Abstract
The World Federation for Ultrasound in Medicine and Biology has produced these guidelines for the use of elastography techniques in liver diseases. For each available technique, the reproducibility, results and limitations are analyzed, and recommendations are given. This set of guidelines updates the first version, published in 2015. Since the prior guidelines, there have been several advances in technology. The recommendations are based on the international published literature, and the strength of each recommendation is judged according to the Oxford Centre for Evidence-Based Medicine. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of liver diseases.
Key Words
Introduction
Elastography has been used to evaluate liver stiffness for more than 10 y. As chronic liver damage results in hepatic fibrosis, characterized by an increase of extracellular matrix produced by fibroblast-like cells, the liver becomes stiffer than normal. Elastography can be used to assess liver stiffness non-invasively. It measures tissue behavior when an external mechanical actuation or an internal acoustic radiation force is applied and can be monitored by ultrasound (US) or magnetic resonance imaging (MRI).
This document reviews the several US-based elastography techniques available clinically. Magnetic resonance elastography is not discussed but is described elsewhere (
Barr et al., 2016b
). The several US-based elastography techniques have been extensively described in Part 1 (Shiina et al., 2015
). These techniques differ in the physical approaches used and can be grouped into three major types: (i) transient elastography (TE), which uses a mechanical external push; (ii) acoustic radiation force impulse (ARFI) techniques, which use an acoustic internal push; and (iii) strain elastography (SE) technique, which uses frame-to-frame differences (tissue deformation) with stress, caused by pressing the body surface or by internally occurring physiologic motion. The ARFI techniques can be divided into point shear wave elastography (p-SWE) and 2-D shear wave elastography (2-D SWE) techniques. The shear wave-based techniques (TE and ARFI techniques) measure the speed of shear waves in tissues. The shear waves are generated by an external mechanical push in TE or by the push pulse of a focused ultrasound beam in the ARFI techniques. For both of these techniques, the shear wave speed calculated, which is related to liver stiffness, can be converted into kilopascals, the unit of Young's modulus E (3ρv2, where ρ is the tissue density and v is the speed of the shear wave), assuming that the tissue is purely elastic, incompressible, its elastic response is linear and that the tissue density is always 1000 kg/m3. It is important to note that magnetic resonance elastography (MRE) reports the shear modulus in kilopascals and is three times smaller than the Young's modulus used to report the results of the ultrasound techniques (- Shiina T
- Nightingale KR
- Palmeri ML
- Hall TJ
- Bamber JC
- Barr RG
- Castera L
- Choi BI
- Chou YH
- Cosgrove D
- Dietrich CF
- Ding H
- Amy D
- Farrokh A
- Ferraioli G
- Filice C
- Friedrich-Rust M
- Nakashima K
- Schafer F
- Sporea I
- Suzuki S
- Wilson S
- Kudo M
WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 1. Basic principles and terminology.
Ultrasound Med Biol. 2015; 41: 1126-1147
Barr et al., 2016b
).Guidelines on the use of US elastography for the assessment of liver diseases were produced by the World Federation for Ultrasound in Medicine and Biology (WFUMB) a few years ago (
Ferraioli et al., 2015
); however, this is a very rapid growing field and new evidence and improvements are available since that release.- Ferraioli G
- Filice C
- Castera L
- Choi BI
- Sporea I
- Wilson SR
- Cosgrove D
- Dietrich CF
- Amy D
- Bamber JC
- Barr R
- Chou YH
- Ding H
- Farrokh A
- Friedrich-Rust M
- Hall TJ
- Nakashima K
- Nightingale KR
- Palmeri ML
- Schafer F
- Shiina T
- Suzuki S
- Kudo M
WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3.
Liver. Ultrasound Med Biol. 2015; 41: 1161-1179
Our objectives were to determine, based on the evidence from the literature, what is new since the previous release of the WFUMB guidelines (
Ferraioli et al., 2015
), regarding the impact of elastography on reduced use and/or replacement of liver biopsy for diffuse liver diseases. The potential role of elastography in the characterization of focal liver lesions is also discussed.- Ferraioli G
- Filice C
- Castera L
- Choi BI
- Sporea I
- Wilson SR
- Cosgrove D
- Dietrich CF
- Amy D
- Bamber JC
- Barr R
- Chou YH
- Ding H
- Farrokh A
- Friedrich-Rust M
- Hall TJ
- Nakashima K
- Nightingale KR
- Palmeri ML
- Schafer F
- Shiina T
- Suzuki S
- Kudo M
WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3.
Liver. Ultrasound Med Biol. 2015; 41: 1161-1179
The authors met in Chicago in December 2017 to discuss and reach consensus on the use of liver elastography for liver stiffness measurements. Recommendations were made and graded using the Oxford classification, including Level of Evidence (LoE), Grade of Recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [
Oxford Centre for Evidence-Based Medicine 2009
).Terminology, techniques, systems
Transient elastography
Transient elastography is a 1-D technique performed with the FibroScan system (Echosens, Paris, France). The technique has been fully described (
Ferraioli et al., 2015
).- Ferraioli G
- Filice C
- Castera L
- Choi BI
- Sporea I
- Wilson SR
- Cosgrove D
- Dietrich CF
- Amy D
- Bamber JC
- Barr R
- Chou YH
- Ding H
- Farrokh A
- Friedrich-Rust M
- Hall TJ
- Nakashima K
- Nightingale KR
- Palmeri ML
- Schafer F
- Shiina T
- Suzuki S
- Kudo M
WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3.
Liver. Ultrasound Med Biol. 2015; 41: 1161-1179
The newer version of TE, available on the FibroScan 502 Touch system, allows measurement of the decrease in amplitude of ultrasound signal in the liver, using the controlled attenuation parameter (CAP) tool. The CAP results are given in decibels per meter (dB/m), range from 100 to 400 and are related to the amount of fat in the liver. The system has three types of probes with different ultrasound frequencies. The M probe has an ultrasound frequency of 3.5 MHz for measurement at a depth from 2.5 to 6.5 cm from the skin. The XL probe, with an ultrasound frequency of 2.5 MHz for measurement from 3.5 to 7.5 cm, is used when the skin-to-liver capsule distance is >2.5 cm. The software of the system controls the choice between the two probes based on this distance. The S probe, with an ultrasound frequency of 5.0 MHz for measurements between 1.5 and 5.0 cm, is usually used in children, when the thoracic diameter is <75 cm. As of today, CAP is available on the M and XL probes and is displayed only when the liver stiffness measurement (LSM) is valid, because it is computed from the ultrasound signals used for acquiring LSM (
Berzigotti et al., 2018
).Acoustic radiation force impulse techniques
These techniques are based on the generation of shear waves by the push pulse of the ultrasound beam. To generate the tissue displacement, the length of pulse of the US beam is longer than that used for the B-mode image, to provide momentum transfer pushes. The techniques are described in detail elsewhere (
Shiina et al., 2015
).- Shiina T
- Nightingale KR
- Palmeri ML
- Hall TJ
- Bamber JC
- Barr RG
- Castera L
- Choi BI
- Chou YH
- Cosgrove D
- Dietrich CF
- Ding H
- Amy D
- Farrokh A
- Ferraioli G
- Filice C
- Friedrich-Rust M
- Nakashima K
- Schafer F
- Sporea I
- Suzuki S
- Wilson S
- Kudo M
WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 1. Basic principles and terminology.
Ultrasound Med Biol. 2015; 41: 1126-1147
The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) has recently updated the guidelines for the use of elastography in the assessment of liver fibrosis (
Dietrich et al., 2017a
). We agree with that terminology.- Dietrich CF
- Bamber J
- Berzigotti A
- Bota S
- Cantisani V
- Castera L
- Cosgrove D
- Ferraioli G
- Friedrich-Rust M
- Gilja OH
- Goertz RS
- Karlas T
- de Knegt R
- de Ledinghen V
- Piscaglia F
- Procopet B
- Saftoiu A
- Sidhu PS
- Sporea I
- Thiele M
EFSUMB guidelines and recommendations on the clinical use of liver ultrasound elastography, update 2017 (long version).
Ultraschall Med. 2017; 38: e16-e47
Acoustic radiation force impulse-based techniques are available on both the linear and the curvilinear transducers. For assessment of the liver, generally the curvilinear transducer is used (at least in adults). Note that shear wave speeds are dependent on ARFI pulse frequency; therefore, the values will differ if a linear higher-frequency probe is used. Manufacturers have provided quality factors for the measurements (Table 1). These quality factors evaluate if the stiffness value reported meets criteria for an accurate measurement.
Table 1Available equipment
| SWE technique | System (manufacturer) | Software registered name | Quality criteria and/or additional features (manufacturer derived) | Additional tools |
|---|---|---|---|---|
| Transient elastography | FibroScan FibroScan 502 Touch (EchoSens, France) | FibroScan | The software determines automatically whether each measurement is successful or not and controls choice between M+ and XL+ probes based on skin-to-liver capsule distance (this second option is available with the newer systems); 10 measurements and IQR/M ≤30% | Controlled Attenuation Parameter (CAP) to detect and quantify liver steatosis. |
| Point SWE (pSWE) | Acuson S2000 and 3000 (Siemens Healthineers, Germany) | Virtual Touch Quantification (VTQ) | If signal/to noise ratio is low, “XXX” is displayed. | |
| iU22, Epiq series, Affiniti (Philips Healthcare, Netherlands) | ElastPQ | No measurement displayed if signal/to noise ratio is low; for each measurement the standard deviation is provided | ||
| HI-VISION Ascendus, Arietta 70, Arietta 850 (Hitachi Ltd, Japan) | Shear wave measurement (SWM) | No measurement displayed if signal/to noise ratio is low; net amount of effective shear wave velocity (VsN) ≥50% | Combinational elastography (available on the Arietta 850) that combines strain and shear wave elastography. ATT – attenuation software for quantification of liver steatosis. | |
| MyLab 9 (Esaote, Italy) | QElaXto | No measurement displayed if signal/to noise ratio is low; rate of effective measure for each value shown in the screen (H,M,L) | ||
| HS70 A, RS80 A (Samsung Medison, South Korea) | S-shearwave | Reliable measurement index (RMI) | ||
| 2-D SWE | Aixplorer (SuperSonic Imagine, France) | SSI | No color displayed if signal/to noise ratio is low; stability index (SI) | |
| Epiq series (Philips Healthcare, Netherlands) | ElastQ | No color displayed if signal/to noise ratio is low; confidence map | ||
| Acuson S3000 (Siemens Healthineers, Germany) | Virtual Touch IQ | |||
| Logiq E9 (GE Healthcare, USA) | Pixels remain blank if result is not “satisfactory” | |||
| Aplio 500, i-series (Canon Medical Systems, Japan) | Propagation map | Shear wave dispersion imaging, related to tissue viscosity. Attenuation Imaging (ATI) to detect and quantify liver steatosis. | ||
| Resona series, DC-80 system (Mindray, China) | Sound Touch Elastography (STE), Sound Touch Quantification (STQ) | Reliability map (RLB); stability from motion in a period of time frames (M-STB) |
SWE = shear wave elastography
Variability between p-SWE and 2-D SWE systems
Limitations and system differences
The main limitation of these techniques is that different estimates of shear wave speed (SWS) are obtained with different systems.
