Non-Invasive Liver Testing

Non-invasive Liver Stiffness Testing

Assessing The Liver’s Mechanical Properties

Stiffness Elasticity
 FibroScan Operating Principle

Vibration
Controlled
Transient
Elastography

VCTE ™
 VCTE Measurement Steps

• Mechanically induce a shear wave

• Measure shear wave speed

• Calculate stiffness
Mechanical Shear Wave Induction
Mechanical Shear Wave Induction

50 Hz Shear Wave
Shear Wave Speed Correlates to Stiffness

Low speed = Low Stiffness

High speed = High Stiffness

Shear Wave Speed Measurement
Ultrasound Echo

Shear
Wave

Ultrasound Pulse

Pulse Echo Ultrasound

Shear Wave Speed Measurement
Ultrasound Echo

Shear
Wave

Ultrasound Pulse

Pulse Echo Ultrasound

 Propagation Map
Mathematical Reconstruction of Shear Wave Propagation

Subcutaneous Tissue

25 mm

Explored
Liver Region
Tissue
65 mm

Time
 Propagation Map
Shear Wave Passes 25 mm
Subcutaneous Tissue

25 mm

Liver
Tissue
65 mm

Time
 Propagation Map
Shear Wave Passes 65 mm
Subcutaneous Tissue

25 mm

Liver
Tissue
65 mm

Time
 Propagation Map
Shear Wave Speed = D/T
Subcutaneous Tissue

25 mm

Liver 40 mm

Tissue
65 mm
Time ?

Time
Stiffness Calculation Formula
Measure Calculate
Shear Wave Speed Equivalent Stiffness
Vs (m/s) E (kPa)

E = 3pVS2
Elasticity Velocity of
(Stiffness) Shear Wave
Liver Tissue
Density
Shear Wave Speed Examples

D
e
p Slow
t
h

D
e
p
Fast
t
h

Time
15
 Primary FibroScan Applications
• Assess urgency of need for care

• Guide DAA duration

• Longitudinal testing
• Disease progression
• Disease progression rate
• Therapeutic response
 VCTE
Cutoff Value References
 FibroScan Cutoff Value Reference
Multiple Disease Groups
F3 F4

Disease F0-F1 F2 Significant Cirrhosis

Fibrosis
HBV < 6.0 > 6.0 > 9.0 > 12.0

HCV < 7.0 > 7.0 > 9.5 > 12.0

HCV-HIV < 7.0 < 10.0 > 11.0 > 14.0

Cholestatic < 7.0 > 7.5 > 10.0 > 17.0

NAFLD/NASH < 7.0 > 7.5 > 10.0 > 14.0

Utilization of FibroScan in Clinical Practice; Bonder et al, Current Gastroenterology Rep, 2014 16-372
 FibroScan Cutoff Value Reference
Multiple Disease Groups
F3 F4

Disease F0-F1 F2 Significant Cirrhosis

Fibrosis
HBV < 6.0 > 6.0 > 9.0 > 12.0

HCV < 7.0 > 7.0 > 9.5 > 12.0

HCV-HIV < 7.0 < 10.0 > 11.0 > 14.0

Cholestatic < 7.0 > 7.5 > 10.0 > 17.0

NAFLD/NASH < 7.0 > 7.5 > 10.0 > 14.0

Utilization of FibroScan in Clinical Practice; Bonder et al, Current Gastroenterology Rep, 2014 16-372
 VCTE Accuracy Validation
Meta-Analysis

VCTE Versus Biopsy Staged Fibrosis

Diagnosis of
Diagnosis of
# significant
# Patients ETIOLOGY cirrhosis REFERENCE
Studies fibrosis
AUROC F4
AUROC F≥F3

4 546 HCV 0.83 0.95 [1]

9 2083 Multiple 0.87 0.96 [2]

38 8433 Multiple 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
 VCTE Accuracy Validation
Meta-Analysis

VCTE Versus Biopsy Staged Fibrosis

Diagnosis of
Diagnosis of
# significant
# Patients ETIOLOGY cirrhosis REFERENCE
Studies fibrosis
AUROC F4
AUROC F≥F3

4 546 HCV 0.83 0.95 [1]

9 2083 Multiple 0.87 0.96 [2]

38 8433 Multiple 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
 Liver Stiffness Influencers
Liver Stiffness

Fibrosis
Hepatic Pressure

Hepatic Inflammation 1 Alcohol 2 Hepatic Blood Pressure 3

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

2. Effect of Alcohol on Liver Stiffness Measured by Transient Elastography; Bardou-Jacquet et al; World Journal of Gastroenterology, 2013 Jan 28, 19(4);
516-522

3. 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
 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. 1500-6.

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
 DAA Prequalification in HCV

Significant Fibrosis Significant Fibrosis

Cirrhosis Low Cirrhosis

Low

Stiffness Significant Fibrosis Stiffness

Cirrhosis

DAA Qualified ?
Stiffness

Utilization of FibroScan Testing in Hepatitis C Virus Management; Gastroenterology & Hepatology Volume 11, Issue 3, March 2015
 DAA Prequalification in HCV

Significant Fibrosis Significant Fibrosis

Cirrhosis Low Cirrhosis

Low

Stiffness Significant Fibrosis Stiffness

Cirrhosis

Stiffness

DAA 12 Weeks
Utilization of FibroScan Testing in Hepatitis C Virus Management; Gastroenterology & Hepatology Volume 11, Issue 3, March 2015
 DAA Prequalification in HCV

Significant Fibrosis Significant Fibrosis

Cirrhosis Low Cirrhosis

Low

Stiffness Significant Fibrosis Stiffness

DAA 24 Weeks
Stiffness

Utilization of FibroScan Testing in Hepatitis C Virus Management; Gastroenterology & Hepatology Volume 11, Issue 3, March 2015
 Practice Guideline Overview
FibroScan VCTE Listings

Society Region Disease Guidance

AASLD / IDSA1 USA HCV First line test

WHO2 World HCV & HBV First line test

EASL3 Europe HCV & HBV First line test

NICE4 UK HBV First line test

1. Recommendations for Testing, Managing and Treating Hepatitis C; When & In Whom to Initiate Antiviral Therapy, AASLD & IDSA
Practice Guidelines; www.hcvguidelines.org

2. WHO Guidelines for Screening, Care and Treatment of Persons with Hepatitis C Infection; ISBN 978 92 4 154875 5

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
Report Review
 FibroScan Operating Principle

Controlled
Attenuation
Parameter
CAP™
 CAP Liver Assessment

Ultrasound Attenuation Rate

Unit: dB/M
(decibels per meter)
Ultrasound Attenuation Rate Example
Signal Intensity 75 %
50 %
25 %
0%

50 mm
Depth Below Skin 30 mm 40 mm
Ultrasound Attenuation
Normal Liver Tissue

Low Attenuation Rate

Ultrasound Attenuation
Fatty Liver Tissue

High Attenuation Rate

 Ultrasound Attenuation Rate
Steatosis Correlate

Low attenuation rate = Low Steatosis

High attenuation rate = High Steatosis

 CAP VCTE
Value Value
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