ShearWave™ Elastography in Chronic Liver Diseases: Clinical Research Literature Review

1 /27 SWE™ in Chronic Liver Diseases Published Results from Clinical Research

ShearWave™ Elastography

in Chronic Liver Diseases

CLINICAL RESEARCH LITERATURE REVIEW

BY JOEL GAY, CLINICAL MANAGER

SUPERSONIC IMAGINE


Preamble

• Clinical information is presented along with the source references for informational purposes only. This information is available in peer-reviewed published journals and represents the findings of the third-party and not of SuperSonic Imagine. Research findings do not represent any claims by SuperSonic Imagine.

• This presentation contains information and images which are provided as an information resource only, and are not to be used or relied on for any diagnostic or treatment purposes.

• None of the Company, Managers of affiliates, members, directors, officers or employees accepts liability for any loss arising from the use of this presentation or contents arising in connection therewith.

• Third-party or customers quotes represent the opinion of the third-party and are not to be considered as claims nor the opinion of SuperSonic Imagine.

• This presentation is not to be used as a source of patients education.

• Aixplorer® is an ultrasound imaging equipment for diagnostic use, allowing to perform anatomical and morphological imaging, blood flow imaging, and elasticity imaging of soft tissue.

• Aixplorer® must be operated by experienced & trained personnel, in order to collect information that will be interpreted by a medical doctor (radiologist or clinician), while taking into account all clinical information available in the patient’s file.

• Aixplorer® is NOT providing a diagnosis, but important and relevant information to enable a medical doctor to make a diagnosis.

• Aixplorer® is a CE-marked Class IIa medical device (CE Certificate #26415).

• Current Intended Use cleared by the FDA• “The SuperSonic Imagine AIXPLORER® ultrasound

system and transducer are intended for general purpose pulse echo ultrasound imaging, Doppler fluid flow analysis of the human body, and tissue elasticity imaging of soft tissues.” (K132274; K161999)

• “Diagnostic ultrasound imaging or fluid flow analysis of the human body.” (K132274; K142100)


Agenda

#1Liver Stiffness Measurement

•Technical Landscape

•Confounders

#2SWE™ Success Rate, Reliability and Reproducibility

•Healthy subjects

•Chronic hepatopathies

•Cirrhotic patients

•Protocol

#3Evaluation of Liver Fibrosis

•Stiffness of healthy liver

•Correlation of SWE with liver fibrosis

•Diagnostic performances

#4Prognostic Information

•Cirrhosis severity

•Portal hypertension

•Esophageal varices

#5Treatment Planning and Follow-up

•Liver transplantation

•Anti-viral treatments

•Monitoring of portal hypertension


Shear Wave-based Elastography:

Technical Landscape

SWE

External

Mechanical piston

Transient

elastography

1D

No SW propagation image

PQ

elastography LiveFrozen

External

Mechanical vibrator

A posteriori 2D MRE

2D

SW propagation imaging

Transient

vibration

Continuous

vibration

Continuous

Supersonic Shear ImagingComb-pushARFIndividual ARF

Internal

Acoustic Radiation Force

MRIUltrasound


Network of Confounding Factors of Liver

Fibrosis Assessment with Liver StiffnessCui XW et al. World J Gastroenterol. 2013 Oct 14;19(38):6329-47.

Liver

stiffnessLiver fibrosis

Breathing

Device /

Technology

Gender

Blood

pressure

BMI

Fasting

Lobe

Patient's

position

Steatosis

Congestion

Necro-inflammatory

activity

Age

Albumin

Cytolysis

Etiology

?

