A: FibroTest-ActiTest and NASH-FibroTest are proprietary algorithms developed and patented by BioPredictive. These algorithms utilize the patient’s age and sex, along with measurement of serum biomarkers, to estimate liver fibrosis/cirrhosis, necroinflammatory activity, steatosis, and nonalcoholic steatohepatitis (NASH).

FibroTest-ActiTest measures gamma-glutamyltransferase (GGT) activity, total bilirubin, alpha-2-macroglobulin, apolipoprotein A1, haptoglobin, and alanine aminotransferase (ALT) activity in the patient’s serum. The BioPredictive algorithm then calculates a fibrosis score between 0−1 that corresponds to a fibrosis stage (F0−F4) and an activity score between 0−1 that translates to an activity or inflammatory stage (A0−A4). On the FibroTest relative scale, F0=no fibrosis and F4=severe fibrosis (cirrhosis). FibroTest is useful for diagnosing fibrosis in carriers of chronic hepatitis B, patients with chronic hepatitis C, and patients with metabolic conditions such as nonalcoholic fatty liver disease (NAFLD) or alcoholic liver disease.

NASH-FibroTest includes the components of FibroTest-ActiTest and the following additional serum/plasma tests: aspartate aminotransferase (AST) activity, cholesterol, triglycerides, and fasting glucose. In addition to FibroTest for estimating liver fibrosis, NASH-FibroTest includes SteatoTest2 to assess hepatic steatosis and NashTest2 to evaluate the level of necroinflammatory activity caused by NASH. Steatosis is reported relative to a scale ranging from S0-S2S3 (S0=no steatosis (<5%), S1=mild steatosis (5−33%), S2/S3=moderate/severe steatosis (34−100%)). A stage of S1 or S2S3 is considered clinically significant. NashTest 2 is reported relative to a scale ranging from N0−N3 (N0=no NASH, N3=severe NASH).

How does FibroTest compare to other noninvasive tests and liver biopsy for diagnosing liver fibrosis?

There are several noninvasive methods for assessing liver fibrosis, and each has its strengths and weaknesses. Numerous serum biomarker panels exist. Tests such as the AST-to-platelet ratio index (APRI) and FIB4 score (calculated from age, AST, ALT, and platelet count) are widely available as they utilize common lab tests and can be easily calculated by the healthcare provider using a calculator or app. A few other proprietary testing algorithms exist as well. 

Imaging techniques include ultrasound-based transient elastography (TE) and magnetic resonance elastography (MRE) among others. TE assesses the “stiffness” of the liver and has been widely evaluated, but it requires high-cost equipment, proper calibration, and trained operators. MRE has sufficient accuracy for staging liver fibrosis, but it’s costly, requires the use of two contrast agents, and its availability is limited to select advanced tertiary care centers. 

There are more than 300 peer-reviewed publications evaluating FibroTest in various patient populations. Houot and colleagues published a systematic review with meta-analysis that directly compared common biomarker panels (APRI and FIB4), FibroTest, and TE with biopsy for the diagnosis of fibrosis in chronic hepatitis C and B patients (Ailment Pharmacol Ther 2016;43:1629). FibroTest performed slightly better than TE and APRI for identifying advanced fibrosis (F2F4) and was comparable to TE and FIB4 for identifying cirrhosis. The general consensus in the literature is that noninvasive methods, including FibroTest, are very good for detecting severe liver fibrosis and cirrhosis and for ruling out fibrosis.

How do reference labs offer this testing?

BioPredictive holds an international patent for FibroTest-ActiTest and NASH-FibroTest.  However, because the serum analytes used in the company’s proprietary algorithms are readily available Food and Drug Administration-cleared lab tests, labs can enter into a licensing agreement with BioPredictive and offer the testing to their laboratory clients. The clinical laboratory must adhere to BioPredictive’s technical recommendations for the assays, which include specifications for methodology, specimen requirements, calibration, and assay imprecision. Test results and patient age and sex are securely transmitted to BioPredictive, the algorithm is applied, and scores and stages are returned to the performing laboratory.

Nikola A. Baumann, PhD, is co-director of the Central Clinical Laboratory and Central Processing at the Mayo Clinic in Rochester, Minnesota. +Email: [email protected]