The Quantitative Imaging Biomarker Alliance (QIBA) committee of the Radiologic Society of North America (RSNA) performed an inter-laboratory study of SWS estimation in elastic phantoms. Commercially available SWE systems were used. A statistically significant difference in SWS estimates among systems and a depth-dependent estimate of SWS for each system were obtained. The inter-system variability ranged from 6% to 12%. No statistically significant differences were found among raters using the same system. The study also reported very good agreement between systems (
Hall et al., 2013
).- Hall TJ
- Milkowski A
- Garra B
- Carson P
- Palmeri M
- Nightingale K
- Lynch T
- Alturki A
- Andre M
- Audiere S
- Bamber J
- Barr R
- Bercoff J
- Bercoff J
- Bernal M
- Brum J
- Chan HW
- Chen S
- Cohen-Bacrie C
- Couade M
- Daniels A
- DeWall R
- Dillman J
- Ehrman R
- Franchi-Abella SF
- Fromageau J
- Gennisson JL
- Henry JP
- Ivancevich N
- Kalin J
- Kohn S
- Kugel J
- Lee K
- Liu NL
- Loupas T
- Mazenik J
- McAleavey S
- Miette V
- Metz S
- Morel BM
- Nelson T
- Nordberg E
- Oudry J
- Padwal M
- Rouze N
- Samir A
- Sandrin L
- Schaccitti J
- Schmitt C
- Shamdasani V
- Song P
- Wang M
- Wear K
- Xie H
- Zhao H
RSNA/QIBA: Shear wave speed as a biomarker for liver fibrosis staging.
in: Proc IEEE Int Ultrason Symp. 2013: 397-400
It was found that in viscoelastic phantoms, the deepest focal depth (7.0 cm) yielded the greatest inter-system variability for each phantom (maximum of 17.7%) as evaluated by the interquartile range (IQR), and the median SWS estimates for the greatest outlier system for each phantom/focal depth combination ranged from 12.7% to 17.6% (
Palmeri et al., 2015
).- Palmeri M
- Nightingale K
- Fielding S
- Rouze N
- Deng Y
- Lynch T
- Chen S
- Song P
- Urban M
- Xie H
- Wear K
- Garra B
- Milkowski A
- Rosenzweig S
- Carson P
- Barr R
- Shamdasani V
- Macdonald M
- Wang M
- Guenette G
- Miyajima Y
- Okamura Y
- Dhyani M
- Samir A
- Hah Z
- McLaughlin G
- Gee A
- Chen Y
- Napolitano D
- McAleavey S
- Obuchowski N
- Hall T
RSNA QIBA ultrasound shear wave speed phase II phantom study in viscoeastic media.
Proc IEEE Int Ultrason Symp. 2015; : 1-4
A study has evaluated the variability of SWS assessed with a p-SWE technique at various depths using different frequencies. In both the phantom and liver, the mean velocities as measured by two probes at the same depth and at different depths differed. The lowest variability in the phantom was at 4 and 5 cm from surface with the convex probe and at 2 cm with a linear probe. In the liver, the depth with lower variability was 4 cm from the skin with a convex probe and at 3 and 4 cm with a linear probe (
Chang et al., 2013
). In another study on 89 chronic hepatitis C virus (HCV)-infected patients, the linear probe gave SWS values higher than those obtained with the convex probe (Potthoff et al., 2013
). This is expected because the SWS is dependent on the ARFI frequency: The higher the ARFI frequency, the higher the SWS.A recent study has evaluated the inter-system and inter-observer variability of LSMs in patients with varying degrees of liver stiffness (
Ferraioli et al., 2018
). The assessment of LSMs was performed using six US systems, four with p-SWE and two with 2-D SWE. The Fibroscan was used as the reference standard. There was an agreement >0.80 for all pairs of systems. The mean difference between the values of the systems with 2-D SWE technique was 1.54 kPa, whereas the maximum mean difference between the values of three of four systems with p-SWE technique was 0.79 kPa. The variability between measurements obtained with different systems was higher in stiffer liver. The range of values obtained with the two 2-D SWE systems paralleled that of the Fibroscan in cases of very stiff liver (>15 kPa), whereas the four systems with a p-SWE technology gave lower values in the higher range of liver stiffness. The intra-patient concordance for all systems was 0.89 (95% confidence interval [CI]: 0.83–0.94). Inter-observer agreement was >0.90.Piscaglia et al., 2017
reported that the correlation between stiffness measurements taken with several systems (including the Fibroscan) in different intercostal spaces was good but not perfect.- Piscaglia F
- Salvatore V
- Mulazzani L
- Cantisani V
- Colecchia A
- Di Donato R
- Felicani C
- Ferrarini A
- Gamal N
- Grasso V
- Marasco G
- Mazzotta E
- Ravaioli F
- Ruggieri G
- Serio I
- Sitouok Nkamgho JF
- Serra C
- Festi D
- Schiavone C
- Bolondi L
Differences in liver stiffness values obtained with new ultrasound elastography machines and Fibroscan: A comparative study.
Dig Liver Dis. 2017; 49: 802-808
Recommendation 1: Cutoffs for staging liver fibrosis are system specific. (LoE 1b, GoR A) (10,0,0)
Technical procedures
For all SWE techniques, adherence to a strict protocol is required (Table 2) (
Barr et al., 2016b
). Patients should be fasting for at least 4 h, as ingestion of food increases blood flow to the liver, increasing its stiffness (Barr et al., 2016b
). Ingestion of food can only increase the liver stiffness, therefore, if patients eat and their stiffness values are normal, they have no or mild fibrosis.Table 2Recommendations for performing liver elastography
| Adherence to a strict protocol is required. |
| Patient should fast for 4 h before examination. |
| Exam should be performed with the patient in the supine or slight left lateral position with the arm raised above the head to increase the intercostal space. |
| Measurements should be taken through an intercostal approach at the location of the best acoustical window. |
| Measurements should be taken 1.5 to 2.0 cm below the liver capsule to avoid reverberation artifact. The optimal location for maximum shear wave generation is 4.0–4.5 cm from the transducer. |
| The transducer should be perpendicular to the liver capsule. |
| Placement of the region of interests should avoid large blood vessels, bile ducts and masses. |
| For transient elastography, the appropriate transducer should be selected based on patient's body habitus. |
| Ten measurements should be obtained from 10 independent images, in the same location, with the median value used for transient elastography and point shear wave elastography techniques. Three or five measurements may be appropriate for 2-D shear wave elastography when a quality assessment parameter is used. |
| The IQR/M (interquartile range/median) should be used as a measure of quality. For kPa measurements the IQR/M should be <0.3 and for m/s it should be <0.15 for an accurate data set. |
Transient elastography
The procedure has been fully described in the previous WFUMB guidelines on liver elastography (
Ferraioli et al., 2015
). The strengths of the TE approach are that it is widely available and a point-of-care technique. Weaknesses are the lack of gray-scale image guidance to determine where the measurement is being obtained, inability to visualize and avoid large vessels and masses at the site of measurement (although these may be generally identified on the time-motion and A-mode), the need for recalibration of the spring in the device at 6- to 12-mo intervals (depending on the type of probe), decreased applicability in cases of obesity and inability to use it in patients with ascites.- Ferraioli G
- Filice C
- Castera L
- Choi BI
- Sporea I
- Wilson SR
- Cosgrove D
- Dietrich CF
- Amy D
- Bamber JC
- Barr R
- Chou YH
- Ding H
- Farrokh A
- Friedrich-Rust M
- Hall TJ
- Nakashima K
- Nightingale KR
- Palmeri ML
- Schafer F
- Shiina T
- Suzuki S
- Kudo M
WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3.
Liver. Ultrasound Med Biol. 2015; 41: 1161-1179
ARFI-based techniques
The procedure has been fully described in the previous guidelines (
Barr et al., 2016b
). These are listed in Table 2.Although most vendors allow measurements to 8 cm from the transducer, measurement accuracy decreases below 6 cm from the transducer because of attenuation of the ARFI pulse.
The literature suggests that 10 measurements should be obtained for p-SWE, and the median value reported. Several studies have indicated that an IQR/median (M) ≤30% (measurements in kPa) improves accuracy in staging liver fibrosis. Recent literature suggests that a smaller number of measurements may be accurate (
Fang et al., 2018
, - Fang C
- Jaffer OS
- Yusuf GT
- Konstantatou E
- Quinlan DJ
- Agarwal K
- Quaglia A
- Sidhu PS
Reducing the number of measurements in liver point shear-wave elastography: Factors that influence the number and reliability of measurements in assessment of liver fibrosis in clinical practice.
Radiology. 2018; 287172104
Ferraioli et al., 2016a
); however, at this time there is not enough literature to support this suggestion. The energy deposition of the ARFI push pulse for U.S. Food and Drug Administration (FDA)-approved vendor systems is within current FDA diagnostic limits for livers in adults. Off-label use for other organs and for use during and immediately after the use of US contrast materials should be avoided until further investigated (Cui et al., 2014
).In 2-D SWE, a larger field of view (FOV) is placed where the elastogram will be obtained. Within that FOV, regions of interest (ROIs) can be placed to obtain the stiffness value. As opposed to p-SWE, the ROI size can be changed. If possible, the ROI should be placed near the center of the FOV, as there are often errors at the borders of the FOV. Most vendors provide the average and the standard deviation of the stiffness values from the pixels in the ROI, and some of them provide the minimum and maximum stiffness values as well. The mean value should be used. The standard deviation within the ROI reports the variability of the pixel measurements within the ROI and is not a measure of the quality of the measurement.
