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¿Qué utilidad tienen los métodos elastográficosen el paciente con enfermedad hepática avanzada? EHCAc/cACLD
Joan Genescà
Hospital Universitari Vall d’Hebron, VHIR, UAB, CIBERehd, Barcelona
CURSO DE POSTGRADO41 CONGRESO ANUAL AEEH
THE FRENCH CHEESESCAN CONECTION
IT'S UN BRIE LIEVA BLE;;[euro] 95,000 cheese scanner can spot liver disease as well.
Les quatre fondateurs d’Echosens® dans les locaux de l’Ecole Supérieure de Physique et de Chimie Industrielles (ESPCI) : de gauche à droite :Jean-Michel Hasquenoph, Bertrand Fourquet, Laurent Sandrin, Sylvain Yon
PhD1998-2000
Echosens2001
Artículo científicoModelo comercial
2003
Esquema
•Situación pre-‐elastografía•Impacto elastografía cACLD
•Cambio epidemiológico• Prevalencia EHC poblacional• Prevalencia cACLD en EHC
•Concepto cACLD: Compensated advancedchronic liver disease (fibrosis grave +cirrosis compensada)•Pronóstico/seguimiento/manejo•Varices/CSPH y elastografía
Situación pre-elastografía
• Datos clínicos (analíticos, imagen)• PBH• Al descompensarse• No se diagnosticaba
Sospecha/diagnóstico cACLD/cirrosis
Elastografía-cACLDSituación pre-elastografía
• Joven• ALT 45• VHB• Eco normal• Control
Elastografía-cACLDSituación pre-elastografía
• Adulto DBT• ALT 35• GGT 60• Eco esteatosis• Control, peso
1500 VA HCC patients1201 (80%) cirrhosis
HCV 72%
905 (75%)known cirrhosis
81% HCCBCLC B-‐D
61% HCC surveillance
296 (25%)unknown cirrhosis
97% HCCBCLC B-‐D
18% HCCsurveillance
Walker, et al. Aliment Pharmacol Ther 2016
Situación pre-elastografía-HCC cribado
Elastografía-cACLDImpacto elastografía-Epidemiología
F0/1 F2 F3 ACLD-LC
CLINICAL DIAGNOSIS
LIVER BIOPSY
TRANSIENTELASTOGRAPHY
Elastografía-cACLDImpacto elastografía-Población general
Estudio N F/kPa %
Roulot, 2011 1190 ≥8>13
7,50,76
Baba, 2011 423 ≥F2 14,3
Wong, 2012 922 ≥9,6 1,62
Fung, 2014 2493 ≥8,7≥10,3
1,20,17
You, 2015 159 ≥F2≥8
71,9
Koelher, 2015 3041 ≥8≥13
5,60,6
Mayoría NAFLD
Elastografía-cACLDImpacto elastografía-Población de riesgo
PRECISED• 124 pacientes (105 diabéticos /19 controles)
Diabéticosn = 105
Controles n = 19 P
Elastografía (kPa) 5,6 (2,7) 4 (2,5) 0,002
• Pacientes con LSM ≥10 kPa:
– 0 controles (0%)
Elasticidad ≥10 kPaDiabéticos
n = 13 (12,4%)
Mediana (kPa) 16,5
Mínimo (kPa) 10,3
Máximo (kPa) 75
IQR (kPa) 6,9
Datos internos, Servicio Hepatología-HUVH, feb. 2016
Impacto elastografía-EHC
CHRONIC LIVER DISEASE WITH NO SIGNS OF LIVER CIRRHOSIS
Augustin, et al
Augustin, et al
Chen, et al
Chen, et al ANTICIPATE
A.
B.
*Patients with LSM≥13-13.6 kPa
*Patients with occult ACLD (no signs of liver cirrhosis) PATIENTSWITH LSM≥13-13.6 kPa
n=173*8%
n=702*14%
n=54 n=270 n=221
*24% *37% *15%
*10%n=2876Kim, et al
Elastografía-cACLDImpacto elastografía-EHC
Chen T, et al. Liver Int 2015
Efectos de tests no invasivos (TE) en EHC
-Situación clínica nueva en EHC
-Más pacientes detectados en fases tempranas de cirrosis/cACLD
-No todos son cirróticos
-Recomendaciones de cribaje
Elastografía-cACLDImpacto elastografía-cACLD
¿PORQUÉ cACLD?
-Enmarcar una situación clínica
-Seleccionar pacientes para estudios clínicos y terapeúticos
-Proporcionar recomendaciones de cribaje
cACLD: compensated advanced chronic liver disease
Impacto-elastografía-cACLD
1) Cirrosis es un diagnóstico histológico
2) No siempre hay cirrosis en los pacientes clasificados como F4 por tests no invasivos
3) No hay consenso sobre una definición clínica de cirrosis
4) Pacientes en estadios pre-‐cirróticos pueden tener hipertensión portal
5) Cribaje de HCC puede estar indicada en estadios pre-‐cirróticos
6) Los tests no invasivos han cambiado el escenario clínico de la EHC
¿PORQUÉ cACLD Y NO CIRROSIS?
