Hepatic Elastography Using Ultrasound Waves Revised Edition of Volume 1

Transient Elastography (TE) is the first ultrasound-based method for fibrosis assessment, developed by Echosens®(France). In order to obtain reliable liver stiffness (LS) measurements by means of TE, the manufacturer recommended that at least 10 valid shots should be obtained. They should have a success rate (SR: the ratio of valid shots to the total number of shots) of at least 60% and an interquartile range (IQR, the difference between the 75th percentile and the 25th percentile, essentially the range of the middle 50% of the data) less than 30% of the median LS value. New quality criteria were proposed by Boursier in which only IQR is taken into consideration. TE fails if no valid shots can be obtained, and is unreliable if fewer than 10 valid shots are obtained. TE failure is correlated with the body mass index, increasing in obese patients. By using the XL probe, the success rate of TE measurements significantly improves. Also, unreliable results are obtained during aminotransferases flares that can lead to an overestimation of fibrosis. The LS upper limit in healthy subjects was estimated to be 5.3 kPa. Several meta-analyses assessed LS measurements by TE as a predictor of fibrosis, cut-offs for F≥2 ranging from 7.2-7.6 kPa and for F=4 from 12.5-17.3 kPa, according to the etiology of chronic liver disease. Several studies have been published regarding the value of TE for predicting the occurrence of cirrhosis complications. The AUROC’s for predicting clinically significant portal hypertension were 0.945 - 0.99, for cut-off values between 13.6 - 21 kPa, while for predicting esophageal bleeding the best cut-offs ranged between 50.7 – 62.7kPa, with AUROC’s 0.73-0.75. European Guidelines recognize TE as a reliable method to evaluate fibrosis.

VTQ (ARFI) elastography is a new method developed in the last 5-6 years for the non-invasive evaluation of liver fibrosis, integrated into a Siemens Acuson ultrasound system. Ten valid measurements are performed in the right liver lobe, a median value is calculated and the result is expressed in meters/second. The AUROC’s range between 0.75-0.85 for predicting significant fibrosis and for predicting cirrhosis between 0.85-0.95. To increase the accuracy of liver cirrhosis diagnosis, the spleen stiffness (SS) assessed by VTQ (ARFI) can be used. VTQ (ARFI) it is a reproducible method (intraclass correlation coefficient ranging from 0.81-0.87), especially in patients with severe fibrosis and cirrhosis. Similar with Transient Elastography (TE), elevated levels of aminotransferases are associated with the increase of liver stiffness (LS) values assessed by VTQ (ARFI). Even if the manufacturer did not recommend the use of technical parameters IQR (interquartile range interval) and SR (success rate) well-known from TE, published data proved that the accuracy of the method significantly increased with the use of these quality parameters. Regarding the prediction of liver cirrhosis complications, especially portal-hypertension, data regarding the usefulness of LS and/or SS are not so solid, but VTQ (ARFI) accuracy can be increased by combining different parameters.

ElastPQ is a newly developed point Shear Waves elastographic method. Only few data, but with promising results, were published until now regarding this technique.

Shear waves elastography is a technique designed to overcome some of the disadvantages of other elastographic techniques. It is based on supersonic share imaging, an ultrasound-based technique used for real-time visualization of soft tissue viscoelastic properties. This technique is based on the combination of a radiation force induced into the tissues by focused ultrasonic beams and a very high frame rate ultrasound imaging sequence able to capture in real time the transient propagation of the resulting shear waves. Shear waves’ propagation induces small tissue displacements which are recorded by the imaging system, and measured using tissue Doppler techniques. 2D-SWE offers as major innovations the ability to measure area and distance ratios, a high spatial resolution and real-time capabilities. The technique produces an image where true local tissue elasticity is displayed in a color map in “real time”. Elasticity is displayed using a color coded image superimposed on a B-mode image. The true elasticity is assessed based on Shear Waves propagation speed into the tissue. Thus the technique permits a quantitative mapping of liver tissue viscoelasticity. The technique was first available on the Aixplorer® system (SuperSonic Imagine, France) and initially was used for the evaluation of breast nodules, of prostate elasticity, for the evaluation of muscle and tendon stiffness and for thyroid disease diagnosis. Published data showed a real value of this method for liver stiffness estimation in patients with chronic hepatitis. It has the advantage that it can be also used in patients with ascites. A similar technique is now available on the Logiq E9 system (General Electric) with promising results.

