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Institute for Liver and Digestive Health
Use of Elastography in Portal Hypertension
Dr. Davide Roccarina Specialist in General Medicine Specialist Doctor in Clinical Ultrasound and non-invasive liver assessment Hepatology Department Division of Medicine Royal Free Hospital
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1. Pre-hepatic pre-sinusoidal
2. Intra-hepatic pre-sinusoidal
3. Intra-hepatic sinusoidal
4. Intra-hepatic post-sinusoidal
5. Post-hepatic post-sinusoidal
Cirrhosis
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?
“Decompensating
Event” Stage 3
Bleeding
Stage 4 First non
bleeding
decompensation
Stage 5
Second
decompensation
Death or
OLT
SEPSIS
Renal
Failure
Decompensated Cirrhosis
Stage 1
No Varices
No Ascites
Varices
No Ascites
Stage 2 Years
Months
Compensated Cirrhosis
Portal Hypertension
Cirrhosis
Liver Cirrhosis: natural history
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Portal Hypertension: pathogenesis
OHM’S LAW
ΔP = Q × R
Dynamic Component
Static Component
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OLTx DEATH
SBP
ASCITES
ESOPHAGEAL VARICES
RAPTURE
BLEEDING
HEPATO-RENAL SYNDROME
CSPH is an independent predictor of clinical decompensation
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HVPG
Upper GI endoscopy
Portal Hypertension: reference standard
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Procopet B and Berzigotti A, Gastroenterology Report, Volume 5, Issue 2, 1 May 2017,
Portal Hypertension: non-invasive techniques
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Procopet B and Berzigotti A, Gastroenterology Report, Volume 5, Issue 2, 1 May 2017,
Liver Transient Elastography/Fibroscan
Portal Hypertension: non-invasive techniques
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Liver Transient Elastography for detection of CSPH
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Detection of CSPH: pre-Baveno VI
Auguatin, Journal of Hepatology 2014
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Journal of Hepatology 2015
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Detection of CSPH: Baveno VI Identification of Low Risk Patients not Immediately Requiring
Endoscopic Surveillance
Journal of Hepatology 2015
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Study N Viral
%
ALD
%
Varices VNT Varices
missed
VNT
missed
OGD
spared
OGD
unneeded
Perazzo 97 - - 54% - 6% 0 22% 29%
Tossetti 146 100 - 45% 8% 6% 0 27% 34%
Chang* 173 55 - 31% 8% - 1.7% 20% -
Thabut* 790 100 - - - 10% 0 20% -
Paternostro* 135 47 30 65% 24% 3% 0 7% 30%
Silva* 112 80 7 48% 15% 1.8% 0 11% 43%
Cales* 287 26 64 44% 17% 2% 0 16.5% 41.5%
Ahmed* 478 33 36 - 11% - 0.5% 23% -
Maurice 310 55 13 23% 5% 3.5% 0.6% 33% 48%
TOTAL 2528 12% 0.3% 20% 38%
Perazzo, J Hepatol 2015; Tossetti, DLD 2016; *EASL 2016; Maurice, J Hepatol 2016
Validation of Baveno VI Criteria for Avoiding Screening Endoscopy
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N=499
Spared endoscopies
VNT missed
Platelets >150 + LSM <20 kPa
(Baveno VI) 68 (14%) 2/68 (3%) (0.8-10%)§
Platelets >110 + LSM <25 kPa (Expanded-Baveno VI) 158 (32%) 3/158 (1.9%) (0.6-5.4%)
Study cohort Spared endoscopies VNT missed/
Expanded-Baveno VI* VNT missed/
All patients§
Anticipate 158/499 (32%) 3/158 (1.9%) (0.6-5.4%)¥ 3/499 (0.6%) (0.1-1.9%)
London 161/309 (52%) 3/161 (1.9%) (0.6-5.3%) 3/309 (1%) (0.3-2.8%)
Vall d’Hebron 48/117 (41%) 0/48 (0%) (0.7-9.2%) 0/117 (0%) (0-3.1%)
All cohorts 367/925 (40%) 6/367 (1.6%) (0.7-3.5%) 6/925 (0.6%) (0.3-1.4%)
Augustin, Hepatology 2017
Expanded Baveno VI Criteria are Safe and Effective
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LS≥21.1 kPa
AUROC 0.845
(0.767-0.923)
HVPG≥10 mmHg
AUROC 0.830
(0.751-0.910)
Prognostic Capacity of Liver Stiffness Values
Risk of Decompensation
Robic, Journal of Hepatology 2011
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Prognostic Capacity of Liver Stiffness Values
Risk of Death
Verniol, Gastroenterology 2011
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Procopet B and Berzigotti A, Gastroenterology Report, Volume 5, Issue 2, 1 May 2017,
Liver
Portal Hypertension: non-invasive techniques
Spleen Elastography
Transient Elastography/Fibroscan
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1. – Sufficient intercostal space width
2. - Splenic parenchymal thickness > 4 cm (by US)