Impacto elastografía-cACLD
• TE permite identificación en fases tempranas de pacientes con EHC en riesgo de desarrollar CSPH• Término refleja que el espectro de fibrosis grave y cirrosis es un continuo clinicamente indistinguible• cACLD y cirrosis compensada: términos aceptados• Pacientes con sospecha de cACLD: remitir a hepatólogo• TE es suficiente para sospechar cACLD:
•<10 kPa descarta cACLD•Entre 10-‐15 kPa sugiere cACLD+ confirmación•>15 kPa diagnóstico de cACLD
• TE útil para identificar CSPH y descartar varices
cACLD-concepto-Baveno VI-2015
F3 F4 F4
CLINICAL STAGE
COMPENSATED CIRRHOSIS
DECOMPENSATED CIRRHOSIS
CLD
HISTOLOGY
CLINICAL STAGE
ELASTOGRAPHY (kPa)
DECOMPENSATED CIRRHOSIS
cACLD
10+ 15
Impacto elastografía-cACLD
Robic, et al. J Hepatol 2011
-100 Px-16 meses-65% CH-HVPG ≥10: 51%-Varices: 72% de CH-No tratamiento-41% alguna complicación
Impacto elastografía-Pronóstico
Impacto elastografía-Seguimiento
94 pacientes con cACLD (seguimiento: 43 meses)
Datos internos, Servicio Hepatología-HUVH, feb. 2016
<21 kPa ≥21 kPa
2/57(3.5%)
95% CI: 0-8.3%
12/37(32.4%)
95%CI: 17.3-47.5%
Baseline LSM
<10% ≥10%
4/58(6.9%)
95% CI: 0.4-13.4%
10/33(30.3%)
95% CI: 14.6-46%
Delta LSM
Impacto elastografía-Seguimiento
Datos internos, Servicio Hepatología-HUVH, feb. 2016
<21 kPa ≥21 kPa
2/57(3.5%)
95% CI: 0-8.3%
12/37(32.4%)
95% CI: 17.3-47.5%
Baseline LSM
Delta LSM
<10% ≥10% <10% ≥10%
Delta LSM
0/38(0%)
95% CI: 0-0%
2/16(12.5%)
95% CI: 0-28.7%
4/20(20%)
95% CI: 2.5-37.5%
8/17(47.1%)
95% CI: 23.3-70.8%
Elastografía hepática:• Basal: 20,8 kPa (11,1-‐75)• 4 sem.: 17,5 kPa (7,8-‐48)• 12 sem.: 18,3 kPa (7,8-‐61,5)
P = 0,002P = 0,014
Impacto elastografía-Seguimiento tratamiento
41 pacientes cACLD95% genotipo112 sem. Simeprevir+sofosbuvir+riba
Datos internos, Servicio Hepatología-HUVH, feb. 2016
Elastografía-cACLD
• Elasticidad esplénica: congestión: presión portal
Impacto elastografía-Seguimiento tratamiento
Elastografía esplénica: • Basal: 45,7 kPa (17,3-‐75)• 4 sem.: 34,8 kPa (13,9-‐75)• 12 sem.: 32,1 kPa (12,3-‐75)
P = 0,175P = 0,037
Impacto elastografía-Seguimiento
Datos internos, Servicio Hepatología-HUVH, feb. 2016
Elastografía-cACLDImpacto elastografía-Epidemiología
F0/1 F2 F3 ACLD-LC
CLINICAL DIAGNOSIS
LIVER BIOPSY
TRANSIENTELASTOGRAPHY
96
40
20
40
60
80
100
%
Yes No
11
89
0
20
40
60
80
100
%
Yes No
Q 2 Do you perform screening EGD in patients with ACCLD at the time of diagnosis to detect the presence of gastro esophageal varices ? 48 answers
Q3 If your answer was YES do you use non-invasive methods to restrict the performance of EGD to the patients at higher risk of having varices ? 48 answers
cACLD-varices
Panelistas Baveno VI-2015
¿ENDOSCOPIA A TODOS LOS PACIENTES cACLD?
