Clinical Radiology xxx (xxxx) xxx

Contents lists available at ScienceDirect

Clinical Radiology
journal homepage: www.clinicalradiologyonline.net

Review

Ultrasound-based liver elastography in the

assessment of fibrosis
C. Fang 1, *, A. Lim 2, P.S. Sidhu 1
1
Department of Radiology, King’s College Hospital NHS Foundation Trust, London, UK
2
Department of Radiology, Imperial College Healthcare NHS Trust, London, UK

Ultrasound-based elastography has rapidly replaced the need for liver biopsy in most patients
with chronic liver disease in recent years. The technique is now widely supported by many
manufacturers. This review will introduce various current ultrasound-based elastography
techniques, review the physics and scanning techniques, discuss potential cofounding factors
as well as summarising the evidence for its use in staging liver fibrosis using shear-wave
elastography among different disease aetiologies. Future challenges and directions will be
also be discussed.
Ó 2020 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

Introduction Liver biopsy has traditionally been used as the reference

Liver fibrosis is the common endpoint of many chronic
liver diseases. Assessing the severity of liver fibrosis plays
an important role in disease management. Significant se-
vere fibrosis or cirrhosis represents two clinically important
endpoints in patients with viral hepatitis. Significant
fibrosis is an indication for starting anti-viral treatment
whilst severe fibrosis or cirrhosis warrants closer moni-
toring of complications such as portal hypertension and the
development of malignancy, with hepatocellular carcinoma
particularly relevant. For patients with other causes of
chronic liver disease, detection of cirrhosis is also the most
relevant clinical endpoint.1 The stage of liver fibrosis is used
to evaluate the severity of liver disease, guiding treatment
strategy. Assessing the regression of the fibrosis is used as a
surrogate goal for assessing the efficacy of drug therapy in
viral hepatitis.
standard in diagnosing and grading liver fibrosis. There are a
number of histological assessments of liver fibrosis grading
classifications. Of those, the METAVIR2 and Ishak3 scores are
the most widely used in assessing liver fibrosis in patients
with chronic hepatitis. They divide fibrosis grade into F0e4
(METAVIR scores) and F0e6 stages (Ishak score) with F0
being normal and stage 4 or 6 representing cirrhosis. Where
fibrosis scores are discussed in this review, the METAVIR
score is used. Liver biopsy is an invasive procedure associ-
ated with patient discomfort and occasionally with serious
complications.4,5 Many patients with chronic liver disease
require a number of liver biopsies to monitor disease pro-
gression over time and are often unwilling to undergo
repeated liver biopsies. In addition, the accuracy of liver
biopsy is limited, both by a recognised sampling error given
that <1/50,000 of the liver is assessed and poor intra- and
inter-observer variability on histological interpretation.6,7

* Guarantor and correspondent: C. Fang, Department of Radiology, King’s College Hospital, Denmark Hill, London, SE5 9RS, UK. Tel.: þ44 203 299 4164.
E-mail address: chengfang@nhs.net (C. Fang).

https://doi.org/10.1016/j.crad.2020.01.005
0009-9260/Ó 2020 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

Please cite this article as: Fang C et al., Ultrasound-based liver elastography in the assessment of fibrosis, Clinical Radiology, https://doi.org/
10.1016/j.crad.2020.01.005
2 C. Fang et al. / Clinical Radiology xxx (xxxx) xxx

