1. Non-Invasive Liver Testing

2. Non-invasive Liver Stiffness Testing
Assessing The Liver’s Mechanical Properties
Stiffness
Elasticity

3. FibroScan Operating Principle
Vibration Controlled Transient Elastography
VCTE™

4. VCTE Measurement Steps
Mechanically induce a shear wave
Measure shear wave speed
Calculate stiffness

5. Mechanical Shear Wave Induction5

6. Mechanical Shear Wave Induction
50 Hz Shear Wave 6

7. Shear Wave Speed Correlates to Stiffness
Low speed = Low Stiffness
High speed = High Stiffness

8. Shear Wave Speed Measurement
Pulse Echo Ultrasound
Ultrasound Pulse
Shear
Wave
Ultrasound Echo

9. Shear Wave Speed Measurement
Pulse Echo Ultrasound
Shear Wave Speed Measurement
Shear
Wave
Ultrasound Pulse
Ultrasound Echo

10. Mathematical Reconstruction of Shear Wave Propagation
25 mm
Time
65 mm
Propagation Map
Mathematical Reconstruction of Shear Wave Propagation
Subcutaneous Tissue
Liver
Tissue
Explored Region

11. Propagation Map Shear Wave Passes 25 mm Liver Tissue Time 25 mm 65 mm
Subcutaneous Tissue
Liver
Tissue
Shear Wave Passes 25 mm

12. Propagation Map Shear Wave Passes 65 mm Liver Tissue Time 25 mm 65 mm
Subcutaneous Tissue
Liver
Tissue
Shear Wave Passes 65 mm

13. Propagation Map Shear Wave Speed = D/T Liver Tissue Time 25 mm 65 mm
Subcutaneous Tissue
Liver
Tissue
Shear Wave Speed = D/T
40 mm
Time ?

14. Stiffness Calculation Formula
Measure
Calculate
Shear Wave Speed Vs (m/s)
Equivalent Stiffness E (kPa)
E = 3pVS2
Elasticity
(Stiffness)
Liver Tissue Density
Velocity of Shear Wave

15. Shear Wave Speed Examples
Slow
Fast
Depth
Depth
Time

16. Primary FibroScan Applications
Assess urgency of need for care
Guide DAA duration
Longitudinal testing
Disease progression
Disease progression rate
Therapeutic response

17. VCTE Cutoff Value References

18. Multiple Disease Groups
FibroScan Cutoff Value Reference
Multiple Disease Groups F3 F4
Disease
F0-F1 F2
Significant Fibrosis
Cirrhosis
HBV
< 6.0
> 6.0
> 9.0
> 12.0
HCV
< 7.0
> 7.0
> 9.5
HCV-HIV
< 10.0
> 11.0
> 14.0
Cholestatic
> 7.5
> 10.0
> 17.0
NAFLD/NASH
Utilization of FibroScan in Clinical Practice; Bonder et al, Current Gastroenterology Rep,

19. Multiple Disease Groups
FibroScan Cutoff Value Reference
Multiple Disease Groups F3 F4
Disease
F0-F1 F2
Significant Fibrosis
Cirrhosis
HBV
< 6.0
> 6.0
> 9.0
> 12.0
HCV
< 7.0
> 7.0
> 9.5
HCV-HIV
< 10.0
> 11.0
> 14.0
Cholestatic
> 7.5
> 10.0
> 17.0
NAFLD/NASH
Utilization of FibroScan in Clinical Practice; Bonder et al, Current Gastroenterology Rep,

20. VCTE Accuracy Validation Meta-Analysis
VCTE Versus Biopsy Staged Fibrosis
# Studies
# Patients
ETIOLOGY
Diagnosis of significant fibrosis
AUROC F≥F3
Diagnosis of cirrhosis
AUROC F4
REFERENCE 4
546
HCV
0.83
0.95
[1] 9
2083
Multiple
0.87
0.96
[2] 38
8433
0.84
0.94
[3]
Accuracy of FibroScan, Compared to Histology, in Analysis of Liver Fibrosis in Patients with HBV or HCV; A United States Multicenter Study; Clinical Gastroenterology & Hepatology 2015

21. VCTE Accuracy Validation Meta-Analysis
VCTE Versus Biopsy Staged Fibrosis
# Studies
# Patients
ETIOLOGY
Diagnosis of significant fibrosis
AUROC F≥F3
Diagnosis of cirrhosis
AUROC F4
REFERENCE 4
546
HCV
0.83
0.95
[1] 9
2083
Multiple
0.87
0.96
[2] 38
8433
0.84
0.94
[3]
Accuracy of FibroScan, Compared to Histology, in Analysis of Liver Fibrosis in Patients with HBV or HCV; A United States Multicenter Study; Clinical Gastroenterology & Hepatology 2015