Not enough studies have been performed to provide recommendations, but several studies using 2-D SWE have used three or five measurements if the system has a quality measure that confirms the area of measurement has high-quality shear waves (
Dietrich et al., 2017a
). Most vendors with 2-D SWE may allow the placement of many ROIs within the elastogram FOV. This is discouraged, because if there is an error in that image, the error is reproduced in all the measurements from that image.- Dietrich CF
- Bamber J
- Berzigotti A
- Bota S
- Cantisani V
- Castera L
- Cosgrove D
- Ferraioli G
- Friedrich-Rust M
- Gilja OH
- Goertz RS
- Karlas T
- de Knegt R
- de Ledinghen V
- Piscaglia F
- Procopet B
- Saftoiu A
- Sidhu PS
- Sporea I
- Thiele M
EFSUMB guidelines and recommendations on the clinical use of liver ultrasound elastography, update 2017 (long version).
Ultraschall Med. 2017; 38: e16-e47
Strain elastography
There is no significant change from previous WFUMB liver elastography guidelines (Table 2) (
Ferraioli et al., 2015
).- Ferraioli G
- Filice C
- Castera L
- Choi BI
- Sporea I
- Wilson SR
- Cosgrove D
- Dietrich CF
- Amy D
- Bamber JC
- Barr R
- Chou YH
- Ding H
- Farrokh A
- Friedrich-Rust M
- Hall TJ
- Nakashima K
- Nightingale KR
- Palmeri ML
- Schafer F
- Shiina T
- Suzuki S
- Kudo M
WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3.
Liver. Ultrasound Med Biol. 2015; 41: 1161-1179
A limited study using combinational elastography, the combined use of strain and shear wave imaging with a single machine, might increase accuracy in the diagnosis of liver fibrosis and inflammation (
Yada et al. 2017a
, Yada N1, Tamaki N, Koizumi Y, Hirooka M, Nakashima O, Hiasa Y, Izumi N, Kudo M. Diagnosis of fibrosis and activity by a combined use of strain and shear wave imaging in patients with liver disease. Dig Dis 2017a;35(6):515–520. https://doi.org/10.1159/000480140.
Yada et al. 2017b
). Data mining, which combines SE and serologic tests, is reported to be the novel approach (Yada N1, Sakurai T, Minami T, Arizumi T, Takita M, Hagiwara S, Ida H, Ueshima K, Nishida N, Kudo M. Influence of liver inflammation on liver stiffness measurement in patients with autoimmune hepatitis evaluation by combinational elastography. Oncology 2017b;92 (Suppl) 1:10–15. https://doi.org/10.1159/000451011.
Yada et al., 2014
). In a meta-analysis (Kobayashi et al., 2015
) of 15 studies with 1626 patients, SE was found not to have high accuracy for any cutoff stage of fibrosis.Reproducibility
Shear wave elastography techniques have excellent reproducibility, provided the recommendations of the manufacturer or expert recommendations are followed. For all systems, intra-observer reproducibility assessed with the intra-class correlation coefficient (ICC) was >0.90, and inter-observer reproducibility was >0.80 (
Boursier et al., 2008a
, Fang et al., 2017
, Ferraioli et al., 2012
, Fraquelli et al., 2007
, Garcovich et al., 2017
, Hudson et al., 2013
).Factors that influence the reproducibility of the measurement are similar across the different techniques and are related to the operator's experience and to factors dependent on the subject being examined. A learning curve has been consistently observed not only for TE (
Boursier et al., 2008b
), but also for p-SWE (Fraquelli et al., 2016
) and 2-D SWE (Ferraioli et al., 2012
, Hudson et al., 2013
, Woo et al., 2015
), with higher reproducibility achieved by expert operators.Inter-observer variability increases with higher liver fibrosis stages (
Boursier et al., 2008a
, Fraquelli et al., 2007
, Vuppalanchi et al., 2018
) and in overweight or obese patients (- Vuppalanchi R
- Siddiqui MS
- Van Natta ML
- Hallinan E
- Brandman D
- Kowdley K
- Neuschwander-Tetri BA
- Loomba R
- Dasarathy S
- Abdelmalek M
- Doo E
- Tonascia JA
- Kleiner DE
- Sanyal AJ
- Chalasani N
for the NASH Clinical Research Network
Performance characteristics of vibration-controlled transient elastography for evaluation of non-alcoholic fatty liver disease.
Performance characteristics of vibration-controlled transient elastography for evaluation of non-alcoholic fatty liver disease.
Hepatology. 2018; 67: 134-144
Boursier et al., 2008a
, Fraquelli et al., 2007
). Patient position and respiration phase can affect the results, and variability is decreased by using standardization.Confounding factors and limitations
Although liver fibrosis is the main determinant of liver stiffness, a number of factors have been found to influence LSM, often resulting in a false-positive diagnosis of advanced fibrosis or cirrhosis. Clinicians should be aware of these confounding factors and avoid using liver elastography in such situations. Although most of the studies were conducted using TE for historical reasons, studies using p-SWE or 2-D SWE almost always produced similar effects, suggesting that the same confounders should affect all techniques similarly. Confounding factors were already reported in the previous guidelines (
Barr et al., 2016b
, Dietrich et al., 2017a
, - Dietrich CF
- Bamber J
- Berzigotti A
- Bota S
- Cantisani V
- Castera L
- Cosgrove D
- Ferraioli G
- Friedrich-Rust M
- Gilja OH
- Goertz RS
- Karlas T
- de Knegt R
- de Ledinghen V
- Piscaglia F
- Procopet B
- Saftoiu A
- Sidhu PS
- Sporea I
- Thiele M
EFSUMB guidelines and recommendations on the clinical use of liver ultrasound elastography, update 2017 (long version).
Ultraschall Med. 2017; 38: e16-e47
Ferraioli et al., 2015
). Details on the published studies are available in Supplement 1 (online only). Liver steatosis causes attenuation of the ARFI pulse and can lead to more variability in the measurements, although theoretically it should not affect the SWS, based on current ARFI methods in clinical use, even though some reports have indicated that livers with steatosis have increased viscoelasticity, which can also affect SWS. Published studies have conflicting results.- Ferraioli G
- Filice C
- Castera L
- Choi BI
- Sporea I
- Wilson SR
- Cosgrove D
- Dietrich CF
- Amy D
- Bamber JC
- Barr R
- Chou YH
- Ding H
- Farrokh A
- Friedrich-Rust M
- Hall TJ
- Nakashima K
- Nightingale KR
- Palmeri ML
- Schafer F
- Shiina T
- Suzuki S
- Kudo M
WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3.
Liver. Ultrasound Med Biol. 2015; 41: 1161-1179
RECOMMENDATION 2: The impact of hepatic steatosis on liver stiffness is uncertain. Clinicians should exercise caution when interpreting liver stiffness results in patients with severe steatosis and obesity. (LoE 5, GoR C) (10,0,0)
Viral hepatitis
Hepatitis B
The performance of transient elastography in chronic hepatitis B was described in the last WFUMB guidelines (
Ferraioli et al., 2015
). Since then, 2-D SWE (- Ferraioli G
- Filice C
- Castera L
- Choi BI
- Sporea I
- Wilson SR
- Cosgrove D
- Dietrich CF
- Amy D
- Bamber JC
- Barr R
- Chou YH
- Ding H
- Farrokh A
- Friedrich-Rust M
- Hall TJ
- Nakashima K
- Nightingale KR
- Palmeri ML
- Schafer F
- Shiina T
- Suzuki S
- Kudo M
WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3.
Liver. Ultrasound Med Biol. 2015; 41: 1161-1179
Leung et al., 2013
, - Leung VY
- Shen J
- Wong VW
- Abrigo J
- Wong GL
- Chim AM
- Chu SH
- Chan AW
- Choi PC
- Ahuja AT
- Chan HL
- Chu WC
Quantitative elastography of liver fibrosis and spleen stiffness in chronic hepatitis B carriers: Comparison of shear-wave elastography and transient elastography with liver biopsy correlation.
Radiology. 2013; 269: 910-918
Zeng et al., 2017
) and p-SWE (Hu et al., 2017
, Kim et al., 2016
, Su et al., 2018
) have also been evaluated against liver histology in patients with chronic hepatitis B. Overall, studies have indicated similar diagnostic accuracy across different machines. The accuracy is generally good for the diagnosis of bridging fibrosis and cirrhosis, and it is modest for milder degrees of fibrosis. Two-dimensional SWE and p-SWE also have lower failure rates, especially among obese patients. As currently available antiviral drugs are tolerable and efficacious, the decision to start antiviral therapy can in most cases be made based on serum alanine aminotransferase and hepatitis B virus DNA levels, as well as non-invasive tests of fibrosis (European Association for the Study of the Liver [European Association for the Study of the Liver (EASL) 2017
, Terrault et al., 2018
). Patients with liver stiffness values suggestive of cirrhosis would need surveillance for hepatocellular carcinoma and varices. Liver biopsy is now rarely required outside the research setting.A high serum alanine aminotransferase (ALT) level is one of the major confounding factors for liver stiffness measurement (see Supplement 1 for details). Even patients with mild to moderate ALT elevation to one to five times the upper limit of normal have higher liver stiffness than those with normal ALT levels (
Chan et al., 2009
). Oral nucleos(t)ide analogues effectively suppress hepatic necroinflammation and lead to ALT normalization in the majority of patients with chronic hepatitis B (Wong et al., 2009
). Studies have consistently found that patients can have a significant reduction in liver stiffness during nuleos(t)ide analogue treatment even when there is little or no improvement in histologic fibrosis (Liang et al., 2018
, - Liang X
- Xie Q
- Tan D
- Ning Q
- Niu J
- Bai X
- Chen S
- Cheng J
- Yu Y
- Wang H
- Xu M
- Shi G
- Wan M
- Chen X
- Tang H
- Sheng J
- Dou X
- Shi J
- Ren H
- Wang M
- Zhang H
- Gao Z
- Chen C
- Ma H
- Chen Y
- Fan R
- Sun J
- Jia J
- Hou J
Interpretation of liver stiffness measurement-based approach for the monitoring of hepatitis B patients with antiviral therapy: A 2-year prospective study.
J Viral Hepat. 2018; 25: 296-305
Wong et al., 2011
). The optimal cutoffs for fibrosis and cirrhosis in treated patients are likely to be lower than those in untreated patients, but need to be defined in future studies. In addition, although long-term nucleos(t)ide analogue treatment can reverse histologic cirrhosis (Marcellin et al., 2013
), the risk of hepatocellular carcinoma in such patients is still higher than in those who never had cirrhosis (- Marcellin P
- Gane E
- Buti M
- Afdhal N
- Sievert W
- Jacobson IM
- Washington MK
- Germanidis G
- Flaherty JF
- Schall RA
- Bornstein JD
- Kitrinos KM
- Subramanian GM
- McHutchison JG
- Heathcote EJ
Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: A 5-year open-label follow-up study.