3. – Success rate > 60% and IQR < 30% of median value 4. – Intra-observer reproducibility 96%, inter-observer
reproducibility 94%
5. – Probe upper limit 75 kPa
Measurement of Spleen Stiffness by Liver Transient Elastography/Fibroscan
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P = 0.0000
R2 = 0,78
5
10
15
20
25
30
35
0
20 30 70 80 40 50 60
Spleen Stiffness (kPa)
P = 0.0000
R² = 0,70
0
5
10
15
20
25
30
35
10 20 50 60 70 30 40
Liver Stiffness (kPa)
HVPG
(m
m H
g)
Esophageal Varices: NO Esophageal Varices: YES
Colecchia A. et al., Gastroenterology 2012 ; 143(3):646-54
Cirrhosis
HVPG
(m
m H
g)
Compensated Cirrhosis
Spleen Stiffness vs. Liver Stiffness for the detection of Esophageal Varices
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EV: YES EV: NO EV: YES EV: NO
Colecchia A. et al., Gastroenterology 2012 ; 143(3):646-54
Spleen Stiffness vs. Liver Stiffness for the detection of Esophageal Varices
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Colecchia, Journal of Hepatology 2014
Prognostic Value of Spleen Stiffness in Cirrhosis
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• 260 patients: with Chronic Liver Disease due to HCV, HBV or Alcoholic Liver Disease were
prospectively enrolled.
An upper GI-endoscopy for EV grading, liver (LSM) and spleen (SSM) stiffness measurements performed within 6 months.
SSM measured according to 2 parameters :
1) standard FS technical settings used for LSM: SSM-50Hz
2) new settings specifically dedicated to the spleen: SSM-100Hz
Only cases with at least 8 valid SSM-100Hz were kept in the analysis.
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SSM-50Hz SSM-100Hz
SSM-50Hz vs SSM-100Hz
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SSM-100Hz HVPG
SSM-100 Hz vs HVPG
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TARGET SSM-100 Hz HVPG P value
AUC 0,835 (0,757-
0,913) 0,749 (0,643-
0,854) <0,001
SSM-100 Hz vs HVPG
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216 patients
Baveno VI criteria : LSM < 20 kPa and platelet count > 150 x 109 cells/L (De Franchis J Hepatol 2015)
• SSM-100Hz cut-off value of 38.3 kPa was calculated in the population excluding Baveno VI criteria (n = 193) with a sensitivity of 95 %.
Expanded-Baveno VI criteria : LSM < 25 kPa and platelet count > 110 x 109 cells/L (Augustin & Pons Hepatology 2017)
• SSM-100Hz cut-off value of 38.3 kPa was calculated in the population excluding Expanded-Baveno VI criteria (n = 154) with a sensitivity of 95 %.
(*) McNemar test (**) ² test
Baveno VI Baveno VI + SSM p
Missed HREV / number of HREV (*) 1 / 51 (2 %) 3 / 51 (5.9 %) 0.48
Missed HREV / number of spared endoscopy (**) 1 / 22 (4.5 %) 3 / 69 (4.3 %) 1
Missed HREV / all patients (*) 1 / 216 (0.5 %) 3 / 216 (1.4 %) 0.48
Spared endoscopy (*) 22 / 216 (10.2 %) 69 / 216 (31.9 %) <0.001
Expanded-Baveno VI Expanded-Baveno VI + SSM p
Missed HREV / number of HREV (*) 7 / 51 (13.7 %) 9 / 51 (17.6 %) 0.48
Missed HREV / number of spared endoscopy (**) 7 / 55 (12.7 %) 9 / 83 (10.8 %) 0.947
Missed HREV / all patients (*) 7 / 216 (3.2 %) 9 / 216 (4.2 %) 0.48
Spared endoscopy (*) 55 / 216 (25.5 %) 83 / 216 (38.4 %) <0.001
Baveno ± SSM -100 Hz
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Procopet B and Berzigotti A, Gastroenterology Report, Volume 5, Issue 2, 1 May 2017,
Liver
Portal Hypertension: non-invasive techniques
Spleen Elastography
Shear Wave Elastography
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ARFI (Siemens) ElastPQ (Philips) Epiq, Supersonic
Point Shear Wave Elastography
2D Shear Wave Elastography
RT-SWE
Newer US Elastography: Visual Control of Stiffness Measurement
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EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY, 2018
Liver stiffness Reference standard: HVPG
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EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY, 2018
Spleen stiffness Reference standard: HVPG
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Spleen stiffness Reference standard: Upper GI
EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY, 2018
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ARFI (Siemens) ElastPQ (Philips) Epiq, Supersonic
Point Shear Wave Elastography
2D Shear Wave Elastography
RT-SWE
Newer US Elastography: Visual Control of Stiffness Measurement
Few studies although results are promising!!!
