Abstract
Accurate assessment of the degree of liver fibrosis is important for estimating prognosis and deciding on an appropriate course of treatment for cases of chronic liver disease (CLD) with various etiologies. Because of the inherent limitations of liver biopsy, there is a great need for non-invasive and reliable tests that accurately estimate the degree of liver fibrosis. Ultrasound (US) elastography is considered a non-invasive, convenient, and precise technique to grade the degree of liver fibrosis by measuring liver stiffness. There are several commercial types of US elastography currently in use, namely, transient elastography, acoustic radiation force impulse imaging, supersonic shear-wave imaging, and real-time tissue elastography. Although the low reproducibility of measurements derived from operator-dependent performance remains a significant limitation of US elastography, this technique is nevertheless useful for diagnosing hepatic fibrosis in patients with CLD. Likewise, US elastography may also be used as a convenient surveillance method that can be performed by physicians at the patients’ bedside to enable the estimation of the prognosis of patients with fatal complications related to CLD in a non-invasive manner.
Roles for Longitudinal Surveillance
To date, the majority of elastography studies have focused on evaluating the cross-sectional performance with respect to the histological fibrosis grade or HVPG. However, an important but undervalued use of elastography is the ability to repeatedly measure liver stiffness. The roles of elastography as longitudinal perspectives with respect to the prediction of the long-term prognosis of the disease and monitoring of clinical courses with or without treatment are well known. In particular, these approaches can be used to non-invasively estimate the prognosis of the patients with fatal complications related to CLD, such as variceal bleeding and decompensation.
A longitudinal follow-up of elastography has been proposed as a way to establish the tailored management strategies by providing more detailed prognostic information [40]. For example, the concept of cirrhosis has recently changed from dynamic to bidirectional. In other words, cirrhosis patients may recover if antiviral therapy can be applied properly. At this time, the ideal approach to assess histological outcomes during treatment is serial liver biopsy; however, this is not possible in most cases. Instead, the measurement of liver stiffness by elastography is very useful for monitoring the changes in liver fibrosis during the antiviral treatment [41,42]. In terms of portal hypertension, elastography may also be used to predict the development of variceal bleeding by using a hybrid parameter, the liver stiffness-spleen diameter to platelet ratio score (LSPS) defined as the product of liver stiffness and the maximum spleen diameter divided by the platelet count [43]. According to risk stratification based on LSPS, a different prophylactic treatment for the prevention of variceal bleeding should be considered for patients with an LSPS value higher than 6.5 points [44].
US Elastography: Weaknesses and Strengths
The most significant challenge facing US elastography is the issue of measurement reproducibility. A number of studies concerning this issue have been published; however, many investigators have brought up questions about this issue due to the inherent limitations of US such as the operator-dependent performance. Transient elastography is a highly reproducible and user-friendly technique [45], and liver stiffness measurement by transient elastography does not require a learning curve: even a novice can obtain a reliable result after a single training session [46]. However, because liver stiffness measurements can be influenced significantly by steatosis, obesity, lower degrees of hepatic fibrosis [45], necroinflammation of hepatocytes [47], cholestasis [48], elevated central venous pressure [49], and even postprandial conditions [50], it should be carefully applied when used as an alternative measurement of liver stiffness instead of liver biopsy.
In the case of ARFI, the overall reproducibility is also not bad, having an intraclass correlation coefficient (ICC) value for the interrater observation of 0.81 and an ICC for the intrarater observation of 0.90. However, gender (women), high body mass index, ascites, and lower degree of liver disease (noncirrhotic patients) are considered factors that impede the reproducibility of ARFI [51]. In the case of SSI, the inter- and intraobserver agreements have ICC values of 0.88 and 0.94, respectively, which are similar to the results of ARFI imaging [52].
Despite the issues described above, US elastography has many advantages in clinical fields. The most important aspect is convenience, as is the case with most ultrasonography examination techniques. Indeed, US elastography is fast, easy to use, and portable, so much so that it can be performed at the patient’s bedside. Likewise, because it does not use ionizing radiation, US elastography is relatively safe, even in patients who repeatedly undergo the procedure. US elastography is also less expensive than MR elastography [53]. Going forward, the most important strength of US elastography is the availability of a large amount of accumulated clinical data that have demonstrated its clinical usefulness, although most of these data are related to transient elastography.
Conclusions
Measurement of liver stiffness using various technical developments is evolving to overcome its limitations. Recently, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) published an informative guideline for the use of US elastography [54,55] that deals with the relevant technology and clinical applications. Along with the basic principles for use, these guidelines include the practical advantages and disadvantages of US elastography as well as recommendations for the examination of various body parts. According to these guidelines, US elastography is useful to assess the severity of liver fibrosis in patients with diffuse liver disease and particularly to distinguish patients with nil to mild fibrosis from those with significant fibrosis, although some of the newer techniques must be validated through clinical studies. At present, however, US elastography for the differentiation of focal hepatic lesions is not recommended.
In conclusion, US elastography is useful for diagnosing hepatic fibrosis in patients with CLD and may be used as a convenient and non-invasive surveillance method to estimate the prognosis of patients with fatal complications related to CLD. Accordingly, the development of a standardized method for liver stiffness measurement and technical improvements should be a priority for the clinical application of US elastography. Together, these efforts will significantly enhance the clinical implications of US elastography.
41. Fung J, Lai CL, Wong DK, Seto WK, Hung I, Yuen MF. Significant changes in liver stiffness measurements in patients with chronic hepatitis B: 3-year follow-up study. J Viral Hepat 2011;18:e200–e205.
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