Page 6 - NON-INVASIVE TESTS FOR EVALUATION OF LIVER DISEASE SEVERITY AND PROGNOSIS
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with failure and unreliable results rates of 2.7% and 11.6%, JOURNAL OF HEPATOLOGY
respectively [59].
based on two physical principles: strain displacement/imaging
An important question in clinical practice is whether unreli- and shear wave imaging and quantification [88]. The latter allows
able results translate into decreased accuracy. It has been sug- a better estimation of liver tissue elasticity/stiffness, and includes
gested that among the recommendations, the IQR/M <30% is point shear wave elastography (pSWE), also known as acoustic
the most important parameter for good diagnostic accuracy radiation force impulse imaging (ARFI) (Virtual touch tissue
[60,61]. In a recent study [62] in 1165 patients with chronic quantification™, Siemens; elastography point quantification,
liver diseases (798 with chronic hepatitis C) taking liver biopsy ElastPQ™, Philips) and 2D-shear wave elastography (2D-SWE)
as reference, TE reliability was related to two variables in (Aixplorer™ Supersonic Imagine, France). pSWE/ARFI involves
multivariate analysis: the IQR/M and LS measure. Indeed, the
presence of an IQR/M >30% and LS measure median P7.1 kPa mechanical excitation of tissue using short-duration ($262 lsec)
resulted in a lower accuracy (as determined by AUROC) than
that of the whole study population and these cases were there- acoustic pulses that propagate shear waves and generate
fore considered ‘‘poorly reliable’’. Conversely, the highest accu-
racy was observed in the group with an IQR/M 610% localized, l-scale displacements in tissue [89]. The shear wave
regardless of the LS measure. Also a recent study reported a sig-
nificant discrepancy in up to 20% of cases in patients without velocity (expressed in m/sec) is measured in a smaller region
cirrhosis between different FibroScan devices (402 vs. 502) than in TE (10 mm long and 6 mm wide), but the exact location
[63]. These results require further validation before any recom- where measurements are obtained can be selected by the opera-
mendation can be made. tor under B-mode visualization. A major advantage of pSWE/ARFI
is that it can be easily implemented on modified commercial
In order to minimize the number of patients with unreli- ultrasound machines (Acuson 2000/3000 Virtual Touch™
able results due to obesity, a new probe (XL, 2.5 MHz trans- Tissue Quantification, Siemens Healthcare, Erlangen, Germany;
ducer), allowing measurement of LS between 35 to 75 mm ElastPQ, iU22xMATRIX, Philips, Amsterdam, The Netherlands).
depth, has been developed [64–68]. Myers et al. [66] showed Its failure rate is significantly lower than that of TE (2.9% vs.
that in 276 patients with chronic liver disease (42% viral hep- 6.4%, p <0.001), especially in patients with ascites or obesity
atitis, 46% NAFLD) and a BMI >28 kg/m2, measurement failures [90]. Also its reproducibility is good, with ICC ranging from 0.84
were significantly less frequent with the XL probe than with to 0.87 [91–93]. However, like TE, pSWE/ARFI results are influ-
the M probe (1.1% vs. 16%; p <0.00005). However, unreliable enced by food intake [94] as well as necro-inflammatory activity
results were still observed with the XL probe in 25% of case and the serum levels of aminotransferases [95], both of which
instead of 50% with the M probe (p <0.00005). Also it is lead to an overestimation of liver fibrosis and have to be taken
important to note that stiffness values obtained with XL probe into account when interpreting the results. LS values obtained
are lower than that obtained with the M probe (by a median with pSWE/ARFI, in contrast to TE values, have a narrow range
of 1.4 kPa). (0.5–4.4 m/sec). This limits the definitions of cut-off values for
discriminating certain fibrosis stages and thus for making
Apart from obese patients, TE results can also be difficult to management decisions. Finally, quality criteria for correct inter-
obtain from patients with narrow intercostal space and are pretation of pSWE results remain to be defined.
nearly impossible to obtain from patients with ascites [49]. As
the liver is an organ with a distensible but non-elastic envelope 2D-SWE is based on the combination of a radiation force
(Glisson’s capsule), additional space-occupying tissue abnor- induced in tissues by focused ultrasonic beams and a very high
malities, such as edema, inflammation, extra-hepatic cholestasis, frame rate ultrasound imaging sequence capable of catching in real
or congestion, can interfere with measurements of LS, indepen- time the transient propagation of resulting shear waves [96]. The
dently of fibrosis. Indeed, the risk of overestimating LS values size of the region of interest can be chosen by the operator.
