Validation of Shear Wave Elastography Cutoff Values on the Supersonic Aixplorer for Practical Clinical Use in Liver Fibrosis Staging

Abstract

The purpose of this study was to determine the validity of previously established ultrasound shear wave elastography (SWE) cut-off values (≥F2 fibrosis) on an independent cohort of patients with chronic liver disease. In this cross-sectional study, approved by the institutional review board and compliant with the Health Insurance Portability and Accountability Act, 338 patients undergoing liver biopsy underwent SWE using an Aixplorer ultrasound machine (SuperSonic Imagine, Aix-en-Provence, France). Median SWE values were calculated from sets of 10 elastograms. A single blinded pathologist evaluated METAVIR fibrosis staging as the gold standard. The study analyzed 277 patients with a mean age of 48 y. On pathologic examination, 212 patients (76.5%) had F0–F1 fibrosis, whereas 65 (23.5%) had ≥F2 fibrosis. Spearman's correlation of fibrosis with SWE was 0.456 (p < 0.001). A cut-off value of 7.29 kPa yielded sensitivity of 95.4% and specificity of 50.5% for the diagnosis of METAVIR stage ≥F2 liver fibrosis in patients with liver disease using the SuperSonic Imagine Aixplorer SWE system.

Introduction

Hepatitis C viral disease (HCV), hepatitis B viral disease (HBV), nonalcoholic fatty liver disease (NAFLD), autoimmune hepatitis (AIH) and alcoholic liver disease (ALD) are forms of chronic liver disease (CLD) that share a common pathway of progressive liver fibrosis, which may ultimately culminate in cirrhosis (Sebastiani et al. 2011). Management of these various forms of CLD is centered on attempts to reverse early fibrosis and prevent progression to cirrhosis. Although non-focal liver biopsy is currently the reference standard for fibrosis staging in patients with known liver disease, it is invasive and expensive, and is limited by inter-observer variability and sampling error (Regev et al. 2002).

Various imaging techniques including morphologic analysis, CT-perfusion analysis (Ronot et al. 2010), MR-perfusion analysis (Hagiwara et al. 2008), water diffusion imaging (Bonekamp et al., 2011, Wang et al., 2012) and elastography have been shown to predict liver fibrosis stage with varying degrees of accuracy. As a non-invasive, inexpensive and portable technique, ultrasound (US) elastography has shown promising results (Chon et al., 2012, Friedrich-Rust et al., 2008, Friedrich-Rust et al., 2012). In particular, shear wave elastography (SWE) derived estimates of shear wave speed and hepatic Young's modulus, measured in kilopascal (kPa) have been shown to be related to liver fibrosis stage (Beland et al., 2014a, Deffieux et al., 2015, Feng et al., 2016, Jeong et al., 2014, Sporea et al., 2014a, Tada et al., 2015, Zheng et al., 2015). Cut-off eYM or shear wave speed values for different liver fibrosis stages have been proposed in a number of studies (Beland et al., 2014a, Jeong et al., 2014, Samir et al., 2015). A recent meta-analysis of SWE studies summarizes this dilemma wherein 12 manuscripts reviewed have generated 12 different cut-off values for variable sensitivities and specificities (Feng et al. 2016). To date, these cut-off values have not been prospectively validated in data sets independent of those used to generate the cut-off values, making it extremely difficult for clinicians to decide on which set of values to base a clinical decision. A recent editorial by experts in the field has also pointed out these challenges from a clinical standpoint (Piscaglia et al. 2016).

The purpose of this study was to evaluate the validity of our previously established eYM cut-off values for staging liver fibrosis (Samir et al. 2015) in an independent cohort of patients with diffuse liver disease.