Lancet. 2013; 381: 468-475
Wong et al., 2013
). On the other hand, worsening of portal hypertension and new development of varices should be uncommon during nucleos(t)ide analogue treatment, though the experience is limited to small-cohort studies (Lampertico et al., 2015
). Until further data are available, it is premature to recommend a change in surveillance strategies in cirrhotic patients treated with nucleos(t)ide analogues based on changes in liver stiffness.- Lampertico P
- Invernizzi F
- Vigano M
- Loglio A
- Mangia G
- Facchetti F
- Primignani M
- Jovani M
- Iavarone M
- Fraquelli M
- Casazza G
- de Franchis R
- Colombo M
The long-term benefits of nucleos(t)ide analogs in compensated HBV cirrhotic patients with no or small esophageal varices: A 12-year prospective cohort study.
J Hepatol. 2015; 63: 1118-1125
RECOMMENDATION 3: SWE is useful to exclude significant fibrosis and diagnose cirrhosis in patients with untreated chronic hepatitis B. (LoE 1a, GoR A) (10,0,0)
RECOMMENDATION 4: Liver stiffness usually decreases during antiviral treatment with analogues. Screening for hepatocellular carcinoma and portal hypertension should continue despite decrease liver stiffness in patients with advanced disease (LoE 1b, GoR A) (10,0,0)
Hepatitis C
The current recommendations for treatment of HCV vary significantly between countries and health care systems, according to the availability of therapy. In the absence of universal access to direct-acting antiviral agents (DAAs), as a consequence of high cost, different countries have implemented strategies to prioritize patients for treatment based on disease stage. In that respect, SWE can be used as the first-line investigation for the prioritization of HCV patients for DAAs (
Dietrich et al., 2017b
, - Dietrich CF
- Bamber J
- Berzigotti A
- Bota S
- Cantisani V
- Castera L
- Cosgrove D
- Ferraioli G
- Friedrich-Rust M
- Gilja OH
- Goertz RS
- Karlas T
- de Knegt R
- de Ledinghen V
- Piscaglia F
- Procopet B
- Saftoiu A
- Sidhu PS
- Sporea I
- Thiele M
EFSUMB guidelines and recommendations on the clinical use of liver ultrasound elastography, update 2017 (short version).
Ultraschall Med. 2017; 38: 377-394
European Association for the Study of the Liver (EASL) 2015a
, European Association for the Study of the Liver (EASL)–Asociacion Latinoamericana para el Estudio del Higado (ALEH) 2015b
; EASL–ALEH 2015). The most important endpoint is the presence of cirrhosis as these patients are still at risk (although much lower) of developing liver-related complications, such as portal hypertension and hepatocellular carcinoma (HCC) (Di Marco et al., 2016
, Nahon et al., 2017
, - Nahon P
- Bourcier V
- Layese R
- Audureau E
- Cagnot C
- Marcellin P
- Guyader D
- Fontaine H
- Larrey D
- De Ledinghen V
- Ouzan D
- Zoulim F
- Roulot D
- Tran A
- Bronowicki JP
- Zarski JP
- Leroy V
- Riachi G
- Cales P
- Peron JM
- Alric L
- Bourliere M
- Mathurin P
- Dharancy S
- Blanc JF
- Abergel A
- Serfaty L
- Mallat A
- Grange JD
- Attali P
- Bacq Y
- Wartelle C
- Dao T
- Benhamou Y
- Pilette C
- Silvain C
- Christidis C
- Capron D
- Bernard-Chabert B
- Zucman D
- Di Martino V
- Thibaut V
- Salmon D
- Ziol M
- Sutton A
- Pol S
- Roudot-Thoraval F
ANRS CO12 CirVir Group
Eradication of hepatitis C virus infection in patients with cirrhosis reduces risk of liver and non-liver complications.
Eradication of hepatitis C virus infection in patients with cirrhosis reduces risk of liver and non-liver complications.
Gastroenterology. 2017; 152 (.e142): 142-156
van der Meer et al., 2017
, - van der Meer AJ
- Feld JJ
- Hofer H
- Almasio PL
- Calvaruso V
- Fernandez-Rodriguez CM
- Aleman S
- Ganne-Carrie N
- D'Ambrosio R
- Pol S
- Trapero-Marugan M
- Maan R
- Moreno-Otero R
- Mallet V
- Hultcrantz R
- Weiland O
- Rutter K
- Di Marco V
- Alonso S
- Bruno S
- Colombo M
- de Knegt RJ
- Veldt BJ
- Hansen BE
- Janssen HL
Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication.
J Hepatol. 2017; 66: 485-493
Yada et al., 2016
), after HCV eradication. Thus, they require regular follow-up.RECOMMENDATION 5: SWE is the preferred method as the first-line assessment for the severity of liver fibrosis in untreated patients with chronic viral hepatitis C. It is useful to rule out advanced disease. (LoE 1a, GoR A) (10,0,0)
Role of elastography during antiviral treatment (monitoring)
Most data available on the usefulness of liver stiffness monitoring during antiviral therapy have been obtained with TE. Monitoring of liver stiffness during antiviral treatment with interferon-based therapies has not been considered clinically meaningful (
Hezode et al., 2011
, Yada et al., 2014
) and has not been recommended by guidelines (Ferraioli et al., 2015
). Data in patients treated with DAAs suggest that liver stiffness rapidly declines during treatment, even in patients with advanced fibrosis and cirrhosis (- Ferraioli G
- Filice C
- Castera L
- Choi BI
- Sporea I
- Wilson SR
- Cosgrove D
- Dietrich CF
- Amy D
- Bamber JC
- Barr R
- Chou YH
- Ding H
- Farrokh A
- Friedrich-Rust M
- Hall TJ
- Nakashima K
- Nightingale KR
- Palmeri ML
- Schafer F
- Shiina T
- Suzuki S
- Kudo M
WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3.
Liver. Ultrasound Med Biol. 2015; 41: 1161-1179
Chan et al., 2018
, Facciorusso et al., 2018
, - Facciorusso A
- Del Prete V
- Turco A
- Buccino RV
- Nacchiero MC
- Muscatiello N
Long-term liver stiffness assessment in HCV patients undergoing antiviral therapy: Results from a 5-year cohort study.
J Gastroenterol Hepatol. 2018; https://doi.org/10.1111/jgh.14008
Knop et al., 2016
, Ogasawara et al., 2018
, - Ogasawara N
- Kobayashi M
- Akuta N
- Kominami Y
- Fujiyama S
- Kawamura Y
- Sezaki H
- Hosaka T
- Suzuki F
- Saitoh S
- Suzuki Y
- Arase Y
- Ikeda K
- Kobayashi M
- Kumada H
Serial changes in liver stiffness and controlled attenuation parameter following direct-acting antiviral therapy against hepatitis C virus genotype 1b.
J Med Virol. 2018; 90: 313-319
Persico et al., 2018
, Pons et al., 2017
, Sporea et al., 2017
). This decline appears to reflect the reduction in liver inflammation, like an effect of HCV eradication. However, given the short duration of treatment with DAAs (12 wk) and the high sustained virologic response (SVR) rates (>90%), monitoring of liver stiffness during treatment does not appear clinically relevant.Role of elastography after treatment (monitoring in follow-up)
Although it is tempting to monitor liver stiffness, in cirrhotic patients after SVR, based on the currently available evidence, liver stiffness decrease cannot be used as a surrogate of cirrhosis regression. Therefore, no recommendation can be made at this stage on cutoffs and the time interval to identify cirrhosis regression.
A detailed discussion is presented in Supplement 2 (online only).
RECOMMENDATION 6: Liver stiffness decreases significantly after sustained virological response to treatment with interferon-based therapies or direct-acting antiviral agents. However, liver stiffness cannot be used to stage liver fibrosis or rule out cirrhosis, given the loss of accuracy of cutoffs defined in viremic patients. Screening for hepatocellular carcinoma and portal hypertension should continue despite decrease in liver stiffness in patients with advanced disease. (LoE 1b, GoR A) (10,0,0)
Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis
Non-alcoholic fatty liver disease (NAFLD) is becoming the most common cause of chronic liver disease and a risk factor for HCC (
Dyson et al., 2014
).Transient elastography
Several studies have reported the performance of TE in the assessment of liver fibrosis in NAFLD patients. A recent large meta-analysis (
Xiao et al., 2017
) has reported that, with the M probe, the cutoff for advanced fibrosis ranged from 7.6 to 9 kPa in 14 studies including 2697 patients, with 83% to 89% sensitivity and 77% to 78% specificity. For the XL probe, the cutoff ranged from 5.7 to 9.3 kPa in three studies including 579 patients, with 75% sensitivity and 74% specificity. In a multicenter study (Petta et al., 2015
) of NAFLD patients with liver biopsy data, the cutoff values were 6.9 kPa for F ≥ 2 and 8.4 kPa for F ≥ 3. In this study, the presence of severe liver steatosis was associated with higher LSMs in patients with low-grade fibrosis, leading to the overestimation of liver fibrosis. Therefore, in NAFLD patients, severe steatosis could be a confounding factor (- Petta S
- Vanni E
- Bugianesi E
- Di Marco V
- Camma C
- Cabibi D
- Mezzabotta L
- Craxi A
The combination of liver stiffness measurement and NAFLD fibrosis score improves the noninvasive diagnostic accuracy for severe liver fibrosis in patients with nonalcoholic fatty liver disease.
Liver Int. 2015; 35: 1566-1573
Petta et al., 2015
).- Petta S
- Vanni E
- Bugianesi E
- Di Marco V
- Camma C
- Cabibi D
- Mezzabotta L
- Craxi A
The combination of liver stiffness measurement and NAFLD fibrosis score improves the noninvasive diagnostic accuracy for severe liver fibrosis in patients with nonalcoholic fatty liver disease.