Prothrombin

Time

Platelets count

Total Bilirubin


Confounding Factors of Liver Stiffness

Measurement FailureCassinotto C et al. J Hepatol. 2014 Sep;61(3):550-7

Practice Patient

Failure of

breath control

Ultrasound

reverberation

Diabetes

BMI

Sub-optimal

acoustic window

Liver lobe

Patient's

positioning

Steatosis

Haptoglobin

Arterial

hypertension

Alkaline

PhosphataseAscites +++

Cardiac

pulsatility

Intercostal

wall thickness


SWE™ Technical Success Rates

(TSR) Reported in 12 Studies

Author, Journal YearNb

SubjectsLiver Disease TSR (%)

Ferraioli, EJR 2012 46 Healthy 91.3

Ferraioli, Hepatol 2012 121 HCV 97.5

Huang, WJG 2014 112 HBV 100

Leung, Radiol 2013 454 HBV 98.9

Cassinotto, Hepatol 2016 291 NASH 87

Gerber, UMB 2015 120 CLD 100

Guibal, Diag Interv Imaging 2016 170 CLD 89.5

Choi, Ultrasonics 2016 380 CLD 91.1

Yoneda, Clin Gastroenterol Hepatol 2015 124 CLD; BMI 25 kg/m² 94.6

Elkrief, Radiol 2014 77 Cirrhosis 99

Procopet, J Hepatol 2015 88 Cirrhosis 99

Cassinotto, Dig Liv Dis 2015 401 Cirrhosis 93.8


SWE™ Measurements Reliability

and Applicability

• Reliability criteria used/defined

• Image stability over 3-5 seconds (Cassinotto)

• Emin ≥ 0.2 kPa (Poynard)

• SD < 1.75 kPa and Q-Box™ > 18 mm (Thiele)

• SD3/Median3 < 10% or Depth of measurement < 5.6 cm (Elkrief)

• IQR/Median ≤ 30% (Yoon) or SD/Mean < 30% (Bota)

Author, Journal Year Nb Patients Liver DiseaseReliability or

Applicability (%)

Bota , UMB 2015 * 127 CLD 99.2

Poynard, PLosOne 2016 * 2251 CLD 89.6

Yoon, JUM 2014 454 CLD 83.7

Cassinotto, J Hepatol 2014 349 CLD 89.6

Cassinotto, Hepatol 2016 291 NASH 79.7

Elkrief, Radiol 2014 77 Cirrhosis 83

* No biopsy performed


Optimal Conditions for Liver

SWE Measurements

Determination of Conditions

• Elastometry Experience feedback

• Several published works:• Depth of measurements:

− Wang CZ et al. Ultrasound Med Biol. 2014 Mar;40(3):461-9.

• Liver lobe / segments:− Hudson JM et al. Ultrasound Med Biol. 2013

Jun;39(6):950-5.

− Gerber et al. Ultrasound Med Biol. 2015 Sep;41(9):2350-9.

− Yoneda M et al. Clin Gastroenterol Hepatol. 2015 Aug;13(8):1502-9.e5.

− Samir A et al. Radiology. 2015 Mar;274(3):888-96.

− Beland MD et al. AJR Am J Roentgenol. 2014 Sep;203(3):W267-73.

• Patient’s positioning:− Ferraioli G et al. Hepatology. 2012 Dec;56(6):2125-33.

− Cassinotto C et al. J Hepatol. 2014 Sep;61(3):550-7.

• Number of measurements:− Choi SH et al. Ultrasonics 2016;72:158-164

− Huang ZP et al. World J Gastroenterol 2014 July 28; 20(28): 9578-9584

− Vilgrain V et al. ESGAR 2015

• Other factors:− Huang Z et al. Ultrasound Med Biol. 2014

Nov;40(11):2549-55

Imaging Protocol

• Patient in supine position

• Right arm in maximal abduction

• Suspended breath (3-5 s)

• Right liver lobe (Segment 6-8)

• Intercostal approach

• SWE Box 3.5 x 2.5 cm

• 3 to 5 cm from the probe surface

• 1 to 2 cm below the liver capsule

• Q-Box™ diameter: 20 mm

• Pressure +++ on thoracic wall

• Maximize probe contact and ultrasound transmission (ultrasound gel)

• Orthogonal to liver capsule

• At least 3 independent measurements


SWE Measurements

Reproducibility

Author, Journal Year

Nb Meas.