An ultrasound-based assessment of liver stiffness, of the shear wave increases. Therefore, SWE can be used as a
termed elastography, has been developed over the last 10 quantitative means of measuring the degree of liver fibrosis.
years to assess fibrosis with the assumption that liver There are increasingly more manufacturers introducing this
stiffness increases with increasing levels of fibrosis, with new technology, with machines allowing measurement of
cirrhosis the most “stiff” elastography finding. There are a shear-wave velocity using both pSWE and 2D-SWE (Table 1).
number of ultrasound-based elastography methods avail- The tissue stiffness expressed in shear-wave velocity in
able for assessing liver stiffness. Strain elastography (SE) is metres per second is the preferred unit. This is because re-
an elastography technique that is reliant on manual sults expressed in kilopascals require conversion from the
compression to generate tissue distortion. The difference in velocity measurement and several pre-requisite assump-
the degree of distortion upon external compression is used tions for such conversion are often not met.12
as a qualitative means to assess the tissue elasticity and is
not used often in the assessment of liver fibrosis, being
Scanning technique
generally reserved for more superficial structures. Shear-
wave elastography (SWE) is the technique that is more
Patient should fast for at least a minimum of 2 hours
commonly applied to the assessment of liver fibrosis and
prior to the examination, and to rest for 10 minutes prior to
has a substantial advantage over liver biopsy of being non-
the elastography study.12 Food ingestion within 2e3
invasive and painless, with likely higher patient compliance
hours13,14 and exercise both increase liver stiffness mea-
than a biopsy and without the need for the associated
surements and can lead to overestimating the stage of
medical costs that surround the liver biopsy procedure. The
fibrosis stiffness.15 The measurements are obtained from
National Institute for Health and Care Excellence (NICE)
the right lobe of the liver, via an intercostal space, in brief
recommended adopting a particular elastography tech-
suspension of breathing with the right arm extended above
nique, point SWE (pSWE), termed Virtual Touch Quantifi-
the head. The measurements may be taken from the same
cation (VTQ, Siemens Healthineers) for diagnosing and
area of the liver repeatedly.
monitoring liver fibrosis in people with chronic hepatitis B
or C. According to the NICE guidelines, using pSWE to assess
TE
fibrosis saves £599.08 per patient compared to a liver bi-
opsy.8 In this review, different ultrasound-based elastog-
TE is commonly known by its brand name as FibroScan.
raphy techniques are described, inclusive of the
The operator should align the transducer vertically against
performance methodology, and their clinical role in staging
the skin at the intercostal space over the presumed (as there
liver fibrosis and detection of liver related complications.
is no visualisation of structures) right lobe of the liver,
adjust the pressure applied to the skin according to the
pressure indicator on the screen and push the button to
Physics of SWE
generate a mechanical pulse during brief a breath suspen-
sion period.16 Shear-wave velocity is normally displayed as
Transient elastography (TE; FibroScan, Echosens, Paris,
kilopascals (Fig 1). According to the manufacturer’s
France), pSWE, and two-dimensional (2D) multidimensional
SWE (2D-SWE) are the three techniques that comprise SWE.
TE is well established. The machine does not incorporate an Table 1
ultrasound imaging facility and measurements are obtained Examples of currently available commercial systems (applications).

in a blinded fashion over the anatomical position of the liver. Commercially available systems Elastography techniques
SWE techniques measure the propagation speed of a shear FibroScan, (Echosens, Paris, France) Transient elastography
wave transmitted from the transducer through the liver. TE Acuson e Virtual Touch Quantification Point shear-wave
uses a mechanically induced impulse at the skin surface9 (VTQ; Siemens, Mountain View, CA elastography
USA)
while pSWE and some 2D-SWE methods use a higher-
EPIQ7 e ElastPQ technique (Philips Point shear-wave
energy ultrasound-induced focused radiation force im- Medical System, Bothell, WA, USA) elastography
pulse (also termed acoustic radiation force impulse [ARFI]) Ascendus e Hi-VISION (Hitachi Ltd, Point shear-wave
at depth to distort the tissue and thus generate shear Japan) elastography
waves.10 The difference between pSWE and 2D-SWE is that MyLab Twice (Esaote SpA, Genoa, Italy) Point shear-wave
elastography
the former emits a single shear wave at a single frequency
RS80 e S-Shearwave (Samsung Point shear-wave
for each measurement while the latter emits multiple pulse Medison, Seoul, South Korea) elastography
waves using a wide frequency range. The shear wave is a Aixplorer (Supersonic imagine, Aix-en- 2D shear-wave elastography
type of low-frequency mechanical wave, which travels Provence, France)
LOGIQE9 e 2D comb-push (GE 2D shear-wave elastography
perpendicular to the medium of displacement at a low ve-
Healthcare, Chalfont, UK)
locity (1e10 m/s). The speed of shear waves can be used RS85 - S-Shearwave (Samsung Medison, 2D shear-wave elastography
to determine the elasticity of the tissue using the equation, Seoul, South Korea)
E ¼ 3rc2, where E is Young’s Modulus liver elasticity, Aplio 500 e Acoustic Structure 2D shear-wave elastography
C is shear-wave velocity, and r is the density of the tissue Quantification (ASQ; Japan)
EPIQ7 e ElastPQ imaging (Philips 2D shear-wave elastography
(kg/m3).11 In practical terms, as liver fibrosis progresses, the
Medical System, Bothell, WA, USA)
liver becomes stiffer and as a result, the propagation speed