Liver Int. 2015; 35: 1566-1573
In almost all studies, obesity was the major reason for unreliable LSMs; however, the use of the M probe seems the major limitation, leading to higher LSMs and a higher false-positive rate. This limitation is somewhat overcome by using the XL probe (
Friedrich-Rust et al., 2010
, Wong et al., 2010
). It has been reported that the XL probe gives cutoff values 1.5–2 kPa lower than that obtained with the M probe. In a study that compared the M and XL probes (Wong et al., 2012
) on 155 patients, the measurements with M and XL probes correlated well with each other, r = 0.95, but with the XL probe, the LSMs were lower.It has therefore been suggested that different cutoff values be used for different probes. For the M probe, with a 90% sensitivity and specificity to rule in or rule out significant fibrosis, advanced fibrosis and cirrhosis, the cutoff values were 5.8 and 9.0 kPa, 7.9 and 9.6 kPa, and 10.3 and 11.5 kPa, respectively (
Wong et al., 2010
). For the XL probe, with a 90% sensitivity and specificity to rule-in or rule-out significant fibrosis, advanced fibrosis and cirrhosis, the cutoff values were 4.8 and 8.2 kPa, 5.7 and 9.3 kPa and 7.2 and 11.0 kPa, respectively (Wong et al., 2012
).Point shear wave elastography
Few studies have addressed the value of p-SWE for liver fibrosis in NAFLD/non-alcoholic steatohepatitis (NASH) (
Cassinotto et al., 2013
, - Cassinotto C
- Lapuyade B
- Ait-Ali A
- Vergniol J
- Gaye D
- Foucher J
- Bailacq-Auder C
- Chermak F
- Le Bail B
- de Ledinghen V
Liver fibrosis: Noninvasive assessment with acoustic radiation force impulse elastography—Comparison with FibroScan M and XL probes and FibroTest in patients with chronic liver disease.
Radiology. 2013; 269: 283-292
Fierbinteanu Braticevici et al., 2013
, Friedrich-Rust et al., 2012
, Liu et al., 2015b
, Osaki et al., 2010
, Yoneda et al., 2010
). The most recent is a systematic review with meta-analysis, but the article did not provide the optimal cutoff values, and only reported that the p-SWE technique had good performance (area under the receiver operating characteristic curve [AUROC] = 0.89, sensitivity = 80%) (Liu et al., 2015b
).2-D shear wave elastography
Three studies available in the literature report the performance of 2-D SWE (
Cassinotto et al., 2016
, - Cassinotto C
- Boursier J
- de Ledinghen V
- Lebigot J
- Lapuyade B
- Cales P
- Hiriart JB
- Michalak S
- Bail BL
- Cartier V
- Mouries A
- Oberti F
- Fouchard-Hubert I
- Vergniol J
- Aube C
Liver stiffness in nonalcoholic fatty liver disease: A comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy.
Hepatology. 2016; 63: 1817-1827
Herrmann et al., 2018
, - Herrmann E
- de Ledinghen V
- Cassinotto C
- Chu WC
- Leung VY
- Ferraioli G
- Filice C
- Castera L
- Vilgrain V
- Ronot M
- Dumortier J
- Guibal A
- Pol S
- Trebicka J
- Jansen C
- Strassburg C
- Zheng R
- Zheng J
- Francque S
- Vanwolleghem T
- Vonghia L
- Manesis EK
- Zoumpoulis P
- Sporea I
- Thiele M
- Krag A
- Cohen-Bacrie C
- Criton A
- Gay J
- Deffieux T
- Friedrich-Rust M
Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis.
Hepatology. 2018; 67: 260-272
Zheng et al., 2015
). The most recent is a meta-analysis with individual patient data that proposed a cutoff value for diagnosing significant fibrosis (F ≥ 2): >7.1 kPa (AUROC = 0.85) (Herrmann et al., 2018
).- Herrmann E
- de Ledinghen V
- Cassinotto C
- Chu WC
- Leung VY
- Ferraioli G
- Filice C
- Castera L
- Vilgrain V
- Ronot M
- Dumortier J
- Guibal A
- Pol S
- Trebicka J
- Jansen C
- Strassburg C
- Zheng R
- Zheng J
- Francque S
- Vanwolleghem T
- Vonghia L
- Manesis EK
- Zoumpoulis P
- Sporea I
- Thiele M
- Krag A
- Cohen-Bacrie C
- Criton A
- Gay J
- Deffieux T
- Friedrich-Rust M
Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis.
Hepatology. 2018; 67: 260-272
One study compared three elastographic methods (TE, p-SWE and 2-D SWE) in NAFLD patients (
Cassinotto et al., 2014
). For significant fibrosis , 2-D SWE was superior to p-SWE, and for severe fibrosis and cirrhosis, all methods had similar performance. In a large meta-analysis (- Cassinotto C
- Lapuyade B
- Mouries A
- Hiriart JB
- Vergniol J
- Gaye D
- Castain C
- Le Bail B
- Chermak F
- Foucher J
- Laurent F
- Montaudon M
- De Ledinghen V
Non-invasive assessment of liver fibrosis with impulse elastography: Comparison of Supersonic Shear Imaging with ARFI and FibroScan®.
J Hepatol. 2014; 61: 550-557
Xiao et al., 2017
), 2-D SWE had higher diagnostic accuracy than TE and laboratory fibrosis scores in staging fibrosis.RECOMMENDATION 7: SWE can be used for liver stiffness assessment in NAFLD patients to rule out advanced fibrosis and select patients for further assessment. (LoE 1a, GoR A) (10,0,0)
Alcoholic liver disease
Chronic, excessive alcohol consumption can lead to a large spectrum of damage, from liver steatosis to liver cirrhosis (
MacSween and Burt, 1986
). The risk of developing cirrhosis starts with 30 g ethanol/d and increases with increasing daily intake. Also, drinking multiple different alcoholic beverages can increase the risk of developing ALD (Bellentani et al., 1997
). Other studies have found that the risk ratio increases significantly with daily consumption of 20–40 g ethanol/d in women and >80 g ethanol/d in men (Stewart and Day, 2011
; O'Shea, 2010
).Assessment of liver fibrosis
It is important to identify patients with advanced fibrosis who are at risk of developing decompensated liver cirrhosis and HCC. Unfortunately, there are few studies published in the literature.
Transient elastography
There are several studies that reported that TE can be used in patients with ALD, with good performance; however, they report different cutoff values (
Anastasiou et al., 2010
, Bardou-Jacquet et al., 2013
, Boursier et al., 2009
, de Ledinghen et al., 2012b
, Dolman et al., 2013
, Janssens et al., 2010
, Kim et al., 2009
, Lannerstedt et al., 2013
, Lemoine et al., 2008
, - Lemoine M
- Katsahian S
- Ziol M
- Nahon P
- Ganne-Carrie N
- Kazemi F
- Grando-Lemaire V
- Trinchet JC
- Beaugrand M
Liver stiffness measurement as a predictive tool of clinically significant portal hypertension in patients with compensated hepatitis C virus or alcohol-related cirrhosis.
Aliment Pharmacol Ther. 2008; 28: 1102-1110
Mueller et al., 2010
, Nahon et al., 2008
, Nguyen-Khac et al., 2008
, - Nguyen-Khac E
- Chatelain D
- Tramier B
- Decrombecque C
- Robert B
- Joly JP
- Brevet M
- Grignon P
- Lion S
- Le Page L
- Dupas JL
Assessment of asymptomatic liver fibrosis in alcoholic patients using fibroscan: Prospective comparison with seven non-invasive laboratory tests.
Aliment Pharmacol Ther. 2008; 28: 1188-1198
Thiele et al., 2016
, Thiele et al., 2018
, Voican et al., 2017
). A Cochrane review summarized these studies (- Voican CS
- Louvet A
- Trabut JB
- Njike-Nakseu M
- Dharancy S
- Sanchez A
- Corouge M
- Lamouri K
- Lebrun A
- Balian A
- Prevot S
- Lachgar M
- Maitre S
- Agostini H
- Mathurin P
- Perlemuter G
- Naveau S
Transient elastography alone and in combination with FibroTest® for the diagnosis of hepatic fibrosis in alcoholic liver disease.
Liver Int. 2017; 37: 1697-1705
Pavlov et al., 2015
) and reported that for diagnosing significant fibrosis, the optimal cutoff value were around 7.5 kPa, with 94% sensitivity and 89% specificity. For severe fibrosis, a cutoff value of 9.5 kPa (range: 8–11 kPa) gave 92% sensitivity and 70% specificity. For liver cirrhosis, the optimal cutoff value was 12.5 kPa, with 95% sensitivity and 71% specificity (Pavlov et al., 2016
).Point shear wave elastography
There are three studies in the literature on liver fibrosis assessment with p-SWE. One study (
Liu et al., 2015a
) reported only that the correlation between p-SWE and liver biopsy is good (r = 0.71). The other two studies (Kiani et al., 2016
, Zhang et al., 2015
), in which liver biopsy was also performed, gave different cutoff values. This may have occurred because the two studies had smaller and different numbers of patients.2-D shear wave elastography
There are limited studies in the literature on the use of 2-D SWE in ALD (
Thiele et al., 2016
).When is the best time to assess liver fibrosis in ALD patients?
Four studies reported that liver stiffness decreases significantly after patients stopped alcohol abuse (
Bardou-Jacquet et al., 2013
, Gelsi et al., 2011
, Mueller et al., 2010
, Trabut et al., 2012
). Another study found that it is better to scan the patients when they have AST values <100 U/L (Mueller et al., 2015
). Measurements are more accurate if performed after a period of abstinence (Bardou-Jacquet et al., 2013
, Gianni et al., 2017
)Recommendation 8: SWE can be used for liver stiffness assessment in patients with ALD to rule out advanced disease. Caution is needed in patients with ongoing alcohol abuse or with acute alcoholic hepatitis. (LoE 2a, GoE B) (10,0,0)
Other etiologies
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of unknown origin. Hepatic fibrosis may progress despite immunosuppressive treatment (
Manns et al., 2010
). Approximately one-third of patients already have established cirrhosis at diagnosis. According to the International Autoimmune Hepatitis Group, the diagnosis of AIH is based on a combination of biochemical, immunologic and histologic features and the exclusion of viral hepatitis (Hennes et al., 2008
). No generally accepted characteristic imaging features of AIH have been described.- Hennes EM
- Zeniya M
- Czaja AJ
- Pares A
- Dalekos GN
- Krawitt EL
- Bittencourt PL
- Porta G
- Boberg KM
- Hofer H
- Bianchi FB
- Shibata M
- Schramm C
- Eisenmann de Torres B
- Galle PR
- McFarlane I
- Dienes HP
- Lohse AW
International Autoimmune Hepatitis G. Simplified criteria for the diagnosis of autoimmune hepatitis.
