deposited in the liver not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome and may respond to treatments originally developed for other insulin-resistant states...
and in the general population. By 2008 it had been used in over 350,000 patients. 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.
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, HaptoglobinHaptoglobin
Haptoglobin is a protein that in humans is encoded by the HP gene. In blood plasma, haptoglobin binds free hemoglobin released from erythrocytes with high affinity and thereby inhibits its oxidative activity. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system...
, Apolipoprotein A1
Apolipoprotein A1
Apolipoprotein A-I is a protein that in humans is encoded by the APOA1 gene. It has a specific role in lipid metabolism.Apolipoprotein A-I is the major protein component of high density lipoprotein in plasma. Chylomicrons secreted from the intestinal enterocyte also contain ApoA1 but it is quickly...
, Gamma-glutamyl transpeptidase (GGT), Total bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
, and Alanine transaminase
Alanine transaminase
Alanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
(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
Logistic regression
In statistics, logistic regression is used for prediction of the probability of occurrence of an event by fitting data to a logit function logistic curve. It is a generalized linear model used for binomial regression...
) is:
Due to variability of components assays and analyzers, FibroTest assays can only be performed in validated laboratories. 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 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 CHepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
, chronic hepatitis B, chronic hepatitis C or B with HIV co-infection, alcoholic liver diseases (steatosis and steatohepatitis), and non-alcoholic steatohepatitis (diabetes, overweight, hypertriglyceridemia, hypercholesterolemia, hypertension).
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, children, 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:
- 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 cardiac valves
- Gilbert's syndrome with high unconjugated hyperbilirubinemia
- Acute inflammatory syndrome (the blood test may be postponed)
Interpretation
The conversion of FibroTest score into stages according to the three most used histological classifications (METAVIR, Knodell and Ishak) for liver biopsiesLiver biopsy
Liver biopsy is the biopsy from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment.-History:...
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 biopsyLiver biopsy
Liver biopsy is the biopsy from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment.-History:...
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
Gold standard
The gold standard is a monetary system in which the standard economic unit of account is a fixed mass of gold. There are distinct kinds of 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 and a 0.01-0.3% rate of deaths has been reported.
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. The inventors report that FibroTest has comparable diagnostic and prognostic value as a 25 mm biopsy, while being noninvasive and easily repeatable.
FibroTest derivatives
Four other tests derive from FibroTest, and are part of the FibroMax package of tests:- ActiTest: diagnostic of necrotico-inflammatory for hepatitis;
- SteaoTest: diagnostic for liver steatosisSteatosisIn cellular pathology, steatosis is the process describing the abnormal retention of lipids within a cell. It reflects an impairment of the normal processes of synthesis and elimination of triglyceride fat. Excess lipid accumulates in vesicles that displace the cytoplasm...
;
- NashTest: diagnostic for NASHNash-Places:*Nash, Buckinghamshire, England*Nash, Herefordshire, England*Nash, Bromley, London Borough*Nash, Newport, Wales*Nash, Telford and Wrekin, former village in Shropshire, England*Nash, South Shropshire, England*Nash Lee, Buckinghamshire, England...
(Non-alcoholic fatty liver disease) inflammation;
- AshTest: diagnostic for Alcoholic liver diseaseAlcoholic liver diseaseAlcoholic liver disease is a term that encompasses the hepatic manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with hepatic fibrosis or cirrhosis. It is the major cause of liver disease in Western countries...
inflammation.
Patent, License
FibroTest tests and derivatives are patented since 2001 by APHP (Assistance publique - Hôpitaux de ParisAssistance publique - Hôpitaux de Paris
The Assistance publique – Hôpitaux de Paris is the public hospital system of the city of Paris and its suburbs...
), the Parisian public hospital system. In the US, FibroTest is marketed as FibroSure (a LabCorp
LabCorp
Laboratory Corporation of America Holdings , more commonly known as LabCorp, is an S&P 500 company headquartered in Burlington, North Carolina. It operates one of the largest clinical laboratory networks in the world, with a United States network of 36 primary laboratories. Before a merger with...
trademark). BioPredictive is the company licensed by APHP to promote and operate the tests.