Sequential non-invasive tests more accurate for NAFLD than single or simultaneous

Performing sequential non-invasive tests more accurately measured severity of fatty liver than single tests or simultaneous tests, according to a researcher at The Liver Meeting Digital Experience.

“Sequential strategies may decrease the need for liver biopsy while maintaining accuracy of non-invasive diagnosis in patients with advanced fibrosis due to NASH,” Jerome Boursier, MD, PhD, of Angers University Hospital and Laboratoire Hifih, said during his presentation. “At the risk of a decrease in sensitivity, the sequential approach maintains accuracy while reducing misclassification, which makes this method the best option for medical practice.”

Boursier and colleagues analyzed all participants in the REGENERATE study (n = 4,133) using five different non-invasive tests (NITs): aspartate transaminase-to-platelet ratio index (APRI), enhanced liver fibrosis (ELF), fibrosis-4 (FIB-4), NAFLD fibrosis score (NFS) and transient elastography (TE). They set the upper and lower cutoffs for each and between those cutoffs was considered indeterminate. They then used the tests individually, simultaneously with equal weighting and sequentially where the second NIT performed only when the first was indeterminate.

When used individually, Boursier reported TE had the lowest rate of indeterminate classification at 16.9%. Single NITs with upper thresholds demonstrating strong specificity for identification of advanced fibrosis were FIB-4 (97%), NFS (94%), and APRI (86%); NITs with lower thresholds demonstrating good sensitivity for identification of early fibrosis were ELF (100%) and TE (88%).

“No single test was optimal for both sensitivity and specificity and single tests also had a large indeterminate zone, which is undesirable in clinical practice,” Boursier said.

Simultaneous NIT evaluation resulted in a greater percentage of patients who fell into the indeterminate area from 65.8% with FIB-4 and TE to 92.5% with NFS and ELF, though all combinations were high in sensitivity and specificity.

“Simultaneous use of NITs increased the accuracy of the results but dramatically expanded the indeterminate zone,” Boursier said.

Sequential NIT evaluation, though, resulted in much smaller percentages of patients in the indeterminate zone from 3.5% with FIB-4 and then TE to 12.9% using NFS and then ELF.

“Such approach dramatically reduced the rate of patients with indeterminate diagnosis to lower than 15%,” Boursier said.

Boursier showed that age impacted the indeterminate zone when using FIB-4 alone with nearly 60% of patients older than 65 years falling in the gray area. Simultaneous use of FIB-4 and TE had similarly large percentages of patients in the indeterminate area but using the same NITs sequentially reduced the indeterminate percentage to 6.8% of those older than 65.

“Interestingly, adding TE to FIB-4 erased the effect of age,” he said.

“The population evaluated in this analysis includes a large sample size of patients from more than 250 global study sites and may be representative of patients seen in routine real-world clinical practice,” Boursier said. “Sequential combinations of multiple non-invasive tests warrant further evaluation in clinical trial and real-world settings.”