Hepatology. 2008; 48: 169-176
AIH patients tend to have higher LSM cutoff values using TE (
Abdalla et al., 2009
, Fitzpatrick et al., 2013
, Guo et al., 2017
, Sagir et al., 2008
, Wang et al., 2011
, Xu et al., 2017b
), p-SWE (Bota et al., 2013
, - Bota S
- Sporea I
- Peck-Radosavljevic M
- Sirli R
- Tanaka H
- Iijima H
- Saito H
- Ebinuma H
- Lupsor M
- Badea R
- Fierbinteanu-Braticevici C
- Petrisor A
- Friedrich-Rust M
- Sarrazin C
- Takahashi H
- Ono N
- Piscaglia F
- Marinelli S
- D'Onofrio M
- Gallotti A
- Salzl P
- Popescu A
- Danila M
The influence of aminotransferase levels on liver stiffness assessed by acoustic radiation force impulse elastography: A retrospective multicentre study.
Dig Liver Dis. 2013; 45: 762-768
Efe et al., 2015
, Righi et al., 2012
) and 2-D SWE (Sun et al., 2016
), compared with patients with HCV and other etiologies. This could be explained by concomitant inflammatory activity, which can increase liver stiffness. TE can predict the grade of fibrosis in treated AIH patients (Anastasiou et al., 2016
, Hartl et al., 2016
, Sporea et al., 2013
), with better results after 6 mo than at earlier time points (Hartl et al., 2016
).There is some preliminary evidence suggesting that primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) have prognostic significance for LSM (
Corpechot et al., 2012
, Corpechot et al., 2014
).- Corpechot C
- Gaouar F
- El Naggar A
- Kemgang A
- Wendum D
- Poupon R
- Carrat F
- Chazouilleres O
Baseline values and changes in liver stiffness measured by transient elastography are associated with severity of fibrosis and outcomes of patients with primary sclerosing cholangitis.
Gastroenterology. 2014; 146 (quiz e915–e976): 970-979
There is insufficient evidence to make a recommendation on the use of SWE for liver stiffness assessment in patients with autoimmune, cholestatic and genetic liver diseases.
Cirrhosis and its complications
For the diagnosis of cirrhosis there are no major changes from the previous guidelines (
Ferraioli et al., 2015
). In patients with advanced chronic liver disease/compensated cirrhosis, LSM is significantly and positively correlated with the hepatic venous pressure gradient (HVPG, “gold standard” method for portal hypertension in cirrhosis).- Ferraioli G
- Filice C
- Castera L
- Choi BI
- Sporea I
- Wilson SR
- Cosgrove D
- Dietrich CF
- Amy D
- Bamber JC
- Barr R
- Chou YH
- Ding H
- Farrokh A
- Friedrich-Rust M
- Hall TJ
- Nakashima K
- Nightingale KR
- Palmeri ML
- Schafer F
- Shiina T
- Suzuki S
- Kudo M
WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3.
Liver. Ultrasound Med Biol. 2015; 41: 1161-1179
Most data available concern TE. With this technique, LSM and HVPG yield a correlation coefficient of 0.55–0.86 (
Berzigotti, 2017
). Even if an accurate estimation of the HVPG value cannot be achieved using LSM, LSM accurately discriminates between patients with and without clinically significant portal hypertension (CSPH, defined as HVPG ≥10 mm Hg, threshold for the appearance of complications); the summary AUROC is 0.93 according to a meta-analysis (You et al., 2017
). It should be underlined that most of the patients included in the studies that correlated HVPG with LSMs had viral or alcoholic cirrhosis, and evidence regarding other etiologies remains limited. In untreated viral cirrhosis, LSM values >20–25 kPa are highly specific for CSPH (You et al., 2017
). Values of LSM >20 kPa remain associated with the presence of CSPH in patients with HCV-related cirrhosis who achieved SVR with DAAs (Lens et al., 2017
); importantly, the decrease in LSM to lower values after SVR does not exclude CSPH, and therefore, clinical follow-up should be continued irrespective of the value of LSM in this population (- Lens S
- Alvarado E
- Marino Z
- Londono MC
- LLop E
- Martinez J
- Fortea JI
- Ibanez L
- Ariza X
- Baiges A
- Gallego A
- Banares R
- Puente A
- Albillos A
- Calleja JL
- Torras X
- Hernandez-Gea V
- Bosch J
- Villanueva C
- Forns X
- Garcia-Pagan JC
Effects of all-oral anti-viral therapy on HVPG and systemic hemodynamics in patients with hepatitis C virus-associated cirrhosis.
Gastroenterology. 2017; 153 (.e1): 1273-1283
Lens et al., 2017
).- Lens S
- Alvarado E
- Marino Z
- Londono MC
- LLop E
- Martinez J
- Fortea JI
- Ibanez L
- Ariza X
- Baiges A
- Gallego A
- Banares R
- Puente A
- Albillos A
- Calleja JL
- Torras X
- Hernandez-Gea V
- Bosch J
- Villanueva C
- Forns X
- Garcia-Pagan JC
Effects of all-oral anti-viral therapy on HVPG and systemic hemodynamics in patients with hepatitis C virus-associated cirrhosis.
Gastroenterology. 2017; 153 (.e1): 1273-1283
High LSM values are also significantly associated with the presence and size of gastroesophageal varices, with summary AUROCs of 0.78–0.84 (
Berzigotti, 2017
). Platelet count and spleen size significantly improve the prediction of varices, obtained by LSM alone (Berzigotti et al., 2013
). It has been reported that compensated patients with values of LSM <20 kPa and normal platelet counts (>150 G/L) bear a very low risk of varices requiring treatment (large varices or varices with red signs) (Abraldes et al., 2016
). These criteria have been recommended by the Baveno VI consensus conference on portal hypertension as a rule, to eliminate unnecessary endoscopies (de Franchis and Baveno, 2015
). Since the publication of the recommendation, several studies have confirmed that these criteria are safe (0–3% of varices needing treatment are missed), but very conservative, allowing endoscopy to be spared in only 15% to 30% of patients with compensated cirrhosis (Marot et al., 2017
). Expanded criteria have recently been proposed by a multicentric consortium; an LSM <25 kPa and platelet count >110 g/L might be used safely, eliminating a larger proportion of endoscopies (32% vs. 14%) (Augustin et al., 2017
).Data regarding LSMs by p-SWE and 2-D SWE in this field remain limited.
Point SWE has been used in three studies addressing the diagnosis of CSPH (
Attia et al., 2015
, Salzl et al., 2014
, - Salzl P
- Reiberger T
- Ferlitsch M
- Payer BA
- Schwengerer B
- Trauner M
- Peck-Radosavljevic M
- Ferlitsch A
Evaluation of portal hypertension and varices by acoustic radiation force impulse imaging of the liver compared to transient elastography and AST to platelet ratio index.
Ultraschall Med. 2014; 35: 528-533
Takuma et al., 2016b
b) and reporting excellent applicability and very good diagnostic accuracy (AUROC: 0.82 – 0.90). Point SWE has been used in a few studies addressing the diagnosis and severity of esophageal varices. Liver stiffness was higher in patients with esophageal varices of any size and was even higher in patients with large varices (Attia et al., 2015
, Salzl et al., 2014
), However, reliable cutoffs are not available yet. No strong recommendation regarding the cutoffs to be used can be made because of the limited evidence.- Salzl P
- Reiberger T
- Ferlitsch M
- Payer BA
- Schwengerer B
- Trauner M
- Peck-Radosavljevic M
- Ferlitsch A
Evaluation of portal hypertension and varices by acoustic radiation force impulse imaging of the liver compared to transient elastography and AST to platelet ratio index.
Ultraschall Med. 2014; 35: 528-533
Two-dimensional SWE has been tested for the diagnosis of CSPH in four studies and a further small series (
Choi et al., 2014
, Elkrief et al., 2015
, - Elkrief L
- Rautou PE
- Ronot M
- Lambert S
- Dioguardi Burgio M
- Francoz C
- Plessier A
- Durand F
- Valla D
- Lebrec D
- Vilgrain V
- Castera L
Prospective comparison of spleen and liver stiffness by using shear-wave and transient elastography for detection of portal hypertension in cirrhosis.
Radiology. 2015; 275: 589-598
Jansen et al., 2016a
, - Jansen C
- Bogs C
- Verlinden W
- Thiele M
- Moller P
- Gortzen J
- Lehmann J
- Praktiknjo M
- Chang J
- Krag A
- Strassburg CP
- Francque S
- Trebicka J
Algorithm to rule out clinically significant portal hypertension combining shear-wave elastography of liver and spleen: A prospective multicentre study.
Gut. 2016; 65: 1057-1058
Kim et al., 2015
, Procopet et al., 2015
). The accuracy of the method was reliable in all of the published studies (AUROC: 0.80 – 0.92). Two studies performed a head-to-head comparison between LSMs obtained by TE and 2-D SWE (Elkrief et al., 2015
, - Elkrief L
- Rautou PE
- Ronot M
- Lambert S
- Dioguardi Burgio M
- Francoz C
- Plessier A
- Durand F
- Valla D
- Lebrec D
- Vilgrain V
- Castera L
Prospective comparison of spleen and liver stiffness by using shear-wave and transient elastography for detection of portal hypertension in cirrhosis.
Radiology. 2015; 275: 589-598
Procopet et al., 2015
). TE was less applicable, and both techniques had similar accuracy for the diagnosis of CSPH.In summary, in the available studies, the applicability and diagnostic accuracy of both techniques closely resemble those of TE (for CSPH p-SWE: AUROC 0.82–0.90; 2-D SWE: AUROC 0.80–0.92) (
Berzigotti, 2017
). Cutoffs are, however, not yet well defined and vary across studies (pSWE: 2.17–2.58 m/s; 2-D SWE: 15.2–24.5 kPa). Similar considerations apply to the diagnosis of varices.One study compared TE with p-SWE (
Salzl et al., 2014
), and two studies concomitantly evaluated TE and 2-D SWE (- Salzl P
- Reiberger T
- Ferlitsch M
- Payer BA
- Schwengerer B
- Trauner M
- Peck-Radosavljevic M
- Ferlitsch A
Evaluation of portal hypertension and varices by acoustic radiation force impulse imaging of the liver compared to transient elastography and AST to platelet ratio index.