Please cite this article as: Fang C et al., Ultrasound-based liver elastography in the assessment of fibrosis, Clinical Radiology, https://doi.org/
10.1016/j.crad.2020.01.005
 C. Fang et al. / Clinical Radiology xxx (xxxx) xxx
Figure 1 Screen display of a TE study (Echosens, Paris, France). Liver
stiffness is displaced in kilopascals (open arrow). The quality-control
parameter is displayed as IQR/M (white arrow). Notice the TE ma-
chine does not allow the operator to visualise the liver prior to taking
the measurement.
recommendation, a successful measurement rate of <60%
or the value of interquartile range over median (IQR/M) of
>0.3 indicates low-quality measurements,17 and should
therefore not be taken into consideration during clinical
decision-making. The technical difficulty of obtaining valid
measurements in obese patients can be overcome by using
the XL instead of the M transducer. TE cannot be used in
patients with abdominal ascites.
pSWE and 2D-SWE
Patients are scanned in the same position as for transient
elastography, but with pSWE and 2D-SWE the examination
is performed using a conventional ultrasound machine, with
visualisation of the liver. The operator should scan the liver
via an intercostal approach and optimise the B-mode image
of liver, avoiding rib shadows before placing a region of in-
terest (ROI) box in the right lobe of the liver (segments V,
VIII, or VII), 1e2 cm away from the liver capsule (in order to
avoid reverberation artefact, and subcapsular stiffer tissue),
also avoiding large blood vessels, biliary tracts, and the
gallbladder, with the transducers at 90 in relation to the
liver capsule.12 The study measurement is initiated by
pressing the manufacturer’s designated button to generate
the shear wave in the ROI area while asking the patient to
briefly breath hold in a neutral position (<5 seconds). For
2D-SWE, a colour map of tissue elastogram will be displayed
over the ROI box from which multiple circular analysis boxes
Please cite this article as: Fang C et al., Ultrasound-based liver elastography in the assessment of fibrosis, Clinical Radiology, https://doi.org/
10.1016/j.crad.2020.01.005
3
of at least 10 mm in diameter can be placed over the selected
area within the ROI, avoiding liver vessels, biliary duct, or
artefacts. The advantage of 2D-SWE is not only that the ROI
box is larger, but also, unlike pSWE where the evaluated area
of liver parenchyma cannot be modified, 2D-SWE allows the
operator to select an analysis box within the original ROI box
(Fig 2). In contrast to TE, the presence of ascites does not
preclude performing pSWE or 2D-SWE studies.
Minimum number of measurements
A median of 10 measurements has been recommended
for TE and pSWE by the manufacturers, with strong expert
consensus support from the European Federation of Soci-
eties for Ultrasound in Medicine and Biology (EFSUMB)
guidelines.12 For 2D-SWE, EFSUMB guidelines12 and Sporea
et al.18 have suggested that a minimum of three measure-
ments may be taken, but the literature documents from
three to 20 measurements.12,16,19,20 The majority of the
pSWE studies for staging liver fibrosis have used the rec-
ommended 10 valid measurements with a few studies
obtaining varying number of measurements of five,21
six,22,23 12,24 or 2025 measurements; however, recently
Fang et al. suggested that fewer measurements may be
acceptable when using pSWE in the assessment of liver
stiffness, comparing the diagnostic accuracy liver fibrosis
stages between six and 10 measurements using histological
grading as a reference standard.26
Intra- and interobserver reliability
TE, pSWE, and 2D-SWE have all demonstrated excellent
intra- and interobserver reproducibility for the assessment
of liver elastography in healthy volunteers and patients
with chronic liver disease using intraclass coefficients (ICC
0.90)27 among different commercially available systems
(FibroScan,28e30 VTQ [Siemens, CA, USA],31e35 ElastPQ
[Philips Medical System, Bothell, WA, USA],33,36 LOGIQE9
[GE Healthcare, UK]19,37). Although supersonic imaging (SSI,
Aix-en-Provence, France) demonstrated similar excellent
intra-observer reproducibility in assessing healthy volun-
teers38,39 and patients,23,40,41 the interobserver reproduc-
ibility was found to be lower when compared to VTQ
(Siemens, CA).42 In addition, higher reproducibility has
been found in expert operators compared to novice opera-
tors when obtaining measurements using 2D-SWE.38,39
EFSUMB guidelines recommend the pSWE and 2D-SWE
studies are performed by operators who have obtained level
1 (core) competence in ultrasound.10 There have been no
guidelines regarding the definition for experienced pSWE
operators. For 2D-SWE, proposed competence levels
require performing at least 300 abdominal ultrasound ex-
aminations and 50 supervised 2D-SWE examinations.10,38
Intersystem variability
A study commissioned by the Quantitative Imaging
Biomarker Alliance (QIBA) of the Radiological Society of
North America (RSNA) to quantify the differences in
4 C. Fang et al. / Clinical Radiology xxx (xxxx) xxx