Nb Op.

Nb Sess.

Nb Subj. Intra-Op ICCInter-Session

ICCInter-Operator

ICC

Ferraioli, EJR 2012 10 2 2 42 healthyExpert: 0.95Novice: 0.93

Expert: 0.84Novice: 0.65

0.88

Hudson, UMB 2013

5 2 215 healthySegt 6

Op1: 0.91Op2: 0.92

Op1: 0.63Op2: 0.84

0.83

Yoon, JUM 2014 15 1 2454 patients

2 meas: 0.936 meas: 0.96

0.95Fatty liver: 0.83CLD: 0.88Cirrhosis: 0.96

Cassinotto, Dig Liver Dis 2015

5 2 1401 cirrhotic patients

Liver: 0.95Spleen: 0.96

N/ALiver: 0.94

Spleen: 0.87

Thiele, EJU 2016 5 1 1 142 0.95 N/A N/A


Stiffness Value of Healthy Liver

• Experience reported in 18 peer-reviewed publications, from January 2009 until

September 2015

• Publications with kPa values

• Healthy volunteers: 9 articles

• F0-F1 patients with chronic liver diseases: 8 articles

• Reported values

• Healthy liver: Emean= 4.99+/-1.39 kPa

• F0-F1 : Emean= 6.74+/-1.95

3

4

5

6

7

8

9

Status

Avera

ge

CLD HLT

Median values, IQR and extreme

values in healthy subjects (HLT)

and F0-F1 patients with chronic

liver diseases (CLD)


References

SWE Values (kPa) in healthy

subjects1. Quantitative assessment of the elasticity values of liver with shear wave ultrasonographic

elastography. Arda K, Ciledag N, Aribas BK, Aktas E, Köse K. Indian J Med Res. 2013

May;137(5):911-5.

2. Reproducibility of real-time shear wave elastography in the evaluation of liver elasticity. Ferraioli G,

Tinelli C, Zicchetti M, Above E, Poma G, Di Gregorio M, Filice C. Eur J Radiol. 2012

Nov;81(11):3102-6.

3. 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. Franchi-Abella S, Corno L,

Gonzales E, Antoni G, Fabre M, Ducot B, Pariente D, Gennisson JL, Tanter M, Corréas JM.

Radiology. 2016 Feb;278(2):554-62.

4. Inter- and intra-operator reliability and repeatability of shear wave elastography in the liver: a study in

healthy volunteers. Hudson JM, Milot L, Parry C, Williams R, Burns PN. Ultrasound Med Biol. 2013

Jun;39(6):950-5.

5. 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.

Leung VY, Shen J, Wong VW, Abrigo J, Wong GL, Chim AM, Chu SH, Chan AW, Choi PC, Ahuja AT,

Chan HL, Chu WC. Radiology. 2013 Dec;269(3):910-8.

6. Determination of normal hepatic elasticity by using real-time shear-wave elastography. Suh CH, Kim

SY, Kim KW, Lim YS, Lee SJ, Lee MG, Lee J, Lee SG, Yu E. Radiology. 2014 Jun;271(3):895-900.

7. Influence of measurement depth on the stiffness assessment of healthy liver with real-time shear

wave elastography. Wang CZ, Zheng J, Huang ZP, Xiao Y, Song D, Zeng J, Zheng HR, Zheng RQ.

Ultrasound Med Biol. 2014 Mar;40(3):461-9.

8. Staging of hepatic fibrosis: comparison of magnetic resonance elastography and shear wave

elastography in the same individuals. Yoon JH, Lee JM, Woo HS, Yu MH, Joo I, Lee ES, Sohn JY,

Lee KB, Han JK, Choi BI. Korean J Radiol. 2013 Mar-Apr;14(2):202-12.

9. Shear wave elastography for liver stiffness measurement in clinical sonographic examinations:

evaluation of intraobserver reproducibility, technical failure, and unreliable stiffness measurements.