Ultraschall Med. 2014; 35: 528-533
Elkrief et al., 2015
, - Elkrief L
- Rautou PE
- Ronot M
- Lambert S
- Dioguardi Burgio M
- Francoz C
- Plessier A
- Durand F
- Valla D
- Lebrec D
- Vilgrain V
- Castera L
Prospective comparison of spleen and liver stiffness by using shear-wave and transient elastography for detection of portal hypertension in cirrhosis.
Radiology. 2015; 275: 589-598
Procopet et al., 2015
), reporting similar accuracy for the detection of CSPH. Because of the limited evidence to date, non-invasive criteria to rule out varices based on p-SWE or 2-D SWE cannot yet be recommended.Spleen stiffness measurement (SSM) has been proposed as an additional parameter potentially better correlating with portal pressure, irrespective of its cause. Data in cirrhosis are conflicting. A meta-analysis of 16 studies (using either TE, p-SWE or 2-D SWE) pointed to the superiority of this method (
Ma et al., 2016
), but the applicability of TE and 2-D SWE in this setting (about 70%) and the heterogeneity of the populations assessed do not allow recommendations on its use in clinical practice. Recent studies using TE found that LS was more accurate than spleen stiffness (SS) for the diagnosis of CSPH (AUROCs of 0.95 vs. 0.85 [Zykus et al., 2015
]; 0.78 vs. 0.63 [Elkrief et al., 2015
]). Several studies suggested that SS measurement (SSM) using pSWE could better predict the presence of varices and high-risk varices compared with LS. For example, one study including 340 cirrhotic patients and 16 healthy volunteers with invasive endoscopy as the reference standard found that a shear wave velocity cutoff value of 3.30 m/s identified high-risk esophageal varices, with a negative predictive value, sensitivity and accuracy of 0.994, 0.989 and 0.721, respectively (- Elkrief L
- Rautou PE
- Ronot M
- Lambert S
- Dioguardi Burgio M
- Francoz C
- Plessier A
- Durand F
- Valla D
- Lebrec D
- Vilgrain V
- Castera L
Prospective comparison of spleen and liver stiffness by using shear-wave and transient elastography for detection of portal hypertension in cirrhosis.
Radiology. 2015; 275: 589-598
Takuma et al., 2013
). In another study, SSM cutoff values of 3.36 and 3.51 m/s identified patients with esophageal varices and high-risk esophageal varices, respectively, with negative predictive values of 96.6% and 97.4%, respectively (Dietrich et al., 2017a
). Several additional studies have found SSM to be predictive of esophageal varices (- Dietrich CF
- Bamber J
- Berzigotti A
- Bota S
- Cantisani V
- Castera L
- Cosgrove D
- Ferraioli G
- Friedrich-Rust M
- Gilja OH
- Goertz RS
- Karlas T
- de Knegt R
- de Ledinghen V
- Piscaglia F
- Procopet B
- Saftoiu A
- Sidhu PS
- Sporea I
- Thiele M
EFSUMB guidelines and recommendations on the clinical use of liver ultrasound elastography, update 2017 (long version).
Ultraschall Med. 2017; 38: e16-e47
Sigrist et al., 2017
). LSMs obtained with 2-D SWE are higher in patients with esophageal varices of any size and are further increased in patients with large varices. However, reliable cutoff values are not available yet. No strong recommendation regarding the cutoff values for 2-D SWE can be given, and further evidence is needed.Sequential LSMs and SSMs using 2-D SWE have been recently proposed to improve the selection of patients requiring endoscopy (
Jansen et al., 2016b
).- Jansen C
- Bogs C
- Verlinden W
- Thiele M
- Moller P
- Gortzen J
- Lehmann J
- Vanwolleghem T
- Vonghia L
- Praktiknjo M
- Chang J
- Krag A
- Strassburg CP
- Francque S
- Trebicka J
Shear-wave elastography of the liver and spleen identifies clinically significant portal hypertension: A prospective multicentre study.
Liver Int. 2016; 37: 396-405
RECOMMENDATION 9: SWE has high diagnostic accuracy for detecting cirrhosis, better at ruling out (high negative predictive value >90%) than ruling in. (LoE 1a, GoR A) (10,0,0)
Clinical decompensation and other clinical endpoints
Liver stiffness measurements obtained with TE are able to predict liver-related events (clinical complications, HCC and liver-related death) as confirmed in a meta-analysis (
Singh et al., 2013
). As for clinical decompensation, LSMs ≥21 kPa were as accurate as HVPG ≥10 mm Hg in one study (Robic et al., 2011
). LSM by 2-D SWE also predicted clinical decompensation in one study (Grgurevic et al., 2015
). For p-SWE, data on this aspect are still lacking.- Grgurevic I
- Bokun T
- Mustapic S
- Trkulja V
- Heinzl R
- Banic M
- Puljiz Z
- Luksic B
- Kujundzic M
Real-time two-dimensional shear wave ultrasound elastography of the liver is a reliable predictor of clinical outcomes and the presence of esophageal varices in patients with compensated liver cirrhosis.
Croat Med J. 2015; 56: 470-481
Spleen stiffness measurements predicted clinical decompensation in one study using TE (
Colecchia et al., 2014
) and one study using 2-D SWE (- Colecchia A
- Colli A
- Casazza G
- Mandolesi D
- Schiumerini R
- Reggiani LB
- Marasco G
- Taddia M
- Lisotti A
- Mazzella G
- Di Biase AR
- Golfieri R
- Pinzani M
- Festi D
Spleen stiffness measurement can predict clinical complications in compensated HCV-related cirrhosis: a prospective study.
J Hepatol. 2014; 60: 1158-1164
Grgurevic et al., 2015
). In one study using p-SWE, SSM predicted variceal bleeding (- Grgurevic I
- Bokun T
- Mustapic S
- Trkulja V
- Heinzl R
- Banic M
- Puljiz Z
- Luksic B
- Kujundzic M
Real-time two-dimensional shear wave ultrasound elastography of the liver is a reliable predictor of clinical outcomes and the presence of esophageal varices in patients with compensated liver cirrhosis.
Croat Med J. 2015; 56: 470-481
Takuma et al., 2016a
a).Changes in LSMs do not correlate with changes in HVPG in patients undergoing therapy with non-selective beta blockers (
Reiberger et al., 2012
). Yearly LSM to follow up patients with portal hypertension has been suggested (de Franchis and Baveno, 2015
) but has not been validated yet.RECOMMENDATION 10: Liver stiffness measurements of TE >20 kPa can be used to identify patients likely bearing clinically significant portal hypertension (HVPG ≥10 mm Hg). (LoE 2b, GoR B) (10,0,0)
RECOMMENDATION 11: Liver stiffness measurement using TE<20–25 kPa combined with platelet count >110–150 × 106/mL is useful in ruling out varices needing treatment. (LoE 2b, GoR B) (10,0,0)
RECOMMENDATION 12: Liver stiffness measurement holds prognostic value in compensated cirrhosis, and the higher the value, the higher is the risk of clinical complications. (LoE 2b, GoR B) (10,0,0)
Pediatrics
Preliminary data on SWE techniques including TE, p-SWE and 2-D SWE have been published for the evaluation and follow-up of liver fibrosis in children (
Behairy Bel et al., 2016
, Belei et al., 2016
, Chen et al., 2016a
, Chen et al., 2016b
, Desai et al., 2016
, Ferraioli et al., 2017
, Franchi-Abella et al., 2016
, - Franchi-Abella S
- Corno L
- Gonzales E
- Antoni G
- Fabre M
- Ducot B
- Pariente D
- Gennisson JL
- Tanter M
- Correas JM
Feasibility and diagnostic accuracy of Supersonic shear-wave elastography for the assessment of liver stiffness and liver fibrosis in children: A pilot study of 96 patients.
Radiology. 2016; 278: 554-562
Garcovich et al., 2017
, Gersak et al., 2016
, Ghaffar et al., 2016
, Hanquinet et al., 2016
, Hattapoglu et al., 2016
, Jung et al., 2017
, Kamble et al., 2017
, Lodwick et al., 2017
, Mann et al., 2016
, Ozkan et al., 2017
, Phelps et al., 2017
, Raizner et al., 2017
, Tokuhara et al., 2016
, Trout et al., 2016
, Yoon et al., 2017
). Normal values in liver elasticity measured by SE in healthy infants and children were reported (Selmi et al., 2014
). In comparison to adult patients, different factors are encountered in children. The age, size and specific anatomy of the patients result in different probe diameters and eventually different examination techniques, including sedation, resulting in different cutoff values. This means that the cooperation of children (including breathholding) and cooperation of parents have to be taken into account. There is a variety of specific pediatric etiologies of diseases, with different influencing factors as well. In many diseases, the cutoff values are not as precisely known as they should be; therefore, individual follow-up examination plays a major role.Examination technique and normal values
The Fibroscan S probe (tip diameter of 5 mm compared with 7 mm for the M probe) has been adapted to the needs of children. TE is technically feasible and reliable in children of all age groups, but less successful in children <6 y old. Successful LSMs are even rarer in children <24 mo. The current recommendations from the manufacturer suggest using the S1 probe for thorax diameter <45 cm, S2 for 45–75 cm and M probe for thorax diameter >75 cm. The median and upper limit of normal values increase significantly with age (
Engelmann et al., 2012
, Lewindon et al., 2016
, Tokuhara et al., 2016
). The values were 4.4, 4.7 and 5.1 kPa in children 0–5, 6–11 and 12–18 y of age (p = 0.001), respectively, while the IQR decreased with age (0.8 0.7, and 0.6 kPa) (Engelmann et al., 2012
). In some studies, females exhibited lower median LSMs than males (4.7 vs. 5.6 kPa, p < 0.005) (Engelmann et al., 2012
), but no differences in other studies (Goldschmidt et al., 2013
, Lewindon et al., 2016
).Studies with a smaller number of patients, but with results similar to those obtained with TE data, have been obtained using p-SWE (
Bailey et al., 2017
, Trout et al., 2016
). In 132 children, the mean value of p-SWE measurements was 1.16 m/s (standard deviation: ±0.14 m/s) (Eiler et al., 2012
). Point SWE was feasible in children of any age (Hanquinet et al., 2013
, Matos et al., 2014
).It has been found that three acquisitions of a 2-D SWE technique can be enough for assessing SWSs in children >6 y, regardless of breathing status or hepatic pathology. More acquisitions are recommended for children <5 y, during free breathing (
Jung et al., 2017
, Shin et al., 2016
).Published evidence obtained with SE in children is scarce and contradictory (
Schenk et al., 2014a
, Schenk et al., 2014b
, Selmi et al., 2014
).Staging of fibrosis
The correlation of LSM with fibrosis stages has been examined in chronic liver diseases of different etiologies, with promising results (
Behairy Bel et al., 2016
). It must be taken into account that each liver disease may present different cutoff values when interpreting LSM for assessing fibrosis and may also depend on the severity of inflammation. General anesthesia and food intake also significantly increase liver stiffness in healthy children (de Ledinghen et al., 2007
, - de Ledinghen V
- Le Bail B
- Rebouissoux L
- Fournier C
- Foucher J
- Miette V
- Castera L
- Sandrin L
- Merrouche W
- Lavrand F
- Lamireau T
Liver stiffness measurement in children using FibroScan: Feasibility study and comparison with Fibrotest, aspartate transaminase to platelets ratio index, and liver biopsy.