Figure 2 Screen displays of (a) pSWE (Siemens, USA) and (b) 2D-SWE (GE, UK). The thick white arrows show the liver capsular and open white
arrows the ROI are perpendicular to the liver capsule (white arrows). In pSWE, the result is displayed on the left upper corner as an average
shear-wave velocity from ROI, while in 2D-SWE, the colour-coded map of shear-wave velocity is displayed in the ROI and a separate analysis
circle in the ROI can be drawn for calculating the shear-wave velocity.

shear-wave velocity obtained with different machines Normal values

(FibroScan, Echosens, Philips iU22, [Philips Medical],
ACUSON S2000 [Siemens], and Aixplorer [Supersonic
imagine, Aix-en-Provence]) on phantoms concluded that
there is a significant difference in shear-wave velocity
among different commercial systems and at different
depths.43 Using “soft” and “hard” phantoms to simulate
“normal” and “cirrhotic” livers, Dillman et al. found that
shear-wave velocity obtained in soft phantoms were
significantly different between those obtained by Acuson
S3000 and Aixplorer (p¼0.003).44 Shin et al. also
demonstrated that there is a significant difference of
mean shear-wave velocity measured on the three ultra-
sound elastography machines (p0.002) and the mea-
surements were significantly affected by the acquisition
depths and transducers.45 Recently, evaluation of inter-
system variability of the shear-wave velocity has been
studied on healthy volunteers and patients using seven
commercially available machines (Acuson S2000, EPIQ7,
Hi-Vision Ascendus, MyLab Twice, Aixplorer, Aplio 500,
FibroScan). Although the study showed excellent agree-
ment between shear-wave velocities obtained with
different machines, the mean difference of shear-wave
velocity between pSWE and 2D-SWE were as high as
3.64 kPa, and was sufficient to assign patients to a
different stage of fibrosis.27 In addition, the differences in
shear-wave velocity measurement obtained from different
machines display proportional bias rather than systematic
bias meaning the measurements are not always higher or
lower, but that the difference varies depending on liver
stiffness.37 For example, pSWE system tends to give lower
values than FibroScan in the higher range of liver stiff-
ness27 while the measured value tends to be higher from
2D-SWE compared to FibroScan in softer livers.43 There-
fore, liver stiffness measurements obtained from different
machines are not interchangeable and a different cut-off
value for staging liver fibrosis should be used for
different machines.12,27 Follow-up studies of liver stiffness
should ideally be performed using the same machine.
Dong et al. summarised the current literature for liver
stiffness measurement in healthy volunteers.46 Studies
including over 100 normal volunteers are existing for
TE,47e53 VTQ,54e58 ElastPQ,59,60 and SSI.23,61e64 Among
these larger studies, the mean/median liver stiffness mea-
surement using TE range between 4.1 kPa to 5.5 kPa with
the reported maximum liver stiffness measurement as high
as 17.5 kPa and calculated highest upper 95% percentile of
8.7 kPa assuming the data are normally distributed.47e53
The mean or median pSWE measurements using VTQ
and ElastPQ are between 1.03 to 1.19 m/s (maximum value:
1.71 m/s, and highest calculated 95% percentile value of
1.69 m/s). 2D-SWE measurements using Aixplorer has a
mean or median value between 4.95 to 5.5 kPa (maximum
value 8.7 kPa, 95% percentile value of 8.04 kPa). Significantly
higher liver stiffness measurements have been reported in
healthy men than in women using FibroScan,53 ElastPQ,
and SSI, but not with VTQ. Therefore, high liver stiffness
value may be seen in normal healthy volunteers, but a
normal liver stiffness value can exclude significant fibrosis.
Although the liver stiffness value in healthy volunteers
among different commercial systems should not differ
significantly from each other their values are not yet
established in larger studies.
Reliability indicator
Both EFSUMB and Society of Radiologists in Ultrasound
(SRU) recommend the use of IQR/M to assess data qual-
ity.12,65 IQR/M measures data variability and studies have
shown increased accuracy for classifying fibrosis staging
when only the measurements with high reliability (IQR/M
30%) are used.66e68 Ferraioli et al. also showed that an
increase in agreement between measurements taken from
different elastography machine when using measurements
with IQR/M 30%.27 Fang et al. showed a 2.2-fold and 4.9-