Yoon JH, Lee JM, Han JK, Choi BI. J Ultrasound Med. 2014 Mar;33(3):437-47.

SWE Values (kPa) in patients with

F0-F1 CLD1. Non-invasive assessment of liver fibrosis with impulse elastography: comparison of Supersonic Shear

Imaging with ARFI and FibroScan®. 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. J

Hepatol. 2014 Sep;61(3):550-7.

2. Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: a

pilot study. Ferraioli G, Tinelli C, Dal Bello B, Zicchetti M, Filice G, Filice C; Liver Fibrosis Study

Group. Hepatology. 2012 Dec;56(6):2125-33.

3. Assessment of liver fibrosis with 2-D shear wave elastography in comparison to transient

elastography and acoustic radiation force impulse imaging in patients with chronic liver disease.

Gerber L, Kasper D, Fitting D, Knop V, Vermehren A, Sprinzl K, Hansmann ML, Herrmann E, Bojunga

J, Albert J, Sarrazin C, Zeuzem S, Friedrich-Rust M. Ultrasound Med Biol. 2015 Sep;41(9):2350-9.

4. Normal liver stiffness in healthy adults assessed by real-time shear wave elastography and factors

that influence this method. Huang Z, Zheng J, Zeng J, Wang X, Wu T, Zheng R. Ultrasound Med Biol.

2014 Nov;40(11):2549-55.

5. Real time shear wave elastography in chronic liver diseases: accuracy for predicting liver fibrosis, in

comparison with serum markers. Jeong JY, Kim TY, Sohn JH, Kim Y, Jeong WK, Oh YH, Yoo KS.

World J Gastroenterol. 2014 Oct 14;20(38):13920-9.

6. Shear-wave elastography for the estimation of liver fibrosis in chronic liver disease: determining

accuracy and ideal site for measurement. Samir AE, Dhyani M, Vij A, Bhan AK, Halpern EF, Méndez-

Navarro J, Corey KE, Chung RT. Radiology. 2015 Mar;274(3):888-96.

7. Supersonic Shear Imaging and Transient Elastography With the XL Probe Accurately Detect Fibrosis

in Overweight or Obese Patients With Chronic Liver Disease. Yoneda M, Thomas E, Sclair SN, Grant

TT, Schiff ER. Clin Gastroenterol Hepatol. 2015 Aug;13(8):1502-9.e5.

8. Diagnostic accuracy of two-dimensional shear wave elastography for the non-invasive staging of

hepatic fibrosis in chronic hepatitis B: a cohort study with internal validation. Zeng J, Liu GJ, Huang

ZP, Zheng J, Wu T, Zheng RQ, Lu MD. Eur Radiol. 2014 Oct;24(10):2572-81.


Correlation of SWE™ Values with METAVIR

Stages in Chronic HBV PatientsZeng J et al. Eur Radiol. 2014 Oct;24(10):2572-81.

Validation cohort

Development cohort

• 372 patients recruited, of which 310 finally included• 206 in development cohort

• 104 in validation cohort

• SWE™ Protocol• Patients in supine position, with right

arm in maximum abduction

• SWE acquisitions and measurements on the right liver via intercostal access

• Breath hold during 5 seconds

• SWE Box of 4 cm×3 cm size, placed 1 cm below the capsule

• Q-Box™ with the largest diameter possible, avoiding vessels

• 5 measurements per patient

• Technical success rate: 306/310 (98.7%)


Diagnostic Performances (AUROC) in

HBV PatientsZeng J et al. Eur Radiol. 2014 Oct;24(10):2572-81.


AUROCs in Patients with Mixed

Etiologies in Comparative Studies

Cassinotto C et al. J Hepatol. 2014 Sep;61(3):550-7.

