Original contribution
Transient elastography: a new noninvasive method for assessment of hepatic fibrosis

https://doi.org/10.1016/j.ultrasmedbio.2003.07.001Get rights and content

Abstract

Chronic hepatitis is accompanied by progressive deposit of hepatic fibrosis, which may lead to cirrhosis. Evaluation of liver fibrosis is, thus, of great clinical interest and, up to now, has been assessed with liver biopsy. This work aims to evaluate a new noninvasive device to quantify liver fibrosis: the shear elasticity probe or fibroscan®. This device is based on one-dimensional (1-D) transient elastography, a technique that uses both ultrasound (US) (5 MHz) and low-frequency (50 Hz) elastic waves, whose propagation velocity is directly related to elasticity. The intra- and interoperator reproducibility of the technique, as well as its ability to quantify liver fibrosis, were evaluated in 106 patients with chronic hepatitis C. Liver elasticity measurements were reproducible (standardized coefficient of variation: 3%), operator-independent and well correlated (partial correlation coefficient = 0.71, p < < 0.0001) to fibrosis grade (METAVIR). The areas under the receiver operating characteristic (ROC) curves were 0.88 and 0.99 for the diagnosis of patients with significant fibrosis (≥ F2) and with cirrhosis ( = F4), respectively. The Fibroscan® is a noninvasive, painless, rapid and objective method to quantify liver fibrosis. (E-mail: [email protected])

Introduction

Chronic liver diseases often result in fibrosis that may eventually lead to cirrhosis, a state that carries a risk of lethal complications, including hepatocellular carcinoma. These facts point out the clinical interest in quantifying hepatic fibrosis and detecting patients with cirrhosis. At present, liver biopsy is the “gold standard” method to assess the grade of liver fibrosis. However, the use of liver biopsy has several limitations: physical and mental discomfort of the patients that may lead to a high percent of refusal, nonnegligible morbidity and occasional mortality Cadranel et al., 2000, Poynard et al., 2000. Furthermore, due to the limited size of liver samples and the subjective assessment made by pathologists, accuracy and reproducibility of histologic grading has been questioned Abdi et al., 1979, Maharaj et al., 1986, Soloway et al., 1971. Therefore, there is an increasing need for alternative noninvasive methods to estimate the grade of liver fibrosis (Friedman 2003). Among other potentially interesting approaches, elastography seems to be one of the most promising. Indeed, it is well known that liver stiffness is related to the degree of hepatic fibrosis, and palpation has been used from decades to establish a clinical diagnosis of hepatic fibrosis and cirrhosis. Recently, Yeh et al. (2002) found a correlation between liver elasticity measured on 19 liver samples obtained after hepatectomy and the fibrosis score determined by histologic analysis.

The development of elastographic techniques yielded four major approaches: static elastography, dynamic elastography, transient elastography and remote elastography. Static elastography (Ophir et al. 1991) has been applied to breast in vivo Cespedes et al., 1993, Krouskop et al., 1998 and prostate in vitro (Krouskop et al. 1998). However, the use of this technique is limited by high sensitivity to boundary conditions that would certainly induce artefacts in the so-called elastogram, when applied to organs such as liver that can not be placed under controlled compression in vivo. Among dynamic elastographic techniques, magnetic resonance imaging (MRI) Lorenzen et al., 2003, Muthupillai et al., 1995 has proven efficiency in measuring variations of the breast parenchyma elasticity during menstrual cycles. However, the technique requires long acquisition times that are incompatible with the study of organs moving during respiration, such as liver. Furthermore, the cost of MRI examination is prohibitive. Another dynamic technique termed sonoelasticity or sonoelastography Lerner et al., 1987, Levinson et al., 1995, Parker et al., 1990, Yamakoshi et al., 1987, Yamakoshi et al., 1990 has been applied to in vivo liver elasticity measurements by Sanada et al. (2000) using a specifically adapted commercially available sonographic scanner. They showed that the average velocity of the low-frequency wave was higher among patients with chronic hepatitis or cirrhosis than among healthy volunteers. However, the results are likely to be biased by high boundary condition sensitivity, diffraction effects (Catheline et al. 1999b) and displacements of the liver during acquisition time that lasts about 90 s. More recently, remote elastography Nightingale et al., 2001, Rudenko et al., 1996, Sarvazyan, 1995 was proposed to image tissue elasticity by remotely inducing low-frequency vibrations in the tissues using acoustic radiation force. In vivo breast measurements were obtained with a combination of acoustic radiation force and ultrafast ultrasonic imaging (Bercoff et al. 2003).

In the present paper, we report in vivo liver elasticity measurements using the shear elasticity probe (Sandrin et al. 2002a), a device based on one-dimensional (1-D) transient elastography. The 1-D transient elastography technique is not intended to produce elasticity images because data are collected on the axis of a single-element transducer. However, elasticity images can be obtained with 2-D transient elastography, a technique that requires the use of ultrafast ultrasonic imaging Sandrin et al., 1999, Sandrin et al., 2002a. Transient elastography differs from other US-based elastographic techniques by the kind of mechanical stimulation it relies on. The use of a transient vibration presents several advantages. First, the transmitted elastic wave can be temporally separated from reflected elastic waves. Thus, the technique is less sensitive to boundary conditions than other elastographic techniques. Second, the acquisition time is short (typically less than 100 ms), which enables measurements to be made on moving organs. Transient elastography is, thus, well adapted to the study of the liver.

This work aimed to evaluate the interest of the shear elasticity probe or Fibroscan® in quantifying hepatic fibrosis and detecting cirrhosis in a cohort of patients with hepatitis C virus (HCV) chronic hepatitis. Hepatitis C is a worldwide health problem and hepatic fibrosis grade is a key parameter to assess prognosis and an indication of antiviral treatments in this disease. Furthermore, a semiquantitative score has been developed and validated for this condition (Bedossa and Poynard 1996). It allows comparison between elasticity measurement and histologic fibrosis staging. We evaluated, first, intra- and interoperator reproducibility of the liver elasticity measurement and, second, the ability of elasticity measurements to estimate the degree of hepatic fibrosis.

Section snippets

Patients

Two cohorts of patients with HCV chronic hepatitis participated in the study after giving their informed consent. The intra- and interoperator reproducibility of the measurement technique were investigated in 15 patients. The ability of liver elasticity measurement to quantify hepatic fibrosis was investigated in 91 patients. Criteria for inclusion of patients were the following: 1. well documented HCV chronic hepatitis with the presence of HCV RNA in the serum and elevated serum transaminases

Elasticity measurements

Examples of strain images (strain as a function of depth and time) are plotted in Fig. 5 for different liver fibrosis grades. As shown in Fig. 5. the slope of the wave pattern and, thus, the shear velocity seems to increase as the fibrosis grade increases. This indicates that liver gets harder as fibrosis spreads out. In both population cohorts, elasticity estimates vary from 3.35 to 69.1 kPa, which corresponds to shear wave velocity ranging from 1.06 to 4.80 m/s. Elasticity measurements were

Discussion

Liver elasticity in patients with HCV chronic hepatitis is highly correlated with the degree of liver fibrosis assessed by biopsy. The diagnostic performances of the Fibroscan® are good. Even though the studied population is too limited to define absolute thresholds, the result presented here show that elasticity measurements are promising to split the patients into different subgroups. Patients with cirrhosis or advanced fibrosis, who need to be treated to prevent the evolution to cirrhosis,

Acknowledgements

The authors thank the Laboratoire Ondes et Acoustiques and especially Mathias Fink for his support in their developments at the early beginning of the project.

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