Please cite this article as: Fang C et al., Ultrasound-based liver elastography in the assessment of fibrosis, Clinical Radiology, https://doi.org/
10.1016/j.crad.2020.01.005
 C. Fang et al. / Clinical Radiology xxx (xxxx) xxx
fold increase in discordance with significant and severe
fibrosis histology with lower reliability (IQR/M 30%)
compared to high reliability (IQR/M >30%); however, there
are challenges in applying IQR/M as a quality measure.
Firstly, it can only be calculated retrospectively once the
measurements have been obtained. Secondly, a study has
shown the presence of significant fibrosis itself to be a
predictor for measurement with lower reliability.26 Newer
systems such as Hi-VISON (Hitachi, Tokyo, Japan)69,70 and S-
Shearwave (Samsung Medison, Seoul, South Korea)71 have
incorporated a reliability indicator, displayed at the time of
measurement, potentially allowing a reduction in the pro-
portion of low-reliability measurements taken. The above
quality criteria are not applicable to 2D-SWE, which
simultaneously evaluates the velocity of multiple shear
waves over a wide frequency band range. There are quality
indicators recommended by the 2D-SWE manufacturers.
For example, 2D propagation map (Fig 3) developed by
CannoneToshiba will provide user a visual aid of mea-
surement reliability during liver elastography measure-
ments with the smooth parallel lines on the map indicating
reliable measurements.72
Staging of liver fibrosis
Viral hepatitis
The primary role of elastography in chronic liver disease
is to determine the stage of liver fibrosis. The European
Association for the Study of the Liver (EASL-ALEH) clinical
guidelines recommend TE as part of non-invasive tests for
the evaluation of liver disease severity and prognosis;
however, it is advocated that liver stiffness measurement
should be interpreted by specialists in liver disease in
conjunction with patient’s clinical information and other
investigations (biochemical, radiological tests),73 and not
Figure 3 A 2D-SWE study (Canon Japan). Propagation map in the right screen where the more parallel the lines are, the more reliable the shear-
wave propagation and where a ROI should be placed. Note the distorted shear waves close to a vessel and liver capsule indicating that this would
not be a reliable place to take a speed/elasticity measurement.
Please cite this article as: Fang C et al., Ultrasound-based liver elastography in the assessment of fibrosis, Clinical Radiology, https://doi.org/
10.1016/j.crad.2020.01.005
5
used as a screening test in the general population.12 In large
studies evaluating the role of TE as a screening tool in the
general population (>45 years old), higher liver stiffness
measurements using TE have been found to be associated
with diabetes mellitus, obesity, and smoking, although the
cause of elevated liver stiffness is unknown.74,75 Early
studies have calculated the area under the receiver operator
characteristic curve (AUROC) to reflect the diagnostic per-
formance of elastography using liver biopsy as the reference
standard. The majority of the studies were using FibroScan,
VTQ, and SSI systems found that liver stiffness value
correlated strongly with fibrosis stages.76
TE has good diagnostic performance in staging liver
fibrosis in patients with hepatitis B. Three meta-analyses
examining the diagnostic performance of TE in patients
with hepatitis B virus (HBV) reported mean AUROC of
0.8225,77 0.859,78 0.8879 for predicting significant fibrosis
(F2) and mean AUROC of 0.9108,77 0.929,78 0.9379 for
predicting cirrhosis (F4). The cut-off values reported from
meta-analyses for F2 and F¼4 are 7.2e7.9 kPa and
11.7e12.2 kPa respectively.78,79 However, substantial over-
lap in liver stiffness values are observed among lower
fibrosis stages.77e81 In addition, these meta-analyses have
also confirmed that TE is better at predicting cirrhosis
(higher AUROCs) than significant fibrosis. Serum amino-
transferases level should be considered when interpreting
liver stiffness value as elevated liver stiffness has been re-
ported in patients with raised alanine aminotransferase
