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June 28, 2021
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Elastography, bloodwork combine for 'super test' to diagnose advanced liver fibrosis

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Using clinical bloodwork like FIB-4 and elastography technology in combination, researchers at the International Liver congress proposed they could better identify patients with advanced fibrosis using clinical bloodwork like FIB-4 and elastography technology in combination.

“The idea of this study was to combine both methods – elasticity measured by Fibroscan and the blood marker – in a single quite super test for the diagnosis of advanced liver fibrosis,” Jerome Boursier, MD, PhD, of Angers University Hospital in France, said during the press conference. “Agile 3+ that combines the Fibroscan with simple parameters – transaminases, platelets and clinical data ... – significantly improves the accuracy, the ability to detect advanced liver fibrosis compared with Fibroscan alone or to blood tests alone.”

In developing Agile 3+, Boursier and colleagues hoped to use common non-invasive tests in combination to limit the area of uncertainty in diagnosing or excluding the diagnosis of advanced fibrosis.

This retrospective study included seven cohorts of adults with suspected NAFLD who underwent biopsy, liver stiffness measurement with Fibroscan (Echosens) elastography and blood sampling in routine clinical practice or clinical trial.

Researchers randomly divided the cohorts into a training set (n = 1,434), on which they built the model, and an internal validation set (n = 700), on which they assessed the performance of the model. They conducted validation on both a U.S. cohort (n = 585) and a French cohort (n = 1,042). The implementation of 14 variables into a multivariate logistic regression model aimed to create cutoff values with high sensitivity to rule out NAFLD and high specificity to rule in NAFLD, eventually decreasing the number of indeterminate cases.

By using the data together, the combination elastography with platelets, sex, age and diabetes bloodwork outperformed elastography or FIB-4 alone. The area under the curve stepped up from 0.82 (95% CI, 0.8-0.84) for FIB-4 to 0.86 (95% CI, 0.84-0.88) for liver stiffness measurement to 0.9 (95% CI, 0.88-0.91) for Agile 3+, making it significantly more accurate (both P < .0001). With high rule-out cutoff and high rule-in cutoff, the number of indeterminate cases is just 13% with Agile 3+ vs. 30% with FIB-4 and 23% with liver stiffness measurement.

“Agile 3+, because it is more accurate for the diagnosis of advanced fibrosis, has significantly reduced the grey zone to less than 20%, which is much less than Fibroscan,” Boursier said. “It helps to organize the flux of patients between primary care and tertiary care. You have less patients without advanced liver fibrosis who are referred to the specialty ... and you increase the detection of patients with advanced liver fibrosis.”

Agile 3+ continued to outperform the other tests in the validation cohorts, with the indeterminate cases coming in at 17% and 18%.

“This innovative combination of blood markers with Fibroscan into a single super test improves the diagnostic accuracy and reduces the requirement for biopsy because the grey zone is much smaller, which is very interesting for clinical practice and identification of those patient in need for specialized management among the large population of NAFLD patients,” Boursier said.