Gerber L et al. Ultrasound Med Biol. 2015 Sep;41(9):2350-9. (Per protocol assessment)

Yoneda M et al. Clin Gastroenterol Hepatol. 2015 Aug;13(8):1502-9. (Patients with BMI > 25 kg/m²)

Herrmann et al. J Hepatol 2015 Apr;62:S187–S212. (Oral presentation at EASL 2015, manuscript submitted)

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

Yoneda, 2015 Herrmann, 2015 Cassinotto, 2014 Gerber, 2015 Yoneda, 2015 Herrmann, 2015 Cassinotto, 2014 Gerber, 2015 Yoneda, 2015 Herrmann, 2015 Cassinotto, 2014 Gerber, 2015

≥F2 ≥F3 F4

Mixed etiologies SWE0.86


AUROCs in Patients with Chronic

HCV in Comparative Studies

Bavu E et al. Ultrasound Med Biol. 2011 Sep;37(9):1361-73.

Ferraioli G et al. Hepatology. 2012 Dec;56(6):2125-33.

Yoneda M et al. Clin Gastroenterol Hepatol. 2015 Aug;13(8):1502-9. (Patients with BMI > 25 kg/m²)


0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

Bavu, 2011 Ferraioli, 2012 Yoneda, 2015 Herrmann, 2015 Bavu, 2011 Ferraioli, 2012 Yoneda, 2015 Herrmann, 2015 Bavu, 2011 Ferraioli, 2012 Yoneda, 2015 Herrmann, 2015

≥F2 ≥F3 F4

HCV SWE0.86


AUROCs in Patients with Chronic

HBV in Comparative Studies

Leung VY et al. Radiology. 2013 Dec;269(3):910-8.


0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

Leung, 2013 Herrmann, 2015 Leung, 2013 Herrmann, 2015 Leung, 2013 Herrmann, 2015

≥F2 ≥F3 F4

HBV SWE0.88


AUROCs in Patients with NAFLD and

NASH in Comparative Studies


Cassinotto et al. Hepatology. 2016 Jun;63(6):1817-27.

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

Herrmann, 2015 Cassinotto, 2016 Herrmann, 2015 Cassinotto, 2016 Herrmann, 2015 Cassinotto, 2016

≥F2 ≥F3 F4

NAFLD SWE0.86


3 Meta-analyzes on SSI-SWE

Published in 2016

Authors, Journal Year Search date QUADASNb

articlesNb

patients

≥ F2AUROC (95% CI)Sensitivity (%; 95%CI)Specificity (%; 95%CI)

F4AUROC (95% CI)Sensitivity (%; 95%CI)Specificity (%; 95%CI)

Feng, JUM 2016 February 28, 2015 Yes 12 16350.85 (0.81-0.88)84 (81-86)81 (74-87)

0.93 (0.90-0.95)88 (82-91)86 (81-90)

Jiang, PLosOne 2016 May 13, 2016 Yes 13 23030.87 (0.84-0.90)84 (81-86)83 (77-88)

0.94 (0.92-0.96)89 (84-92)88 (84-92)

Li, Med Sci Monit 2016 N/A Yes 8 9340.88 (0.85-0.91)85 (82-88)81 (71-88)

0.92 (0.89-0.94)87 (80-92)88 (80-93)


Multicenter Retrospective Analysis

Results Presented at EASL 2015Submitted data

• Information collected retrospectively from 13 sites in Europe and Asia, having used or using SWE™ for liver fibrosis assessment

• 1650 patients

• “Real-life” conditions corresponding to routine practice

• Statistical analysis performed independently by Prof Eva Herrmann, Univ Frankfurt, taking into account the heterogeneity of data between sites.