(ALT), which can lead to false-positive results in patient
with hepatitis B inflammatory flare.82 On the other hand, TE
of <5e6 kPa rules out significant fibrosis (and the need for
liver biopsy) in “inactive carriers” who have negative HBeAg
and normal ALT.73,83 Similar diagnostic performances have
been reported for hepatitis C virus (HCV)84,85 with reported
cut-off values of 5.2e9.5 kPa for significant fibrosis and
11.9e14.8 kPa for cirrhosis.73
6 C. Fang et al. / Clinical Radiology xxx (xxxx) xxx
Results from a meta-analysis comprising 13 studies
suggested that VTQ has similar diagnostic performance to
TE.86 NICE recommend the use of VTQ in the assessment
liver fibrosis in patients with HCV and HBV and also suggest
VTQ is as accurate as TE in assessing the degree of fibrosis.87
The AUROCs for significant fibrosis are 0.85e0.89 (1.21e1.34
m/s); for cirrhosis are 0.89e0.93 (1.55e2 m/s) in patients
with HCV.88,89 In patients with HBV, the AUROC (cut-offs)
for significant fibrosis and cirrhosis are 0.88 (1.35 m/s) and
0.93 (1.87 m/s).90 Like TE, the AUROCs are higher for iden-
tifying cirrhosis than significant fibrosis with reported
mean AUROCs of 0.88 and 0.91, respectively, from meta-
analysis91 using VTQ. Interestingly, the meta-analysis also
reported that the liver stiffness value measured with VTQ
are higher in patients with HCV than HBV.91
There are fewer 2D-SWE studies using the Axiplorer
system, which have demonstrated good diagnostic perfor-
mance for predicting significant fibrosis and cirrhosis.20 The
proposed cut-offs from a meta-analysis (based on 13 studies
and a total of 1,134 patients using Axiplorer) are 7.1 kPa
(HCV, HBV, non-alcoholic fatty liver disease [NAFLD]) for
F2 and 13 kPa (HCV, NAFLD), 11.5 kPa (HBV) for F4 with
limited reliability for NAFLD due to low patient numbers.76
The meta-analysis also showed that 2D-SWE is significantly
better than TE (through higher AUROCs) in predicting sig-
nificant fibrosis (p¼0.001) and cirrhosis (p¼0.022) for all
aetiologies.76 The gain in AUROC is biggest in patients with
HBV and smallest in patients with HCV.76 There are very
limited studies comparing the diagnostic performance of
staging fibrosis between pSWE and 2D-SWE. Cassinotto
et al. showed that 2D-SWE performed better than VTQ in
predicting significant fibrosis (F2).16
Studies have shown that both pSWE and 2D-SWE have a
higher success rate than TE.92,93 In addition, there are a few
other advantages of pSWE and 2D-SWE over TE including
the ability to assess the morphology of the liver and pres-
ence of liver related complications, visualise the ROI being
assessed, avoid vascular/biliary structures, and optimise the
depth of assessment. All of these have been found to affect
the diagnostic performance and interobserver reliability.
With the new generation of antiviral therapy, there are
increasing numbers of patients with a sustained virological
response. Histology regression of fibrosis/cirrhosis has been
shown94; however, the role of liver stiffness measurements
in assessing reversal of fibrosis are yet to be established. The
conventional cut-off value for different fibrosis stages may
not be applicable following viral eradication as the reduc-
tion of liver stiffness value may be as a result of reduction of
inflammation rather than regression of fibrosis.95
NAFLD
The screening for liver fibrosis in NAFLD patients is rec-
ommended by the EASL-ALEH clinical guidelines.73
Assessing liver fibrosis in patients with NAFLD can be
problematic due to increased body mass index, resulting in
an increased measurement acquisition failure rate. Never-
theless, TE shows high diagnostic sensitivity and specificity
in identifying F3 fibrosis. Systematic reviews of TE
Please cite this article as: Fang C et al., Ultrasound-based liver elastography in the assessment of fibrosis, Clinical Radiology, https://doi.org/
10.1016/j.crad.2020.01.005
involving 1,047 patients with NAFLD showed diagnostic
sensitivity of 85% and specificity of 82% in determining F3
fibrosis. Even higher levels of diagnostic accuracy was
achieved for identifying F4 fibrosis/cirrhosis (92% sensitivity