has been reported with other confounding factors including ala- 2D-SWE has also the advantage of being implemented on a com-
nine aminotransferase (ALT) flares [69–71], extra-hepatic mercially ultrasound machine (AixplorerÒ, Supersonic Imagine,
cholestasis [72], congestive heart failure [73], excessive alcohol Aix en Provence, France) with results expressed either in m/sec
intake [74–76], and food intake [77–80], suggesting that TE or in kPa at a wide range of values (2–150 kPa). Its failure rate is
should be performed in fasting patients (for at least 2 h) and significantly lower than that of TE [97–99], particularly in patients
results always interpreted being aware of these potential con- with ascites [98,99], but not in obese patients when the XL probe is
founding [81]. The influence of steatosis is still a matter of used for TE (10.4% vs. 2.6%, respectively) [100]. Similar to pSWE/
debate with conflicting results: some studies suggest that ARFI, quality criteria for 2D-SWE remain to be defined.
steatosis is associated to an increase in LS [82–84] whereas
others do not [85,86]. MR elastography uses a modified phase-contrast method to
image the propagation characteristics of the shear wave in the
Other liver elasticity-based imaging techniques liver [101]. Elasticity is quantified by MR elastography (expressed
Several other liver elasticity-based imaging techniques are being in kPa) using a formula that determines the shear modulus,
developed, including ultrasound-based techniques and 3-D mag- which is equivalent to one-third the Young’s modulus used with
netic resonance (MR) elastography [87]. Ultrasound elastography TE [102]. The theoretical advantages of MR elastography include
can be currently performed by different techniques, which are its ability to analyze almost the entire liver and its good
applicability in patients with obesity or ascites. However, MR
elastography remains currently too costly and time-consuming
to be used in routine practice and cannot be performed in livers
of patients with iron overload, because of signal-to-noise
limitations.
Journal of Hepatology 2015 vol. xxx j xxx–xxx 5
Please cite this article in press as: EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J
Hepatol (2015), http://dx.doi.org/10.1016/j.jhep.2015.04.006
respectively [59].
based on two physical principles: strain displacement/imaging
An important question in clinical practice is whether unreli- and shear wave imaging and quantification [88]. The latter allows
able results translate into decreased accuracy. It has been sug- a better estimation of liver tissue elasticity/stiffness, and includes
gested that among the recommendations, the IQR/M <30% is point shear wave elastography (pSWE), also known as acoustic
the most important parameter for good diagnostic accuracy radiation force impulse imaging (ARFI) (Virtual touch tissue
[60,61]. In a recent study [62] in 1165 patients with chronic quantification™, Siemens; elastography point quantification,
liver diseases (798 with chronic hepatitis C) taking liver biopsy ElastPQ™, Philips) and 2D-shear wave elastography (2D-SWE)
as reference, TE reliability was related to two variables in (Aixplorer™ Supersonic Imagine, France). pSWE/ARFI involves
multivariate analysis: the IQR/M and LS measure. Indeed, the
presence of an IQR/M >30% and LS measure median P7.1 kPa mechanical excitation of tissue using short-duration ($262 lsec)
resulted in a lower accuracy (as determined by AUROC) than
that of the whole study population and these cases were there- acoustic pulses that propagate shear waves and generate
fore considered ‘‘poorly reliable’’. Conversely, the highest accu-
racy was observed in the group with an IQR/M 610% localized, l-scale displacements in tissue [89]. The shear wave
regardless of the LS measure. Also a recent study reported a sig-
nificant discrepancy in up to 20% of cases in patients without velocity (expressed in m/sec) is measured in a smaller region
cirrhosis between different FibroScan devices (402 vs. 502) than in TE (10 mm long and 6 mm wide), but the exact location
[63]. These results require further validation before any recom- where measurements are obtained can be selected by the opera-
mendation can be made. tor under B-mode visualization. A major advantage of pSWE/ARFI
is that it can be easily implemented on modified commercial
In order to minimize the number of patients with unreli- ultrasound machines (Acuson 2000/3000 Virtual Touch™
able results due to obesity, a new probe (XL, 2.5 MHz trans- Tissue Quantification, Siemens Healthcare, Erlangen, Germany;
ducer), allowing measurement of LS between 35 to 75 mm ElastPQ, iU22xMATRIX, Philips, Amsterdam, The Netherlands).