J Pediatr Gastroenterol Nutr. 2007; 45: 443-450
Lee et al., 2013
, Raizner et al., 2017
). No general conclusions have been drawn so far to allow staging of fibrosis.Point SWE and 2-D SWE techniques may have advantages in differentiating different stages of fibrosis (
Fontanilla et al., 2014
, - Fontanilla T
- Canas T
- Macia A
- Alfageme M
- Gutierrez Junquera C
- Malalana A
- Luz Cilleruelo M
- Roman E
- Miralles M
Normal values of liver shear wave velocity in healthy children assessed by acoustic radiation force impulse imaging using a convex probe and a linear probe.
Ultrasound Med Biol. 2014; 40: 470-477
Marginean and Marginean, 2012
, Ozkan et al., 2017
, Pinto et al., 2014
, Tomita et al., 2013
). Liver diseases associated with cystic fibrosis have been examined using p-SWE (- Tomita H
- Hoshino K
- Fuchimoto Y
- Ebinuma H
- Ohkuma K
- Tanami Y
- Du W
- Masugi Y
- Shimojima N
- Fujino A
- Kano M
- Fujimura T
- Ishihama H
- Shimizu T
- Tanabe M
- Saito H
- Sakamoto M
- Hibi T
- Kitagawa Y
- Kuroda T
Acoustic radiation force impulse imaging for assessing graft fibrosis after pediatric living donor liver transplantation: A pilot study.
Liver Transplant. 2013; 19: 1202-1213
Canas et al., 2015
). With TE as a reference method, the sensitivity of p-SWE for detecting fibrosis F1 was 71.4%, for F2 77.8%, for F3 62.5% and for F4 71.4%. The sensitivity of 2-D SWE for detecting F1 was 92.8%, for F2 83.3%, for F3 87.5% and for F4 85.7%. Significant correlations were found between TE and 2-D SWE (κ correlation factor = 0.843, p = 0.001) (Belei et al., 2016
).Follow-up examinations
Pediatric diseases are rare; therefore, large studies presenting reliable data in a large cohort of patients are lacking. Follow-up examinations are recommended for pediatric patients with liver diseases to screen for complications including liver cirrhosis, portal hypertension and malignant transformation (
Yoon et al., 2017
). In patients with biliary atresia, the time for LSMs after the Kasai procedure for liver transplantation is important (Hanquinet et al., 2015
, Hanquinet et al., 2016
) and promising (Chen et al., 2016b
, Chongsrisawat et al., 2011
). Follow-up examinations are generally necessary after liver transplantation (Tomita et al., 2013
).- Tomita H
- Hoshino K
- Fuchimoto Y
- Ebinuma H
- Ohkuma K
- Tanami Y
- Du W
- Masugi Y
- Shimojima N
- Fujino A
- Kano M
- Fujimura T
- Ishihama H
- Shimizu T
- Tanabe M
- Saito H
- Sakamoto M
- Hibi T
- Kitagawa Y
- Kuroda T
Acoustic radiation force impulse imaging for assessing graft fibrosis after pediatric living donor liver transplantation: A pilot study.
Liver Transplant. 2013; 19: 1202-1213
The combination of TE with pediatric NAFLD fibrosis index has been examined in children with NAFLD to assess the grade of fibrosis (
Alkhouri et al., 2013
). No recommendation can be given so far. CAP (Sasso et al., 2010
) allows estimation of liver steatosis in pediatric (obese) patients (- Sasso M
- Beaugrand M
- de Ledinghen V
- Douvin C
- Marcellin P
- Poupon R
- Sandrin L
- Miette V
Controlled 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.
Ultrasound Med Biol. 2010; 36: 1825-1835
Desai et al., 2016
). No recommendation can be given so far.RECOMMENDATION 13: There is insufficient evidence to make a recommendation on the use of SWE for liver stiffness assessment in pediatric patients. (LoE 5, GoR D)(10,0,0)
Focal liver lesions
Diagnosis of focal liver lesions (FLLs) is needed to identify patients with malignant liver disease, to determine the correct management and to differentiate these patients from those with benign and insignificant pathology. For many years, contrast-enhanced computed tomography and MR scans, and more recently contrast-enhanced ultrasound (CEUS), have shown their value and ability to provide correct diagnoses without the requirement for surgery or biopsy. Currently, the use of elastography for characterization of FLLs remains investigational. It is hoped that elastography may supplement imaging to give more specific diagnoses in selected patients.
Although several reports document that malignant lesions are more likely stiffer than benign lesions, there is significant overlap. Both benign and malignant lesions can be soft or stiff compared with normal liver. In addition, the stiffness of the liver varies significantly with fibrosis. So, in any given patient elastography is not able to characterize liver lesions with significant accuracy for clinical use (
Omichi et al., 2015
, Yu and Wilson, 2011
). At present, sonoelastography is not recommended for characterization of FLLs (Barr et al., 2016b
). However, there are a few situations in which FLL stiffness may be of benefit, for example, focal nodular hyperplasia versus hepatic adenoma and in HCC cases (see Supplement 3, online only).RECOMMENDATION 14: There is insufficient evidence to make a recommendation on the use of SWE for differentiation between benign and malignant lesions and characterization of focal liver lesions. (LoE 5, GoR D) (10,0,0)
Assessment and grading of hepatic steatosis
Non-alcoholic fatty liver disease is becoming the leading cause of chronic liver disease worldwide. The term comprises a range of conditions, from simple steatosis to NASH. This latter may evolve into cirrhosis and its complications.
Even though liver biopsy is considered the gold standard for steatosis grading, the procedure cannot be used to screen a large population and is unsuitable for monitoring changes that may occur over short periods.
The CAP has been proposed for non-invasive grading liver steatosis (
Sasso et al., 2010
).- Sasso M
- Beaugrand M
- de Ledinghen V
- Douvin C
- Marcellin P
- Poupon R
- Sandrin L
- Miette V
Controlled 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.
Ultrasound Med Biol. 2010; 36: 1825-1835
Failure
In a prospective study of 5323 examinations performed in patients with chronic liver diseases with the M probe, the CAP failure rate (defined as no results) was 7.7% (
de Ledinghen et al., 2014
). The factors independently associated with CAP failure were female, overweight or obesity and metabolic syndrome, consistent with those already reported for liver stiffness (Castera et al., 2010
). In another recent study based on 1696 examinations, in 992 NAFLD patients, in whom both M and XL probes were used depending on the skin-to-liver capsule distance, the failure rate was lower: 3.2% (Vuppalanchi et al., 2018
).- Vuppalanchi R
- Siddiqui MS
- Van Natta ML
- Hallinan E
- Brandman D
- Kowdley K
- Neuschwander-Tetri BA
- Loomba R
- Dasarathy S
- Abdelmalek M
- Doo E
- Tonascia JA
- Kleiner DE
- Sanyal AJ
- Chalasani N
for the NASH Clinical Research Network
Performance characteristics of vibration-controlled transient elastography for evaluation of non-alcoholic fatty liver disease.
Performance characteristics of vibration-controlled transient elastography for evaluation of non-alcoholic fatty liver disease.
Hepatology. 2018; 67: 134-144
Reproducibility
Reproducibility has been assessed in two independent studies using the M probe (
Ferraioli et al., 2014b
, Recio et al., 2013
). The concordance between observers was excellent, 0.82 (95% CI: 0.78–0.85) (- Recio E
- Cifuentes C
- Macias J
- Mira JA
- Parra-Sanchez M
- Rivero-Juarez A
- Almeida C
- Pineda JA
- Neukam K
Interobserver concordance in controlled attenuation parameter measurement, a novel tool for the assessment of hepatic steatosis on the basis of transient elastography.
Eur J Gastroenterol Hepatol. 2013; 25: 905-911
Pineda et al., 2009
) and 0.84 (95% CI: 0.77–0.88) (- Pineda JA
- Recio E
- Camacho A
- Macias J
- Almodovar C
- Gonzalez-Serrano M
- Merino D
- Tellez F
- Rios MJ
- Rivero A
Grupo Andaluz de Hepatitis Virica de la Sociedad Andaluza de Enfermedades I
Liver stiffness as a predictor of esophageal varices requiring therapy in HIV/hepatitis C virus-coinfected patients with cirrhosis.
Liver stiffness as a predictor of esophageal varices requiring therapy in HIV/hepatitis C virus-coinfected patients with cirrhosis.
J Acquired Immune Defic Syndr. 2009; 51: 445-449
Recio et al., 2013
), respectively. However, the agreement between raters decreased for body mass index (BMI) >30 kg/m2 (0.65) and for CAP values <240 dB/m (0.44) (- Recio E
- Cifuentes C
- Macias J
- Mira JA
- Parra-Sanchez M
- Rivero-Juarez A
- Almeida C
- Pineda JA
- Neukam K
Interobserver concordance in controlled attenuation parameter measurement, a novel tool for the assessment of hepatic steatosis on the basis of transient elastography.
Eur J Gastroenterol Hepatol. 2013; 25: 905-911
Ferraioli et al., 2014b
).A recent study of 838 NAFLD patients (BMI: 33.6 ± 6.5 kg/m2), in whom both the M and XL probes were used, found that the intra-observer and inter-observer correlations were high overall: r = 0.82 and r = 0.70, respectively. However, the correlation decreased with the XL probe (M probe vs. the XL probe: intra-observer correlation: r = 0.85 vs. 0.75, p = 0.0003; inter-observer correlation r = 0.64 vs. 0.68, p = 0.71) (
Vuppalanchi et al., 2018
- Vuppalanchi R
- Siddiqui MS
- Van Natta ML
- Hallinan E
- Brandman D
- Kowdley K
- Neuschwander-Tetri BA
- Loomba R
- Dasarathy S
- Abdelm