• EASL 2015 #RS-3186: 2D-Shear Wave Elastography is Equivalent or Superior to Transient Elastography for Liver Fibrosis Assessment: Results from an Individual Patient Data Based Meta-analysis• 1340 patients with SWE

• 972 patients in a comparative sub-study

• Objective: To assess the diagnostic performances of SWE to evaluate severity of liver fibrosis, depending on liver disease etiology

• Etiologies

• HCV: n=470

• HBV: n=420

• NAFLD/NASH: n=172

• Others: n=278

Fibrosis severity

HCV HBVNAFLD/NASH

METAVIR ≥ F2

AUROC (%) 86.3 91.6 85.9

Cutoff (kPa) 7.1 7.1 7.1

METAVIR = F4

AUROC (%) 96.1 97.1 95.5

Cutoff (kPa) 13.5 11.5 13.5


3 3,5 4 4,5 5 5,5 6 6,5 7 7,5 8 8,5 9 9,5 10 10,5 11 11,5 12 12,5 13 13,5 14 14,5 15 15,5 16 16,5 17

3 3,5 4 4,5 5 5,5 6 6,5 7 7,5 8 8,5 9 9,5 10 10,5 11 11,5 12 12,5 13 13,5 14 14,5 15 15,5 16 16,5 17

SWE™ Liver Stiffness Cutoff Values for the

Assessment of Liver Fibrosis Severity and

their Performances

HCV Patients

References :

1. Reproducibility of real-time shear wave elastography in the evaluation of liver elasticity. Ferraioli G et al. Eur J Radiol. 2012 Nov;81(11):3102-6.

2. Inter- and intra-operator reliability and repeatability of shear wave elastography in the liver: a study in healthy volunteers. Hudson JM et al. Ultrasound Med Biol. 2013 Jun;39(6):950-5.

3. Staging of hepatic fibrosis: comparison of magnetic resonance elastography and shear wave elastography in the same individuals. Yoon JH et al. Korean J Radiol. 2013 Mar-Apr;14(2):202-12.

4. Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: a pilot study. Ferraioli G et al. Hepatology. 2012 Dec;56(6):2125-33

5. Supersonic Shear Imaging and Transient Elastography With the XL Probe Accurately Detect Fibrosis in Overweight or Obese Patients With Chronic Liver Disease. Yoneda M, Thomas E, Sclair SN, Grant

TT, Schiff ER. Clin Gastroenterol Hepatol. 2015 Aug;13(8):1502-9.e5.

6. 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. Leung

VY et al. Radiology. 2013 Dec;269(3):910-8.

7. Diagnostic accuracy of two-dimensional shear wave elastography for the non-invasive staging of hepatic fibrosis in chronic hepatitis B: a cohort study with internal validation. Zeng J, Liu GJ, Huang ZP,

Zheng J, Wu T, Zheng RQ, Lu MD. Eur Radiol. 2014 Oct;24(10):2572-81.

8. Liver stiffness in nonalcoholic fatty liver disease: A comparison of Supersonic Shear Imaging, FibroScan and ARFI with liver biopsy. Cassinotto C, Boursier J, De Ledinghen V, Lebigot J, Lapuyade B,

Cales P, Hiriart JB, Michalak S, Le Bail B, Cartier V, Mouries A, Oberti F, Fouchard-Hubert I, Vergniol J, Aube C. Hepatology. 2015 Dec 13. doi: 10.1002/hep.28394.

9. Transient and 2-Dimensional Shear-Wave Elastography Provide Comparable Assessment of Alcoholic Liver Fibrosis and Cirrhosis. Thiele M, Detlefsen S, Sevelsted Møller L, Madsen BS, Fuglsang

Hansen J, Fialla AD, Trebicka J, Krag A. Gastroenterology. 2016 Jan;150(1):123-33.

