Research ArticleValidity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter
Graphical abstract
Introduction
Non-alcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide and has become an important cause of end-stage liver disease and hepatocellular carcinoma.[1], [2], [3], [4] The presence of fatty liver and metabolic syndrome in patients with chronic viral hepatitis is also associated with increased risk of cirrhosis and hepatocellular carcinoma.[5], [6], [7], [8] Abdominal ultrasonography is commonly used to diagnose fatty liver, but it cannot reliably diagnose mild steatosis, and its performance is suboptimal in obese patients. Recently, the controlled attenuation parameter (CAP) was developed as a new test for fatty liver. It is based on the physical phenomenon that the amplitude of ultrasound waves is attenuated more rapidly when they traverse across a steatotic liver. In previous studies, CAP had moderate to good accuracy for fatty liver detection, when compared to histology or magnetic resonance spectroscopy.[9], [10], [11], [12], [13] CAP is measured simultaneously with liver stiffness (LSM) using transient elastography (TE). It is thus possible to diagnose fatty liver and assess the disease severity at the same time.
A TE examination involves 10 measurements, with the median CAP and LSM taken as the estimates for liver fat and fibrosis, respectively, and the interquartile range (IQR) as the dispersion or fluctuation of the measurements. For LSM, the IQR-to-median ratio is a well-recognized parameter for determining the validity of measurement.14 A high IQR-to-median ratio reflects inconsistent results from the 10 measurements and is associated with less accurate results. However, the validity criteria for CAP are undefined. It is therefore difficult for clinicians to interpret CAP results.
In this study, we aim to determine factors associated with less accurate CAP measurements and define the validity criteria for CAP.
Section snippets
Patients
This was a cross-sectional study of a prospective cohort of adult patients aged 18 years or above who underwent liver biopsy for the evaluation of chronic liver diseases at two European centers and one Hong Kong center. We excluded patients with less than 10 successful CAP/LSM acquisitions and those with liver biopsy specimens shorter than 15 mm. The study protocol was approved by all participating centers. All patients provided informed written consent. Part of this cohort (94 patients from Hong
Results
From May 2009 to September 2016, 1,036 patients underwent paired TE and liver biopsy. After excluding patients with suboptimal liver biopsy specimens and TE examination, 754 patients were included in the final analysis (340 from the French cohort, 203 from the Italian cohort, and 211 from the Hong Kong cohort) (Table 1, Fig. S1). The excluded patients were older, more likely to have diabetes, hypertension and high BMI, but had lower albumin, alanine aminotransferase (ALT) and platelet count (
Discussion
CAP is performed together with LSM and can be used to detect fatty liver and assess the degree of liver injury simultaneously and conveniently. However, compared with LSM, the overall accuracy of CAP is lower, with a significant proportion of patients being misclassified.[9], [10], [11], [12], [13], [17] Head-to-head comparisons also showed that CAP is inferior to magnetic resonance imaging-based proton density fat fraction.24 Nevertheless, because of cost and availability, TE will likely
Financial support
This project was partially supported by a grant from the Research Grant Council of the Hong Kong SAR Government (Project no. CUHK 477813).
Conflict of interest
Vincent Wong, Grace Wong, Henry Chan and Victor de Lédinghen have served as speakers for Echosens.
Please refer to the accompanying ICMJE disclosure forms for further details.
Authors’ contributions
Study design: Vincent Wong. Data collection: Vincent Wong, Salvatore Petta, Jean-Baptiste Hiriart, Calogero Cammà, Grace Wong, Fabio Marra, Julien Vergniol, Anthony Chan, Antonino Tuttolomondo, Wassil Merrouche, Brigitte Le Bail, Umberto Arena, Antonio Craxì, Victor de Lédinghen. Data analysis: Vincent Wong.
Administrative support: Henry Chan, Antonio Craxì. Manuscript drafting: Vincent Wong, Salvatore Petta. All authors read and approved the final version of the manuscript.
Acknowledgements
We would like to thank Mr Yee-Kit Tse for his statistical support.
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These authors contributed equally to this work.