New blood test helps spot hidden liver scarring earlier
'Simple, affordable, practical' test can be used in primary care
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A new add-on blood test called the FAP-Index may help accurately identify serious liver scarring in people with metabolic dysfunction-associated steatotic liver disease (MASLD), a study found.
“Fatty liver disease is incredibly common but it’s very difficult to know who has severe liver damage,” Ziqi Vincent Wang, the study’s first author and a graduate student at the Centenary Institute and the University of Sydney, in Australia, said in an institute press release. “The FAP-Index is designed to be simple, affordable and practical, so it can be used early in primary care to identify patients who genuinely need further investigation.”
The study, “A Novel Fibroblast Activation Protein-Based Algorithm to Assess Fibrosis in Metabolic Dysfunction–Associated Steatotic Liver Disease,” was published in the Journal of Gastroenterology and Hepatology.
MASLD is a disorder marked by the abnormal buildup of liver fat in people who typically have underlying metabolic conditions such as diabetes or high blood pressure. The buildup of liver fat can lead to inflammation and fibrosis (scarring) that damages the liver and sets the stage for life-threatening complications.
Testing may be costly, invasive
Liver biopsy, in which a small piece of tissue is collected and analyzed under a microscope, is the most accurate way to measure liver fibrosis. However, it’s an invasive, costly procedure that can increase the risk of certain complications, such as bleeding or pain. Elastography, an advanced imaging test, can also assess liver fibrosis, but it isn’t always accessible. In real-world practice, doctors often rely on easily accessible, noninvasive blood tests to assess liver fibrosis.
“In MASLD, the two most commonly used [tests] are NAFLD fibrosis score (NFS) and Fibrosis Index 4 (FIB-4),” the researchers wrote.
NAFLD, short for non-alcoholic fatty liver disease, is an outdated term for MASLD. Both tests combine demographic and laboratory data. However, they often yield indeterminate results, placing the person at intermediate risk and making it impossible to determine whether they have substantial scarring.
Wang and colleagues developed the new add-on test to minimize indeterminate results, enabling accurate fibrosis testing without requiring additional invasive tests.
The FAP-Index incorporates blood levels of fibroblast activation protein alpha (FAP), which helps activate fibroblasts, the main cells responsible for making scar tissue. The test also takes into account a person’s age, diabetes status, and blood levels of a liver damage marker called alanine transaminase.
The new index “can be a readily applied primary care test because it contains variables that are easily obtained,” the researchers wrote, noting that FAP protein levels can be measured with the same basic technology used to measure standard liver damage markers.
To evaluate the accuracy of the FAP-Index, the researchers used data from two groups of MASLD patients. The training group was comprised of 160 patients, 20% of whom had advanced fibrosis, as confirmed by biopsy analysis. The validation group had 332 patients, including 11% with advanced fibrosis.
The researchers calculated a statistical metric called the area under the receiver operating characteristic curve (AUROC), which measures how well a test discriminates between two groups — in this case, patients with or without advanced fibrosis. AUROC values range from 0 to 1, with 0.5 indicating random guessing and higher values indicating greater accuracy.
Results showed an AUROC of 0.875 in the training group and 0.841 in the validation group, indicating high accuracy on par with the established FIB-4 and NFS.
The researchers then tested whether applying the FAP-Index after standard tests could reduce indeterminate results. Each combination “reduced the indeterminate percentage while [not] compromising … diagnostic accuracy,” the team wrote.
FIB-4 followed by FAP index was associated with a 30%-40% reduction in indeterminate results relative to FIB-4 alone. NFS followed by FAP index was linked to a reduction of about 70% in indeterminate results compared with NFS alone.
“FAP Index is a novel, [fibrosis-relevant], rapid, robust diagnostic tool suited to increasing the efficiency of liver fibrosis triage in primary care,” the researchers wrote.
“With effective therapies becoming available, there is an urgent need for better tools to test patients and more accurately detect advanced fibrosis earlier,” said Mark Gorrell, PhD, co-senior author of the study and laboratory head in the Centenary Institute’s Centre for Cancer Innovations. “By focusing on a protein central to liver scarring and reducing uncertain results, the FAP-Index has the potential to ease pressure on specialist services while ensuring patients in need receive timely care.”