22. Liver Stiffness Influencers
Fibrosis
Hepatic Blood Pressure 3
Hepatic Pressure
Alcohol 2
Hepatic Inflammation 1
Alanine aminotransferase-based Algorithms of Liver Stiffness Measurement by Transient Elastography (FibroScan) for Liver Fibrosis in Chronic Hepatitis B; Chan et al; Journal of Viral Hepatitis, 2009, 16, 36–44
Effect of Alcohol on Liver Stiffness Measured by Transient Elastography; Bardou-Jacquet et al; World Journal of Gastroenterology, Jan 28, 19(4);
Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension; Berzigotti, A., et al; PLOS One, 2013. 8(3): p. e58742

23. Meal Restriction Recommendation
Fast > 3 hours prior to testing
Drinking water is acceptable
Food intake increases liver stiffness in patients with chronic or resolved hepatitis C virus infection; Mederacke, I., et al; Liver International, 2009. 29(10): p
Liver Stiffness Is Influenced by a Standardized Meal in Patients With Chronic Hepatitis C Virus at Different Stages of Fibrotic Evolution; Arena et al; Hepatology, Volume 58, No 1, 2013

24. DAA Prequalification in HCV
27/04/2017
DAA Prequalification in HCV
Low
Significant Fibrosis
Cirrhosis
Stiffness
Low
Significant Fibrosis
Cirrhosis
Stiffness
Significant Fibrosis
Cirrhosis
Stiffness
DAA Qualified ?
Utilization of FibroScan Testing in Hepatitis C Virus Management; Gastroenterology & Hepatology Volume 11, Issue 3, March 2015
January 6, 2010

25. DAA Prequalification in HCV
27/04/2017
DAA Prequalification in HCV
Low
Significant Fibrosis
Cirrhosis
Stiffness
Low
Significant Fibrosis
Cirrhosis
Stiffness
Significant Fibrosis
Cirrhosis
Stiffness
DAA 12 Weeks
Utilization of FibroScan Testing in Hepatitis C Virus Management; Gastroenterology & Hepatology Volume 11, Issue 3, March 2015
January 6, 2010

26. DAA Prequalification in HCV
27/04/2017
DAA Prequalification in HCV
Low
Significant Fibrosis
Cirrhosis
Stiffness
Low
Significant Fibrosis
Cirrhosis
Stiffness
Significant Fibrosis
Stiffness
DAA 24 Weeks
Utilization of FibroScan Testing in Hepatitis C Virus Management; Gastroenterology & Hepatology Volume 11, Issue 3, March 2015
January 6, 2010

27. Practice Guideline Overview FibroScan VCTE Listings
Society
Region
Disease
Guidance
AASLD / IDSA1
USA
HCV
First line test
WHO2
World
HCV & HBV
EASL3
Europe
NICE4 UK
HBV
Recommendations for Testing, Managing and Treating Hepatitis C; When & In Whom to Initiate Antiviral Therapy, AASLD & IDSA Practice Guidelines;
2. WHO Guidelines for Screening, Care and Treatment of Persons with Hepatitis C Infection; ISBN
3. EASL Clinical Practice Guidelines : Noninvasive Tests for Evaluation of Liver Disease Severity and Prognosis; Journal of Hepatology 2015
4. Diagnosis and Management of Chronic Hepatitis B in Children, Young People & Adults; guidance.nice.org.uk/cg165

28. Report Review

30. FibroScan Operating Principle
Controlled Attenuation
Parameter
CAP™

31. Ultrasound Attenuation Rate
CAP Liver Assessment
Ultrasound Attenuation Rate
Unit: dB/M
(decibels per meter)

32. Ultrasound Attenuation Rate Example
Signal Intensity
75 %
50 %
25 %
0 %
50 mm
40 mm
30 mm
Depth Below Skin

33. Ultrasound Attenuation Normal Liver Tissue
Low Attenuation Rate

34. Ultrasound Attenuation Fatty Liver Tissue
High Attenuation Rate

35. Ultrasound Attenuation Rate Steatosis Correlate
Low attenuation rate = Low Steatosis
High attenuation rate = High Steatosis

36. CAP
Value
VCTE
Value

37. Echosens North America, Inc
Slide Deck Complements of:
Echosens North America, Inc
185 Alewife Brook Parkway
Suite 410
Cambridge MA 02138