Original ContributionControlled Attenuation Parameter (CAP): A Novel VCTE™ Guided Ultrasonic Attenuation Measurement for the Evaluation of Hepatic Steatosis: Preliminary Study and Validation in a Cohort of Patients with Chronic Liver Disease from Various Causes
Introduction
Steatosis results from the accumulation of fatty droplets in the liver cells and can be a result of several causes such as alcohol consumption, viral hepatitis or metabolic dysfunction (obesity, type 2 diabetes, hyperglycemia, hypertriglyceridemia) (Farrell 2004). Its prevalence is high: from 16∼31% in the general population (Nomura et al., 1988, Bellentani et al., 2000, Browning et al., 2004) up to 46% in heavy drinkers (Bellentani et al. 2000), 50∼80% in the obese population (Farrell and Larter 2006) and 86∼96% in severely obese patients (Dixon et al., 2001, Gholam et al., 2007). Steatosis is a reversible and benign condition. However, in many cases, steatosis can be associated with inflammation (steato-hepatitis), which may result in liver fibrosis and might progress to cirrhosis, liver failure or hepatocellular carcinoma (Farrell 2004).
When the cause of steatosis is the result of a metabolic dysfunction, the disease is called nonalcoholic fatty liver disease (NAFLD). In approximately 30% of NAFLD patients, steatosis is associated with liver inflammation leading to a nonalcoholic steato-hepatitis (NASH) (Farrell and Larter 2006), which has a more severe outcome, leading frequently to extensive fibrosis. With the rising epidemic of obesity and metabolic dysfunctions, NAFLD has become over the last two decades a leading cause of chronic liver disease in affluent countries (Farrell and Larter 2006).
Liver biopsy (LB) has traditionally been regarded as the gold standard for steatosis assessment. However, LB has a potential sampling error (Ratziu et al. 2005), is an invasive and often painful procedure and can result in severe complications (Grant and Neuberger 1999). Therefore, the procedure is accepted by patients with some reluctance. Furthermore, it can only be applied in selected subjects and not readily repeated to assess the follow-up of patients. In some cases, NAFLD patients can be identified by asymptomatic elevation of liver enzymes (Farrell 2004), which, however, have a poor specificity (Clark et al. 2002). Recognizing the high prevalence of steatosis, its frequently benign course and the lack of definitive association with liver enzymes changes, the decision for the hepatologist to refer to LB might be difficult, especially in NAFLD patients. Thus, noninvasive techniques are needed to detect and quantify steatosis, especially for the diagnosis and follow-up of NAFLD patients.
Fibroscan® (Echosens, Paris, France) is an ultrasound-based vibration-controlled transient elastography (VCTE™) device used to assess liver elasticity related to liver fibrosis (Sandrin et al. 2003). Fibroscan shows good results for the detection of significant fibrosis and for the diagnosis of cirrhosis in hepatitis C virus (HCV) (Ziol et al. 2005), hepatitis B virus (HBV) (Marcellin et al. 2009), biliary liver disease (Corpechot et al. 2006), alcoholic liver disease (ALD) (Nahon et al. 2008) and NAFLD (Wong et al. 2010).
Knowing that fat affects ultrasound propagation, a novel attenuation parameter has been developed to detect and quantify steatosis. This parameter is based on the ultrasonic properties of the radiofrequency back-propagated signals acquired by the Fibroscan. It is called controlled attenuation parameter (CAP) because it was devised to specifically target the liver. This control is performed by a sophisticated guidance process based on VCTE. Therefore, CAP can be assessed by an operator who does not have any ultrasound imaging skills. Furthermore, CAP has been designed to be immediate, reproducible and operator and machine-independent.
The aim of the present study was first to validate CAP as an estimate of the ultrasonic attenuation and then to show that CAP is a valid tool for the diagnosis of steatosis. To that purpose, performance of CAP for the detection and quantification of steatosis was appraised, taking LB as a reference, in a cohort of patients with chronic liver disease from various causes.
Section snippets
Measurement principle
In the present study, in vivo ultrasonic signals were acquired using the Fibroscan device, which is an ultrasound-based VCTE system used to perform liver stiffness measurement (LSM) (Sandrin et al. 2003). In our study, a complementary physical parameter—ultrasonic attenuation–designated CAP—is assessed simultaneously with LSM using the radiofrequency signals acquired by the Fibroscan.
The VCTE system generates a shear wave longitudinally polarized on the ultrasound axis (Sandrin et al. 2002).
Results on Field II simulations
Several simulations were performed on homogeneous attenuating media, with attenuations values at 3.5 MHz set from 100 to 350 dB.m−1 by 25 dB.m−1 step. Respective CAP values estimated between 25 and 65 mm are given in dB.m−1 in Fig. 3. The root mean square error (RMSE) for attenuation estimation at 3.5 MHz using CAP is equal to 1.98 dB.m−1.
Results on tissue-mimicking phantoms
Acquisitions were performed on the custom-made elasticity phantom and the two layers of the multipurpose ultrasound tissue-mimicking phantom using the
Discussion
In the present study, a novel CAP has been implemented successfully on the Fibroscan, which automatically estimates the ultrasonic attenuation of the liver using a sophisticated guidance process based on VCTE. First, it has been shown in simulated signals and tissue-mimicking phantoms that CAP is actually an estimate of the ultrasonic attenuation at 3.5 MHz, the central frequency of the transducer. Then, in vivo reproducibility of CAP has been assessed (sCV% = 4.5%). Eventually, satisfactory
Acknowledgments
The authors are very grateful to all the expert pathologists who were involved with the study. They would also like to thank Céline Fournier.
References (45)
- et al.
An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group
Hepatology
(1996) - et al.
Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions
Am J Gastroenterol
(1999) - et al.
Nonalcoholic fatty liver disease
Gastroenterology
(2002) - et al.
Transient elastography (FibroScan)
Gastroenterol Clin Biol
(2008) - et al.
Nonalcoholic fatty liver disease: Predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese
Gastroenterology
(2001) An introduction to ROC analysis
Pattern Recong Lett
(2006)- et al.
Magnetic resonance imaging and spectroscopy for quantification of hepatic steatosis: Urgent need for standardization!
J Hepatol
(2009) - et al.
Ultrasound backscatter and attenuation in human liver with diffuse disease
Ultrasound Med Biol
(1999) - et al.
Attenuation of ultrasound in normal liver and diffuse liver disease in vivo
Ultrason Imaging
(1984) - et al.
Assessment of liver fibrosis using transient elastography in patients with alcoholic liver disease
J Hepatol
(2008)