NO
cACLD-varices
Augustin S, et al. J Hepatol 2013
cACLD-varices
¿Qué pacientes con cACLD pueden evitarla endoscopia de cribado?
cACLD-varices
-‐TE es mejor para descartar (rule out) varices ( Se/NPV)
-‐Rendimientomejora combinandoparametros clínicos:
LSPS, VRS, ANTICIPATE
-‐Reglas de clasificación simples y visuales funcionanmejor
-‐Riesgo aceptable de varices no sospechadas: <5% VNT
Baveno VISESSION 1 – Screening and surveillance ;; invasive and non invasive methods
CONSENSUS STATEMENTS
IDENTIFICATION OF PATIENTS WITH cACLDWHO CAN SAFELY AVOID SCREENING ENDOSCOPY
• Patients with a liver stiffness < 20 kPa and with a platelet count > 150,000 have a very low risk of having varices requiring treatment, and can avoid screening endoscopy (1b;A)
• These patients can be followed up by yearly repetition of TE and platelet count (5;D)
• If liver stiffness increases or platelet count declines, these patients should undergo screening EGD (5;D)
No. All
varices
VNT Classification rule All varices
NPV
VNT
NPV
Varices
missed
VNT
missed
Endoscopies
avoided
Augustin, et al 49 10% 0 LSM<25
LSM<25+Pla≥150
93%
100%
100%
100%
7%
0
0
0
61%
20%
Montes, et al 85 45%* 20% LSM<20
LSM<20 and/or Pla>120
90%
100%
-‐
100%
9.5%
0
-‐
0
25%
15%
Ding, et al 271 -‐ 10% LSM<25+Pla≥100 -‐ 100% -‐ 0 39%
ANTICIPATE 379 42% 15% LSM<25+Pla≥100
LSM<25+Pla≥150
79%
86%
95%
96.5%
21%
14%
5%
3.5%
45%
23%
Descartar varices en cACLDcACLD-varices
ANTICIPATE STUDY
Assessing noninvasive tools to identify cirrhotic portal hypertensionand true risk of esophageal varices
-Juan Abraldes, Michael Ney;; Edmonton, Canada-Annalisa Berzigotti, Jaime Bosch;; Barcelona, Spain-Cristophe Bureau;; Toulouse, France-Horia Stefanescu, Bodgan Procopet;; Cluj-Napoca, Romania-Salvador Augustin, Joan Genescà;; Barcelona, Spain
No publicado
cACLD-varices
ANTICIPATE STUDY
N = 86 (23%)EV = 12 (14%)VNT = 3 (3.5%)
N = 129 (34%)EV = 44 (34%)VNT = 16 (12%)
N =215 (57%)EV = 56 (26%)VNT = 19 (9%)
N =164 (43%)EV = 104 (63%)VNT = 37 (23%)
N = 46 (12%)EV = 22 (48%)VNT = 8 (17%)
N = 118 (31%)EV = 82 (69%)VNT = 29 (25%)
379 patients with endoscopy
LSM ≥25 kPaLSM <25 kPa
Plat ≥ 150 000 Plat < 150 000 Plat ≥ 150 000 Plat < 150 000
393 patients with compensated cirrhosis
cACLD-varices
¿Qué pacientes se pueden clasificarcomo pacientes con CSPH?
-‐TE mejor para asegurar (rule in) CSPH ( Es/PPV)
-‐Rendimientomejora poco combinando paramétros cínicos:
LSPS, PHRS, ANTICIPATE
-‐Reglas de clasificación simples y visuales funcionanmejor
-‐PPV de CSPH: 90%
cACLD-CSPH
Baveno VISESSION 1 – Screening and surveillance ;; invasive and non invasive methods
CONSENSUS STATEMENTS
DIAGNOSIS OF CSPH IN PATIENTS WITH cACLD• HVPG measurement is the gold-‐standard method to assess the presence of clinically significant portal hypertension, which is defined as HVPG≥10 mmHg (1b;A)
• By definition, patients without CSPH have no gastroesophageal varices, and have a low 5-‐yr risk of developing them (1b;A)
• In patients with virus related cACLD non-‐invasive methods are sufficient to rule-‐in CSPH, defining the group of patients at risk of having endoscopic signs of PH. The following can be used (2b; B):
Baveno VISESSION 1 – Screening and surveillance ;; invasive and non invasive methods
CONSENSUS STATEMENTS
DIAGNOSIS OF CSPH IN PATIENTS WITH cACLD (II)• Liver stiffness by TE (≥20-‐25 kPa; at least two measurements on different days in fasting condition; caution should be paid to flares of ALT; refer to EASL guidelines for correct interpretation criteria), alone or combined to Plt and spleen size
• The diagnostic value of TE for CSPH in other etiologies remains to be ascertained (5;D)
• Imaging showing collateral circulation is sufficient to rule-‐in CSPH in patients with cACLD of all etiologies (2b;B)
N = 46 (25%)CSPH = 8 (17%)
N = 69 (38%)CSPH = 37 (54%)
N =115 (63%)CSPH = 45 (39%)
N =67 (37%)CSPH = 64 (96%)
N = 17 (9%)CSPH = 16 (94%)
