Utility and limitations of Hepascore and transient elastography to detect advanced hepatic fibrosis in HFE hemochromatosis

Sim Yee Ong,John K Olynyk,Lyle Gurrin,Adam Testro,Richard Skoien,Louise E Ramm,Tiffany Khoo,Martin B Delatycki,Gregory J Anderson,Puraskar Pateria,Lawrie W Powell,Grant A Ramm,Amanda J Nicoll,Thomas Worland

doi:10.1038/s41598-021-94083-x

Abstract

Aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 Index (Fib4) have been validated against liver biopsy for detecting advanced hepatic fibrosis in HFE hemochromatosis. We determined the diagnostic utility for advanced hepatic fibrosis of Hepascore and transient elastography compared with APRI and Fib4 in 134 newly diagnosed HFE hemochromatosis subjects with serum ferritin levels > 300 µg/L using area under the receiver operator characteristic curve (AUROC) analysis and APRI- (> 0.44) or Fib4- (> 1.1) cut-offs for AHF, or a combination of both. Compared with APRI, Hepascore demonstrated an AUROC for advanced fibrosis of 0.69 (95% CI 0.56–0.83; sensitivity = 69%, specificity = 65%; P = 0.01) at a cut-off of 0.22. Using a combination of APRI and Fib4, the AUROC for Hepascore for advanced fibrosis was 0.70 (95% CI 0.54–0.86, P = 0.02). Hepascore was not diagnostic for detection of advanced fibrosis using the Fib4 cut-off. Elastography was not diagnostic using either APRI or Fib4 cut-offs. Hepascore and elastography detected significantly fewer true positive or true negative cases of advanced fibrosis compared with APRI and Fib4, except in subjects with serum ferritin levels > 1000 µg/L. In comparison with APRI or Fib4, Hepascore or elastography may underdiagnose advanced fibrosis in HFE Hemochromatosis, except in individuals with serum ferritin levels > 1000 µg/L.

Highlights

Some noninvasive fibrosis biomarkers have been validated against liver biopsy for detection of AHF in HH
We evaluated two noninvasive biomarker models for the detection of AHF in HH: Model 1 used individual values for APRI > 0.44 or Fib4 > 1.1 to define the presence of probable noninvasive biomarker-detected AHF
Liver biochemistry was within accepted reference ranges, as were the platelet count and international normalised ratio (INR) (Table 1)

Summary

Introduction

Some noninvasive fibrosis biomarkers have been validated against liver biopsy for detection of AHF in HH. The aspartate aminotransferase (AST)-to-platelet ratio index (APRI, cut-off value > 0.44) and Fibrosis-4 Index (Fib[4], cut-off value > 1.1) demonstrate good diagnostic utility for the detection of AHF in HH with area under the receiver operator characteristic curve (AUROC) of 0.88 and 0.86, correctly identifying liver biopsy-diagnosed AHF in 85% and 80% of cases, respectively[17] Another commonly used biomarker, Hepascore, is available for detection of AHF in chronic liver diseases, but has not been validated in HH. Transient elastography (TE) is an increasingly common non-invasive method fer detecting AHF in a range of liver diseases, but has not been validated in HH20–27 It relies on mechanical or acoustic modalities generating shear waves which are measured by ultrasound and converted to a stiffness estimate. Since APRI and Fib[4] have been recently validated as noninvasive biomarkers of advanced hepatic fibrosis in H H17, the aims of our study were to (1) determine the diagnostic utility of Hepascore and TE in comparison with APRI- and Fib4determined cut-offs for the detection of probable AHF, and (2) evaluate their responses to phlebotomy treatment

Objectives

Methods

Conclusion