Fibrosis-4 index followed by measurement of liver stiffness with vibration-controlled transient elastography or Enhanced Liver Fibrosis test maintained acceptable noninvasive performance in identifying advanced fibrosis due to nonalcoholic steatohepatitis while reducing the rate of indeterminate results, according to an analysis of the STELLAR trial outcomes.
“Even the most effective treatment will not be able to address this large unmet medical need without a practical method to identify patients most in need of treatment,” Quentin M. Anstee, PhD, from Newcastle University in the United Kingdom, and colleagues wrote. “Such a method would have the additional benefit of reducing unnecessary drug exposure and costs in patients least likely to benefit from therapy.”
The analysis included data from 3,202 patients, most of whom had stage 3 (31%) or stage 4 fibrosis (40%). The AUROCs to discriminate advanced fibrosis were 0.74 for NAFLD fibrosis score (NFS), 0.78 for Fibrosis4 index (FIB-4), and 0.8 for Enhanced Liver Fibrosis test (ELF) and liver stiffness by vibrationcontrolled transient elastography (LS by VCTE).
Simultaneous use of two noninvasive tests improved sensitivity (89% or higher) and specificity (97% or higher) compared with a single noninvasive test, but “predictably” increased the proportion of patients who fell in the indeterminate zone.
“Due to this high rate of indeterminate results with the simultaneous combination approach, we explored the use of two [noninvasive tests] in sequential combination for discriminating advanced fibrosis,” the researchers wrote.
Patients were classified using one test with lower and upper thresholds, then a second test with two thresholds to categorize those who fell in the indeterminate zone. This approach reduced the frequency of indeterminate results to as low as 20% with generally acceptable sensitivity and specificity.
Adding a third test, such as FIB-4 followed by ELF and then LS by VCTE, further reduced the indeterminate zone to 10% or less, although the misclassification rate increased using literature-based and novel thresholds.
“We have shown that commonly available [noninvasive tests] perform well in identifying patients with advanced fibrosis due to NASH,” Anstee and colleagues wrote. “While there is some expected inaccuracy, particularly when compared to an imperfect reference standard like liver biopsy, the degree of diagnostic inaccuracy that will be acceptable will ultimately depend on the efficacy and safety of new treatments.” – by Talitha Bennett
Disclosure: The researchers report that Gilead Sciences provided the primary funding for this analysis.