and 92% specificity).96 pSWE (VTQ) has also been shown to
have a similar level of sensitivity (80.2%) and specificity
(85.2%) in identifying significant fibrosis (F2) in patients
with NAFLD.97 A recent meta-analysis showed that both TE
and pSWE have excellent diagnostic accuracies in staging
advanced fibrosis and cirrhosis with AUCs reaching 0.94 in
patients with NAFLD.93 To date, there have been limited
studies investigating the diagnostic performance of 2D-
SWE in NAFLD patients. A pilot study comparing the diag-
nostic performance of pSWE (VTQ) and 2D-SWE (SSI)
showed that 2D-SWE has superior diagnostic accuracy in
identifying significant fibrosis while similar diagnostic ac-
curacy was achieved for severe fibrosis/cirrhosis.41
Alcoholic liver disease
TE can be used to exclude severe fibrosis or cirrhosis in
patients with alcoholic liver disease (ALD); however,
measuring liver stiffness in ALD patients with abnormal
liver function biochemical parameters may lead to false-
positive results as the measurement of liver stiffness can
be falsely elevated by increased transaminases, bilirubin, or
gamma-glutamyl transferase. Therefore, recommended
cut-off values in ALD are yet to be established with the risk
of overestimation of liver stiffness measurement in this
population. There is limited evidence available in terms of
the diagnostic accuracy using pSWE and 2D-SWE.
Other aetiologies
There are few studies investigating the accuracy of
staging liver fibrosis in patients with autoimmune liver
disease, but these studies have reported good diagnostic
accuracy using TE98e100 and 2D-SWE.101 In a cohort of 90
patients with autoimmune liver disease, Park et al. reported
diagnostic accuracy assessing fibrosis stage using ElastPQ is
better than the established serological markers (APRI and
FIB-4) using liver biopsy as the reference.100
Assessment of portal hypertension
Portal hypertension is a common and clinically impor-
tant complication of chronic liver disease. Patients with
significant portal hypertension are at increased risk of
developing varices and patients with severe portal hyper-
tension are at higher risk of acute variceal bleeding. The
severity of portal hypertension can be measured through
hepatic venous pressure gradient (HVPG) in an invasive
angiographic technique. HVPG of 10 or 12 mmHg sig-
nifies clinically significant or severe portal hypertension,
respectively.102 The presence and grading of oesophageal
varices is assessed invasively through upper gastrointes-
tinal endoscopy.
A number of clinical studies have evaluated the diag-
nostic performance of using liver or spleen stiffness
 C. Fang et al. / Clinical Radiology xxx (xxxx) xxx
ultrasound elastography as a non-invasive alternative. Evi-
dence from meta-analysis suggests that liver stiffness
measurement from TE is excellent (AUROC of 0.93) in pre-
dicting clinically significant portal hypertension (HVPG 10
mmHg) in patients with chronic liver disease.103 A more
recent meta-analysis showed good diagnostic performance
of clinically significant portal hypertension using liver
stiffness measurement and the diagnostic performance of
TE and pSWE/2D-SWE were also useful.104
Predicting and grading oesophageal varices based on
liver stiffness measurement is less satisfactory than pre-
dicting clinically significant portal hypertension with low
specificity (43e78%) despite high sensitivity (76e95%).
Spleen stiffness measurement has been proposed as a non-
invasive alternative to determine the presence and severity
of oesophageal varices. A study of using pSWE showed that
the negative predictive value and sensitivity of 0.994 and
0.989, respectively, in predicting high-risk oesophageal
varices using endoscopy as the reference standard.
Overall, the existing evidence suggests that liver or
spleen stiffness values have good correlation with HVPG up
to 12 mmHg and may be used as an initial assessment for
clinically significant portal hypertension, but currently, they
cannot replace invasive assessment as there is a lack of
evidence that these are accurate markers for severe portal
hypertension where the progression of portal hypertension