Se: 83.9%

Sp: 83.3%

Se: 90.7%

Sp: 88.9%

Se: 72.5%

Sp: 96.4%

Se: 75.8%

Sp: 83.3%

Se: 87.5%

Sp: 96.8%

Se: 97.3%

Sp: 95.1%

Se: 90.0%

Sp: 87.5%

No disease1-3 F2 F3 F4F0-F1Color legend:

Unspecified BMI [4]

BMI > 25 kg/m² [5]

HBV Patients[6-7] Se: 91.9%

Sp: 89.7%

Se: 91.9%

Sp: 85.7%

Se: 86.4%

Sp: 86.9%

Se: 83.5%

Sp: 91.2%

NAFLD Patients[8]

Se: 90%

Sp: 72%Se: 91%

Sp: 71%

Se: 90%

Sp: 50%

Se: 58%

Sp: 90%

Se: 71%

Sp: 90%

Se: 71%

Sp: 90%

Sensitivity ≥ 90%

Specificity ≥ 90%

ALD Patients[9*] Se: 100%

Sp: 96%

Se: 92%

Sp: 81%

* Cut-off values in a high-risk population, with a prevalence of significant fibrosis > 50% and a prevalence of cirrhosis > 25% would be 10,1 kPa dna 16,4 kPa, respectively.

F1


Prognostic Information in

Cirrhotic Patients

• Prediction of liver failure in HBV/HCV patientsGrgurevic I et al. Eur Radiol. 2015 Nov;25(11):3214-21.

• 123 patients

• SWE Protocol− Right liver, intercostal access

− 5 measurements performed

• Liver stiffness > 27 kPa− Sensitivity: 90.5%

− Specificity: 96.2%

• Spleen stiffness (measured via left intercostal access) can be used as well, but is more challenging with higher failure rate (~40%)

Cassinotto, Dig Liver Dis. 2015 Aug;47(8):695-701.

Correlation between liver stiffness and cirrhosis clinical

severity

Cutoff values defined to provide a NPV ≥ 90%

Cassinotto, Dig Liver Dis. 2015 Aug;47(8):695-701.


Non-Invasive Diagnosis of Clinically

Significant Portal Hypertension (CSPH)

AuthorNb pts

Nb Meas

Organ Correl coef AUROC Cutoff value (kPa)Sensitivity

(%)Specificity

(%)

Elkrief 77 3 Liver 0.578 (p<0.0001) 0.79 24.5 81 88

Procopet 88 3 Liver 0.611 (p<0.0001) 0.72 2-cutoff strategy N/A N/A

Elkrief 77 3 Spleen 0.604 (p=0.088) 0.86 34.7 40 100

Procopet 88 3 Spleen 0.514 (p<0.0001) 0.73 N/A N/A N/A

• Proposal for clinical implementation by Procopet et al.:

• Liver stiffness < 14.1 kPa can exclude CSPH

• Liver stiffness >25.8 kPa can predict CSPH

• 65% of patients would be classified, of which 89% correctly

• Spleen stiffness measurements can be considered in addition to liver stiffness, but technique is more challenging with technical success rates between 60% and 70%.


Algorithm to Rule Out CSPHJansen et al. Gut. 2016 Jun;65(6):1057-8.

Jansen et al. Liver Int. 2016 Aug 29. doi: 10.1111/liv.13243

• Objective was to define an

algorithm to diagnose non-

invasively patients with and without

CSPH

• Algorithm using

• Liver SWE stiffness

• Spleen SWE stiffness

• 158 patients with mixed etiologies

• 56% ASH

• 17% NASH

• 8% HBV

• 19% Others Sensitivity Specificity PPV NPV Accuracy

98.6% 70.3% 86.6% 96.3% 89%


Prediction of Esophageal VaricesKim et al. JUM 2016;35:1373-1381

• Retrospective study on 103 patients with compensated cirrhosis recruited for upper endoscopy

• SWE acquisitions and measurements protocol• Fasting patients for 8 hours

• Supine position with right arm in maximum abduction

• SWE Box located 2 cm below the liver capsule

• Suspended expiration for 5 seconds

• Adjusted Q-Box™ up to a max diameter of 20 mm

• 5 acquisitions and 5 measurements (median, IQR and IQR/median)

• Prediction of varices

• Prediction of high-risk varices

ParameterAUROC(95% CI)

CutoffSens(%)

Spec(%)

Platelets(103/mm3)

0.845(0.761-0.909)

