Liver Fibrosis, FibroTest/ActiTest (Sendout)

Useful For:

• Evaluating hepatic fibrosis in chronic hepatitis C patients
• Diagnosing fibrosis in carriers of chronic hepatitis B virus
• Evaluating hepatic fibrosis in co-infected HIV carriers
• Providing access to new-generation non-interferon treatment for hepatitis
• Evaluating fibrosis in patients suffering from metabolic conditions (nonalcoholic fatty liver disease) and patients who consume excess alcohol

Testing Algorithm: This test is a patented test algorithm developed by BioPredictive. FibroTest combines 5 standard biomarkers (gamma-glutamyltransferase, total bilirubin, alpha-2-macroglobulin, apolipoprotein A1, and haptoglobin). The ActiTest adds a marker for inflammatory activity (alanine aminotransferase: ALT). These markers are weighted depending on the patient's age and gender.

Algorithm and interpretation provided through BioPredictive.

• Apolipoprotein A1: Automated Turbidimetric Immunoassay
• Alpha-2-Macroglobulin: Nephelometry
• Haptoglobin: Nephelometry
• Alanine Aminotransferase (ALT): Photometric Rate, L-Alanine with Pyridoxal-5-Phosphate
• Gamma Glutamyltransferase (GGT): Photometric Rate
• Bilirubin, Total: Photometric, Diazonium Salt (DPD)

Cautions:

Defer the test in transient situations that could modify the components of FibroTest-ActiTest, such as:

• Acute hemolysis, which could decrease haptoglobin and increase unconjugated bilirubin
• Acute hepatitis, whether drug-induced, viral (superinfection by hepatitis A virus: HAV, hepatitis B virus: HBV, Epstein-Barr virus: EBV), or autoimmune. Massive hepatic necrosis leads to a large increase of transaminases and total bilirubin.
• Acute inflammation, as with concomitant bacterial or acute viral infection: bronchopulmonary or urinary tract infection. The large increase of haptoglobin can lead to false-negative results.
• Extrahepatic cholestasis, such as gallstones

The advice of a liver disease specialist should be sought for interpretation in chronic states in which the components of the test could be modified, such as chronic hemolysis, particularly in patients with a cardiac valvular prosthesis; Gilbert disease; protease inhibitors used in HIV treatment, which can increase unconjugated bilirubin (Indinavir, Atazanavir); or gamma glutamyltransferase (GGT) and alanine aminotransferase (Ritonavir).

The interpretation of FibroTest has been validated in renal transplant patients. In patients with renal insufficiency or who are on dialysis, FibroTest had an acceptable diagnostic value, though lower than in transplanted patients.

As a general rule, isolated extreme values of 1 of the 6 components should signal caution in interpreting the results, particularly in the following cases:

• Haptoglobin below 12 mg/dL, in which hemolysis or anhaptoglobinemia (more frequent in western African patients) must be ruled out.
• Haptoglobin above 320 mg/dL, in which acute inflammation must be ruled out.
• Transaminases above 622 IU/L, in which acute hepatitis must be ruled out.
• Bilirubin above 1.75 mg/dL and GGT below 50 IU/L, in which Gilbert syndrome must be suspected.
• Alpha2-macroglobulin above 590 mg/dL

In case of discordance between a biopsy result and a FibroTest result, it is advisable to seek the advice of a liver disease specialist.

Haptoglobin is an acute-phase reactant and increases with inflammation or tissue necrosis. Low haptoglobin is normal for the first 3 to 6 months of life; testing is not performed on patients younger than 2 years-old per BioPredictive.

GGT activity is inducible by drugs such as phenytoin and phenobarbital and, therefore, elevations should not be considered indicative of liver disease until drug use is ruled out. Elevations are also seen after ingestion of alcoholic beverages. In very rare cases, gammopathy, in particular, type IgM (Waldenstrom macroglobinemia) may cause unreliable results.

Bilirubin specimens should be protected from light and analyzed as soon as possible. Grossly hemolyzed specimens should be rejected because hemoglobin inhibits the diazo reaction and falsely decreased results may be seen. Compounds that compete for binding sites on serum albumin contribute to lower serum bilirubin levels (eg, penicillin, sulfisoxazole, acetylsalicylic acid).

Outside Laboratories: Centrifuge sample and transfer 3 mL serum to a separate light-protected aliquot within two hours of collection. Alternatively, serum may be wrapped in foil to protect from light. Refrigerate serum.

• Centrifuged samples must be protected from light within 4 hours of collection.

Stability: Refrigerated (preferred): 7 days; Frozen: 14 days; Ambient: 24 hours.

Reject Due To:

• Gross hemolysis
• Gross lipemia
• Gross icterus
• Patients <2 years of age
• Sample not protected from light within 4 hours of collection

Centrifuge sample and transfer 1.5 mL serum to a separate light-protected/amber vial (Mayo supply T192) within two hours of collection. Refrigerate serum.

• Centrifuged samples must be protected from light within 4 hours of collection. It is acceptable to draw the blood and then protect it from light after centrifugation as long as it is within 4 hours of collection.

Sendouts: Order Mayo Test: FIBRO.

Stability: Refrigerated (preferred): 7 days; Frozen: 14 days; Ambient: 24 hours.

Reject Due To:

• Gross hemolysis
• Gross lipemia
• Gross icterus
• Patients <2 years of age
• Sample not protected from light within 4 hours of collection