depth, has been developed [64–68]. Myers et al. [66] showed Its failure rate is significantly lower than that of TE (2.9% vs.
that in 276 patients with chronic liver disease (42% viral hep- 6.4%, p <0.001), especially in patients with ascites or obesity
atitis, 46% NAFLD) and a BMI >28 kg/m2, measurement failures [90]. Also its reproducibility is good, with ICC ranging from 0.84
were significantly less frequent with the XL probe than with to 0.87 [91–93]. However, like TE, pSWE/ARFI results are influ-
the M probe (1.1% vs. 16%; p <0.00005). However, unreliable enced by food intake [94] as well as necro-inflammatory activity
results were still observed with the XL probe in 25% of case and the serum levels of aminotransferases [95], both of which
instead of 50% with the M probe (p <0.00005). Also it is lead to an overestimation of liver fibrosis and have to be taken
important to note that stiffness values obtained with XL probe into account when interpreting the results. LS values obtained
are lower than that obtained with the M probe (by a median with pSWE/ARFI, in contrast to TE values, have a narrow range
of 1.4 kPa). (0.5–4.4 m/sec). This limits the definitions of cut-off values for
discriminating certain fibrosis stages and thus for making
Apart from obese patients, TE results can also be difficult to management decisions. Finally, quality criteria for correct inter-
obtain from patients with narrow intercostal space and are pretation of pSWE results remain to be defined.
nearly impossible to obtain from patients with ascites [49]. As
the liver is an organ with a distensible but non-elastic envelope 2D-SWE is based on the combination of a radiation force
(Glisson’s capsule), additional space-occupying tissue abnor- induced in tissues by focused ultrasonic beams and a very high
malities, such as edema, inflammation, extra-hepatic cholestasis, frame rate ultrasound imaging sequence capable of catching in real
or congestion, can interfere with measurements of LS, indepen- time the transient propagation of resulting shear waves [96]. The
dently of fibrosis. Indeed, the risk of overestimating LS values size of the region of interest can be chosen by the operator.
has been reported with other confounding factors including ala- 2D-SWE has also the advantage of being implemented on a com-
nine aminotransferase (ALT) flares [69–71], extra-hepatic mercially ultrasound machine (AixplorerÒ, Supersonic Imagine,
cholestasis [72], congestive heart failure [73], excessive alcohol Aix en Provence, France) with results expressed either in m/sec
intake [74–76], and food intake [77–80], suggesting that TE or in kPa at a wide range of values (2–150 kPa). Its failure rate is
should be performed in fasting patients (for at least 2 h) and significantly lower than that of TE [97–99], particularly in patients
results always interpreted being aware of these potential con- with ascites [98,99], but not in obese patients when the XL probe is
founding [81]. The influence of steatosis is still a matter of used for TE (10.4% vs. 2.6%, respectively) [100]. Similar to pSWE/
debate with conflicting results: some studies suggest that ARFI, quality criteria for 2D-SWE remain to be defined.
steatosis is associated to an increase in LS [82–84] whereas
others do not [85,86]. MR elastography uses a modified phase-contrast method to
image the propagation characteristics of the shear wave in the
Other liver elasticity-based imaging techniques liver [101]. Elasticity is quantified by MR elastography (expressed
Several other liver elasticity-based imaging techniques are being in kPa) using a formula that determines the shear modulus,
developed, including ultrasound-based techniques and 3-D mag- which is equivalent to one-third the Young’s modulus used with
netic resonance (MR) elastography [87]. Ultrasound elastography TE [102]. The theoretical advantages of MR elastography include
can be currently performed by different techniques, which are its ability to analyze almost the entire liver and its good
applicability in patients with obesity or ascites. However, MR
elastography remains currently too costly and time-consuming
to be used in routine practice and cannot be performed in livers
of patients with iron overload, because of signal-to-noise
limitations.
Journal of Hepatology 2015 vol. xxx j xxx–xxx 5
Please cite this article in press as: EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J
Hepatol (2015), http://dx.doi.org/10.1016/j.jhep.2015.04.006
