Page 5 - NON-INVASIVE TESTS FOR EVALUATION OF LIVER DISEASE SEVERITY AND PROGNOSIS
P. 5
Clinical Practice Guidelines
Table 3. Respective advantages and disadvantages of currently available non-invasive methods in patients with chronic liver disease.
Serum biomarkers Measurement of liver stiffness
Advantages Transient elastography ARFI (pSWE) 2D-SWE MR elastography
• Good reproducibility
• High applicability (95%) • Most widely used and • Can be implemented on a • Can be implemented on a • Can be implemented on a
• No cost and wide availability validated technique: regular US machine regular US machine regular MRI machine
standard to be beaten
(non-patented) • ROI smaller than TE but • ROI can be adjusted in size • Examination of the whole
• Well validated • User-friendly (performed location chosen by the and location and chosen by liver
• Can be performed in the at bedside; rapid, easy to operator the operator
learn) • Higher applicability than
outpatient clinic • Higher applicability than TE • Measures liver stiffness in TE (ascites and obesity)
• High range of values (2-75 (ascites and obesity) real-time
Disadvantages kPa) • High performance for
• Non-specific of the liver • Performance equivalent • High range of values (2-150 cirrhosis
• Unable to discriminate • Quality criteria well defined to that of TE for significant kPa)
• Good reproducibility fibrosis and cirrhosis
between intermediate stages • High performance for • Good applicability
of fibrosis • High performance for
• Performance not as good as cirrhosis (AUROC >0.9)
TE for cirrhosis • Prognostic value in cirrhosis
• Cost and limited availability
(proprietary) cirrhosis
• Limitations (hemolysis,
Gilbert syndrome, • Requires a dedicated • Unable to discriminate • Further validation warranted • Further validation
inflammation…) device between intermediate • Unable to discriminate warranted especially in
stages of fibrosis comparison with TE
• ROI cannot be chosen between intermediate
• Unable to discriminate • Units (m/sec) different from stages of fibrosis • Not applicable in case of
that of TE (kPa) • Quality criteria not well iron overload
between intermediate defined
stages of fibrosis • Narrow range of values • Learning curve? • Requires a MRI facility
• Applicability (80%) lower • (0.5-4.4 m/sec) • Influence of inflammation? • Time-consuming
than serum biomarker: • Quality criteria not well • Costly
(obesity, ascites, operator
experience) defined
• False positive in case of • Prognostic value in
acute hepatitis, extra-
hepatic cholestasis, liver cirrhosis?
congestion, food intake and
excessive alcohol intake
ROI, region of interest.
velocity of a low-frequency (50 Hz) elastic shear wave propagat- measurements) less than 30% of the median LS measurements
ing through the liver. This velocity is directly related to tissue (M) value (IQR/M 60.30%) [50].
stiffness, called the elastic modulus (expressed as E = 3 qv2, The results are expressed in kilopascals (kPa), and range from
where v is the shear velocity and q is the density of tissue, 1.5 to 75 kPa with normal values around 5 kPa, higher in men and
in patients with low or high body mass index (BMI) (U-shaped
assumed to be constant). The stiffer the tissue, the faster the distribution) [51–54].
shear wave propagates.
Advantages of TE include a short procedure time (<5 min),
TE is performed on a patient lying supine, with the right arm immediate results, and the ability to perform the test at the bed-
elevated to facilitate access to the right liver lobe. The tip of the side or in an outpatient clinic (Table 3). Finally, it is not a difficult
probe is contacted to the intercostal skin with coupling gel in procedure to learn which can be performed by a nurse or a tech-
the 9th to 11th intercostal space at the level where a liver biopsy nician after minimal training (about 100 examinations) [55].
would be performed. The operator, assisted by a time-motion Nevertheless, the clinical interpretation of TE results should
image, locates a liver portion at least 6 cm deep and free of large always be in the hands of an expert clinician and should be made
vascular structures. The operator then presses the probe button with full knowledge of patient demographics, disease etiology
to start the measurements (‘‘shots’’). TE measures LS in a volume and essential laboratory parameters.
that approximates a cylinder 1 cm wide and 4 cm long, between
25 mm and 65 mm below the skin surface. The software deter- Although TE analysis has excellent inter- and intra-observer
mines whether each measurement is successful or not. When a agreement [56,57] (with an intra-class correlation coefficient
shot is unsuccessful, the machine does not return a value. The (ICC) of 0.98), its applicability is not as good as that of serum bio-
entire procedure is considered to have failed when no value is markers. In the largest TE series reported to date (n = 13,369
obtained after ten shots. The final result of a TE session can be examinations), failure to obtain any measurement has been
regarded as valid if the following criteria are fulfilled: 1) a num- reported in 3.1% of cases and unreliable results (not meeting
ber of valid shots of at least 10; 2) a success rate (the ratio of valid manufacturer’s recommendations) in 15.8% [58], mostly due to
shots to the total number of shots) above 60%; and 3) an patient obesity or limited operator experience. Similar results
interquartile range (IQR, reflecting the variability of have been reported in a large series of Asian patients (n = 3205)
4 Journal of Hepatology 2015 vol. xxx j xxx–xxx
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
Table 3. Respective advantages and disadvantages of currently available non-invasive methods in patients with chronic liver disease.