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0
10
20
30
40
50
60
70
80
noPH NCSPH SPH CSPH
HVPG
Sple
en
-SW
E
0
5
10
15
20
25
30
35
40
45
50
noPH NCSPH SPH CSPH
HVPG
Live
r-SW
E
P<0.0001 P<0.0001
78 patients with CLD admitted for HVPG measurement were recruited into the study
Our preliminary data…
Matteo Rosselli et all, Royal Free Hospital, London
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0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
4.00
4.50
5.00
HVPG noPH NCSPH CSPH SPH
LSP
S
P<0.0001
Non invasive assessment of CSPH LSPS = LS * (spleen length/Plt count)
Our preliminary data…
Matteo Rosselli et all, Royal Free Hospital, London
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0
20
40
60
80
100
120
noPH NCSPH CSPH SPH
SSP
SA
HVPG
P<0.0001
Our preliminary data… Non invasive assessment of CSPH
SSPSA = SS * (spleen area/Plt count)
Matteo Rosselli et all, Royal Free Hospital, London
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SSWE 0.918 LSWE 0.895 LSPS 0.911 SSPSA 0.895
AUROC for CSPH (HVPG>10 mmHg)
Our preliminary data…
Matteo Rosselli et all, Royal Free Hospital, London
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AUROC for SPH (HVPG>12 mmHg)
SSWE 0.922 LSWE 0.869 LSPS 0.899 SSPSA 0.869
Our preliminary data…
Matteo Rosselli et all, Royal Free Hospital, London
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LSWE PORTAL PRESSURE HVPG 6-9 HVPG 10-11 HVPG ≥12
AUC 95% CI 0.918 (0.851-0.986) 0.895 (0.820-0.970) 0.869 (0.785-0.952)
Cut-off (kPa) 11.8 18.6 19.9 Sensitivity (%) 82 85 87 Specificity (%) 91 84 83
PPV (%) 81.6 84.6 89 NPV (%) 91 84.1 83
SSWE PORTAL PRESSURE HVPG 6-9 HVPG 10-11 HVPG ≥12
AUC 95% CI 0.898 (0.825-0.971) 0.918 (0.853-0.983) 0.922 (0.861-0.983)
Cut-off (kPa) 30.2 42.7 50 Sensitivity (%) 84 96 87 Specificity (%) 86 84 83
PPV (%) 83.7 78.1 89 NPV (%) 85.7 97.4 83
Our preliminary data…
Matteo Rosselli et all, Royal Free Hospital, London
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Our preliminary data…PSC
Davide Roccarina et all, Royal Free Hospital, London
P<0,0001
P<0,0001
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Our preliminary data…PSC
Davide Roccarina et all, Royal Free Hospital, London
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Combination of Liver and Spleen Stiffness
Berzigotti A, J Hepatol 2017
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CPH NCPH p value
LSWE (kPa) 24 5.8 <0.0001
SSWE (kPa) 55.6 93.3 <0.0001
SA (cm2) 72.4 116 <0.009
Platelets/mm3 124 180 <0.001
SS/LS (kPa) 2.3 14.2 <0.0001
0
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NCPH CPH
Live
r-p
SWE
P<0.0001
0
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NCPH CPH
Sple
en
-pSW
E P<0.0001
Our preliminary data…
Matteo Rosselli et all, Royal Free Hospital, London
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LIVER SPLEEN
LIVER
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LIVER stiffness SPLEEN stiffness
NON-CIRRHOTIC PH
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THANK YOU