89 85 81

Spleen size(cm)

0.722(0.625-0.806)

13.7 54 93

Platelets/Spleen size(N/mm3/mm)

0.841(0.755-0.905)

824 85 80

Liver SWE(kPa)

0.880(0.801-0.936)

16.1 85 86

ParameterAUROC(95% CI)

CutoffSens(%)

Spec(%)

Platelets(103/mm3)

0.765(0.672-0.843)

104 70 76

Spleen size(cm)

0.692(0.594-0.780)

10.7 68 68

Platelets/Spleen size(N/mm3/mm)

0.770(0.677-0.848)

860 63 83

Liver SWE(kPa)

0.887(0.809-0.941)

13.9 75 89


Transplantation Planning and

Monitoring

• Objective: To compare liver stiffness values measured with SWE™ and MRE in patients with chronic liver diseasesYoon et al. Korean J Radiol. 2013 Mar-Apr;14(2):202-12.

• Subjects:

• 94 pre-transplantation patients

• 114 living donors

• SWE Measurements protocol

• Right liver via intercostal access

• 5 measurements

• Depth between 25 and 45 mm

• EMean < 5.6 kPa seemed to be a good indicator to exclude the very early stages of fibrosis (F0)

• Sensitivity=100%

• Specificity=90%

• Possible utility to select living donors

• Objective: To evaluate liver graft failure or post-transplantation recurring disease with SWE™.Yoon et al. Eur Radiol. 2013 Jun;23(6):1729-37

• Subjects:• 216 pre-transplantation patients

• 37 living donors

• SWE Measurements protocol• Right liver via intercostal access

• 5 measurements

• 15 to 20 mm below the capsule

• Liver graft failure/rejection or post-transplantation recurring disease could be predicted with SWE™ measurements.• Liver transplant stiffness should be

measured 4 weeks after transplantation

• EMean < 8 kPa could exclude the hypothesis of a graft failure or of recurring disease (specificity=87%)


Therapeutic Monitoring and

Follow-up

• Monitoring of portal hypertension (PH)Choi SY et al. Radiology. 2014 Dec;273(3):917-26.

• 105 patients with portal hypertension, of which 23 were followed-up (average follow-up duration was 174+/-19 days)

• SWE Protocol

• Right liver via intercostal access

• Normal breath hold

• 5 measurements with Q-Box™ of 20 mm diameter

• Strong correlation between D SWE liver stiffness and D HVPG: (r=0.863)

• Increase in SWE values was highly predictive of PH worsening(AUROC: 0.925)

• Prediction of hepatocellular carcinoma (HCC) in HCV patients who reached sustained virological response (SVR)Imai et al. J Med Ultrason (2001). 2015 Jul;42(3):341-7.

• 42 HCV patients treated with interferon-based therapy, of which 6 presented with HCC during follow-up.

• SWE™ Protocol• Right liver via intercostal access

• Breath hold

• 3 measurements, with Q-Box™ of 10 mm in diameter

• EMean could predict the presence of HCC• AUROCs

− EMean: 0.963

− g-globulin: 0.888

− Age: 0.778

• Emean ≥ 6.5 kPa− Sensitivity: 83%

− Specificity: 83%


Conclusions

#1Liver Stiffness Measurement

•Technical Landscape

•Confounders

#2SWE™ Success Rate, Reliability and Reproducibility

•Healthy subjects

•Chronic hepatopathies

•Cirrhotic patients

•Protocol

#3Evaluation of Liver Fibrosis

•Stiffness of healthy liver

•Correlation of SWE with liver fibrosis

•Diagnostic performances

#4Prognostic Information

•Cirrhosis severity

•Portal hypertension

•Esophageal varices

#5Treatment Planning and Follow-up

•Liver transplantation

•Anti-viral treatments

•Monitoring of portal hypertension


Thank you for your attention.

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ShearWave™ Elastography in Chronic Liver Diseases: Clinical Research Literature Review