Serum biomarkers Measurement of liver stiffness
Advantages Transient elastography ARFI (pSWE) 2D-SWE MR elastography
• Good reproducibility
• High applicability (95%) • Most widely used and • Can be implemented on a • Can be implemented on a • Can be implemented on a
• No cost and wide availability validated technique: regular US machine regular US machine regular MRI machine
standard to be beaten
(non-patented) • ROI smaller than TE but • ROI can be adjusted in size • Examination of the whole
• Well validated • User-friendly (performed location chosen by the and location and chosen by liver
• Can be performed in the at bedside; rapid, easy to operator the operator
learn) • Higher applicability than
outpatient clinic • Higher applicability than TE • Measures liver stiffness in TE (ascites and obesity)
• High range of values (2-75 (ascites and obesity) real-time
Disadvantages kPa) • High performance for
• Non-specific of the liver • Performance equivalent • High range of values (2-150 cirrhosis
• Unable to discriminate • Quality criteria well defined to that of TE for significant kPa)
• Good reproducibility fibrosis and cirrhosis
between intermediate stages • High performance for • Good applicability
of fibrosis • High performance for
• Performance not as good as cirrhosis (AUROC >0.9)
TE for cirrhosis • Prognostic value in cirrhosis
• Cost and limited availability
(proprietary) cirrhosis
• Limitations (hemolysis,
Gilbert syndrome, • Requires a dedicated • Unable to discriminate • Further validation warranted • Further validation
inflammation…) device between intermediate • Unable to discriminate warranted especially in
stages of fibrosis comparison with TE
• ROI cannot be chosen between intermediate
• Unable to discriminate • Units (m/sec) different from stages of fibrosis • Not applicable in case of
that of TE (kPa) • Quality criteria not well iron overload
between intermediate defined
stages of fibrosis • Narrow range of values • Learning curve? • Requires a MRI facility
• Applicability (80%) lower • (0.5-4.4 m/sec) • Influence of inflammation? • Time-consuming
than serum biomarker: • Quality criteria not well • Costly
(obesity, ascites, operator
experience) defined
• False positive in case of • Prognostic value in
acute hepatitis, extra-
hepatic cholestasis, liver cirrhosis?
congestion, food intake and
excessive alcohol intake
ROI, region of interest.
velocity of a low-frequency (50 Hz) elastic shear wave propagat- measurements) less than 30% of the median LS measurements
ing through the liver. This velocity is directly related to tissue (M) value (IQR/M 60.30%) [50].
stiffness, called the elastic modulus (expressed as E = 3 qv2, The results are expressed in kilopascals (kPa), and range from
where v is the shear velocity and q is the density of tissue, 1.5 to 75 kPa with normal values around 5 kPa, higher in men and
in patients with low or high body mass index (BMI) (U-shaped
assumed to be constant). The stiffer the tissue, the faster the distribution) [51–54].
shear wave propagates.
Advantages of TE include a short procedure time (<5 min),
TE is performed on a patient lying supine, with the right arm immediate results, and the ability to perform the test at the bed-
elevated to facilitate access to the right liver lobe. The tip of the side or in an outpatient clinic (Table 3). Finally, it is not a difficult
probe is contacted to the intercostal skin with coupling gel in procedure to learn which can be performed by a nurse or a tech-
the 9th to 11th intercostal space at the level where a liver biopsy nician after minimal training (about 100 examinations) [55].
would be performed. The operator, assisted by a time-motion Nevertheless, the clinical interpretation of TE results should
image, locates a liver portion at least 6 cm deep and free of large always be in the hands of an expert clinician and should be made
vascular structures. The operator then presses the probe button with full knowledge of patient demographics, disease etiology
to start the measurements (‘‘shots’’). TE measures LS in a volume and essential laboratory parameters.
that approximates a cylinder 1 cm wide and 4 cm long, between
25 mm and 65 mm below the skin surface. The software deter- Although TE analysis has excellent inter- and intra-observer
mines whether each measurement is successful or not. When a agreement [56,57] (with an intra-class correlation coefficient
shot is unsuccessful, the machine does not return a value. The (ICC) of 0.98), its applicability is not as good as that of serum bio-
entire procedure is considered to have failed when no value is markers. In the largest TE series reported to date (n = 13,369
obtained after ten shots. The final result of a TE session can be examinations), failure to obtain any measurement has been
regarded as valid if the following criteria are fulfilled: 1) a num- reported in 3.1% of cases and unreliable results (not meeting
ber of valid shots of at least 10; 2) a success rate (the ratio of valid manufacturer’s recommendations) in 15.8% [58], mostly due to
shots to the total number of shots) above 60%; and 3) an patient obesity or limited operator experience. Similar results
interquartile range (IQR, reflecting the variability of have been reported in a large series of Asian patients (n = 3205)
4 Journal of Hepatology 2015 vol. xxx j xxx–xxx
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