Real-Time Strain Elastography performed by the Hitachi System (HI-RTE) uses a conventional ultrasound probe to compare and analyze echo signals before and under slight compression. Initially, HI-RTE offers only qualitative results. To overcome this limitation several quantitative methods in RTE have been developed, such as Elastic Ratio, Elastic Index, Elasticity Score and Liver Fibrosis Index (LFI). Despite being the first ultrasound-based elastography technique, HI-RTE has not yet yielded the desired results in the evaluation of liver fibrosis. This lack of performance is a consequence of inconsistency between the ultrasound-systems, methods and data analysis among different research teams. In the past few years, it seems that the technique has become more standardized and the elastographic assessment parameters are already established. The overall results of a meta-analysis suggested that LFI was excellent in diagnosing F≥3 and has moderate accuracy for F≥2 and F=4. However, LFI could not be applied to accurately differentiate F2 versus F0-1 and F=4 versus F0-3. HI-RTE is readily available with the ultrasound machine, is feasible in patients with ascites and inflammation and has promising results for non-invasive liver fibrosis evaluation in patients with chronic viral hepatitis and fatty liver diseases. In the future, a large, prospective, international multicenter study is essential to obtain a further evaluation of the potential diagnostic value of HI-RTE.

Biological tests, elastographic methods alone or in combination can be used for the non-invasive evaluation of chronic liver diseases, in order to increase their value.

Combinations of non-invasive tests were searched for in order to improve the diagnostic performance of significant fibrosis (F≥2) and severe fibrosis/cirrhosis (F3–F4) the most promising being TE and serologic tests. In chronic hepatitis C a clinical management algorithm was proposed, using the combination of TE (FibroScan®) and FibroTest as the first-line tests in the work-up strategy, thus avoiding liver biopsy in most patients (77%). In HBV inactive carriers, the combination of TE and FibroTest allowed the exclusion of significant fibrosis (F≥2) in nearly 80% of cases.

Another useful combination is of two elastographic methods [TE and VTQ (ARFI)], which proved to be highly specific for predicting significant fibrosis (F≥2 Metavir). When both TE and VTQ (ARFI) values were higher than the proposed cut-offs, their combination had 93.3% Sp and 96.8% PPV for predicting F≥2, so that liver biopsy could be avoided in 60.5% of cases. For predicting cirrhosis (F4), the results were also very good, with 94.4% Sp, 94.4% NPV and 91.8% accuracy, so that the combination of TE and VTQ was able to confirm, and also to exclude the presence of liver cirrhosis.

Several elastographic techniques for liver fibrosis assessment are available (on different machines) and practitioners are interested in comparing these techniques with regard to feasibility but also with regard to accuracy in staging fibrosis. Comparative studies including at least three methods are presented in this chapter. Regarding feasibility, the most feasible technique seems to be ElastPQ (approximately 99%), followed by VTQ (approximately 93%) and TE and 2D-SWE (approximately 87%). VTQ, ElastPQ and 2D-SWE had similar accuracies for diagnosing at least significant fibrosis (F≥2) and cirrhosis (F4) considering TE as the reference method.

The accurate characterization and the differential diagnosis between different types of focal liver lesions (FLL) are important aims that all imaging modalities available today should satisfy. Elastographic methods aim to exploit the elasticity differences between FLL and liver parenchyma in order to make the differential diagnosis between malignant and benign lesions. Currently, three elastographic methods have been evaluated and showed their applicability in this area: Acoustic Radiation Force Impulse (ARFI) Elastography, Real-time Elastography (RTE) and Shear Waves Elastography (SWE). Many studies have shown that using one of the elastographic methods, for a chosen cut-off, the differentiation between malignant and benign nodules is possible. Other studies demonstrated that elastographic techniques are helpful to detect recurring hepatocellular carcinomas (HCCs), or to evaluate HCC or liver metastases after local or systemic treatment.

Scientific papers regarding ultrasound based elastographic techniques have been published in great numbers since new elastographic methods are constantly appearing in the market. Thus it is mandatory that professional societies and experts in the field should try to organize the available data in order to assess the clinical usefulness of elastography. In this regard, guidelines were issued by national and international ultrasound societies, as well as by other professional societies. These guidelines are presented in this chapter.

The worldwide prevalence of the hepatitis C virus takes a heavy toll on lives, communities, and health systems. Every year more than 4 million peoples die from hepatitis C-related liver cancers and cirrhosis- a mortality tool comparable to that of HIV and tuberculosis. It needs for a global health sector strategy stems from the scale and complexity of the hepatitis C epidemic, along with growing recognition of its massive public health burden, and the huge opportunities for action. It is a golden time now to establish a coherent public health hepatitis C response that prioritizes effective interventions, promotes service delivery approaches that ensure quality and equity to test and treat every hepatitis C infected individual, takes programs to achieve the sustained impact of hepatitis C diagnostics and therapeutics at the population level, and establishes clear stakeholder responsibility and accountability. There are unprecedented opportunities to act while ending the hepatitis C epidemic and are feasible with the tools and approaches currently available and in the pipeline. For the greatest impact, these opportunities should be combined and tailored for specific populations, locations, and settings. New opportunities and health sector policies provide a ray of hope for the elimination of hepatitis C as a public health threat. In this book chapter, we will highlight the goals, aims, opportunities, and barriers to a coherent public health policy for hepatitis C effective interventions at screening, diagnostic, and therapeutic scale in general and vulnerable hepatitis C infected populations and their consensus implementations to healthcare systems.