is less dependent on intrahepatic resistance due to
fibrosis.73
The vast majority of the studies published using
ultrasound-based elastography have used VTQ (PSW) and
SSI (2D-SWE).105 In the last 3 years, many vendors have
incorporated pSWE and 2D-SWE to allow both measure-
ments to be used simultaneously. Early results have shown
comparable diagnostic accuracy.72,106 In time, meta-analysis
from using these platforms will establish a body of evidence
for their clinical use.
The future challenges
Several confounding factors have been reported to
significantly elevate liver stiffness measurements using TE
and VTQ including elevated aminotransferases, congestive
heart failure, and extrahepatic cholestasis. Although stea-
tosis can attenuate the shear wave, the effect of steatosis on
shear-wave velocity is yet to be established and this will be
important in assessing patients with steatohepatitis. In
addition, factors associated with the performance accuracy
of newer pSWE and 2D-SWE systems are yet to be reported
and validated in larger studies.
The majority of the studies using pSWE and 2D-SWE
have been performed either with cohorts of mixed aetiol-
ogies of chronic liver disease or cohorts solely with viral
hepatitis. The diagnostic performance of elastography is yet
to be validated in other aetiologies of chronic liver disease
including ALD and NAFLD. It has becoming increasing clear
that the cut-off values for stages of fibrosis are likely to be
different based on the underlying aetiology. In addition, the
cut-off values reported in the literature are based on You-
den’s index, which maximise the combined sensitivity and
Please cite this article as: Fang C et al., Ultrasound-based liver elastography in the assessment of fibrosis, Clinical Radiology, https://doi.org/
10.1016/j.crad.2020.01.005
7
specificity. Therefore, the cut-offs vary among studies. In
clinical practice, one might also want to vary the emphasis
on sensitivity or specificity based on clinical needs. In
addition, the difference in cut-off value reported in litera-
ture may also be influenced by the difference in disease
prevalence in the study population. Therefore, cut-off value
selection should take into consideration the target pop-
ulation’s pre-test probability of cirrhosis.
Recent reviews suggest that TE has superior diagnostic
performance in predicting cirrhosis in HBV and NAFLD
compared to serum markers (APRI and FIB-4)107; however,
studies of the diagnostic accuracy of staging fibrosis by
combining serum markers and liver stiffness measurements
have yielded conflicting results with studies suggesting
both superior diagnostic accuracy in predicting significant
and cirrhosis108,109 and no significant improvement.110 The
usefulness of liver elastography as a tool for monitoring
treatment response is yet to be established.
Liver fibrosis may affect livers in a non-uniform manner.
The majority of clinical studies were performed in the deep
lobe of the right liver due to higher inter and intra-observer
reliability. Elastography as a non-invasive imaging tech-
nique may be used in assessing the different areas of liver.
The existing guidelines recommend taking repeated mea-
surements from one location; however, there are yet to be
any studies investigating the impact of taking stiffness
measurements from different lobes to compare their rela-
tive diagnostic accuracy.
Conclusion
In summary, ultrasound-based elastography is a cost-
effective and non-invasive method of assessing liver
fibrosis. Currently, it is better at predicting cirrhosis than
significant fibrosis and has a high negative predictive value.
It should be incorporated into the decision-making process
in managing patients with chronic liver disease. Further
large prospective studies are needed to cross validate newer
pSWE and 2D-SWE with TE/liver biopsy and to understand
some of the confounding factors affecting the liver stiffness.
This would allow the establishment of more robust cut-offs
for individual aetiologies and fibrosis stages.
Conflict of interest
The authors declare no conflict of interest.
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