N = 50 (28%)CSPH = 48 (96%)
393 patients with compensated cirrhosis
LSM ≥25 kPaLSM <25 kPa
Plat ≥ 150 000 Plat < 150 000 Plat ≥ 150 000 Plat < 150 000
182 HVPGCSPH 109 (60%)
ANTICIPATE STUDYcACLD-CSPH
N = 46 (25%)CSPH = 8 (17%)
N = 69 (38%)CSPH = 37 (54%)
N =115 (63%)CSPH = 45 (39%)
N =67 (37%)CSPH = 64 (96%)
393 patients with compensated cirrhosis
LSM ≥25 kPaLSM <25 kPa
Plat ≥ 150 000 Plat < 150 000
182 HVPGCSPH 109 (60%)
ANTICIPATE STUDYcACLD-CSPH
105
HVPG (mmHg)
ELASTOGRAPHY (PPV)
20kPa: 85-‐90%
25kPa: 95%
30kPa: 100%
cACLD-CSPH
RESUMEN
-‐Los tests no invasivos (TE) tienen un gran impacto en el manejo de la EHC
-‐El nuevo concepto de cACLD será útil para la práctica clínica y la investigación
-‐El cribado de varices puede evitarse en un grupo substancial de pacientes con cACLD
mediante reglas de clasificación simples utilizando TE y recuento de plaquetas
-‐Mediante la elastografía se puden seleccionar pacientes con CSPH
-‐Otros pruebas no invasivas similares a la TE probablemente sean igualmente útiles
Resumen
F3 F4
CLINICAL STAGE
EARLY COMPENSATED
CIRRHOSIS
DECOMPENSATED CIRRHOSIS
CLD
HISTOLOGY F4 F4
LATE COMPENSATED
CIRRHOSIS
CLINICAL STAGE
DECOMPENSATED CIRRHOSIS
EARLY cACLD
LATEcACLD
ELASTOGRAPHY (kPa)
10+ 15
20-‐30 (25)
VARICES
HVPG (mmHg)
5 10
GRACIAS
Baveno VISESSION 1 – Screening and surveillance ;; invasive and non invasive methods
CONSENSUS STATEMENTS
DEFINITION OF COMPENSATED ADVANCED CHRONIC LIVER DISEASE (cACLD)
• The introduction of transient elastography in clinical practice has allowed the early identification of patients with chronic liver disease (CLD) at risk of developing clinically significant portal hypertension (CSPH) (1b;A).
• For these patients, the alternative term “compensated advanced chronic liver disease (cACLD)” has been proposed to better reflect that the spectrum of severe fibrosis and cirrhosis is a continuum in asymptomatic patients, and that distinguishing between the two is often not possible on clinical grounds. (5; D)
DEFINITION OF COMPENSATED ADVANCED CHRONIC LIVER DISEASE (cACLD) (II)
• Currently, both terms : “cACLD” and “compensated cirrhosis” are acceptable. (5; D)
• Patients with suspicion of cACLD should be referred to a liver disease specialist for confirmation, follow-‐up and treatment (5;D)
Baveno VISESSION 1 – Screening and surveillance ;; invasive and non invasive methods
CONSENSUS STATEMENTS
Baveno VISESSION 1 – Screening and surveillance ;; invasive and non invasive methods
CONSENSUS STATEMENTS
CRITERIA TO SUSPECT cACLD• Liver stiffness by transient elastography is sufficient to suspect cACLD in asymptomatic subjects with known causes of CLD (1b;A)
• Transient elastography often has false positive results; hence 2 measurements on different days are recommended in fasting conditions (5;D)
• TE values < 10 kPa in the absence of other known clinical signs rule-‐out cACLD; values between 10 and 15 kPa are suggestive of cACLD but need further test for confirmation; values > 15 kPa are highly suggestive of cACLD (1b;A)
Baveno VISESSION 1 – Screening and surveillance ;; invasive and non invasive methods
CONSENSUS STATEMENTS
CRITERIA TO CONFIRM cACLD• Invasive methods are employed in referral centers in a stepwise approach when the diagnosis is in doubt or as confirmatory tests
• Methods and findings that confirm the diagnosis of cACLDare :– Liver biopsy showing severe fibrosis or established cirrhosis (1a;A); collagen proportionate area (CPA) measurement on histology provides quantitative data on the amount of fibrosis and holds prognostic value (2b;B) and its assessment is recommended (5;D)
– Upper GI endoscopy showing gastroesophageal varices (1b;A)– Hepatic venous pressure gradient (HVPG) measurement; values > 5 mmHg indicate sinusoidal portal hypertension (1b;A)
Criterios de validación/utilización dereglas clasificación exclusión de varices
cACLD-varices
-‐Pacientes con cACLD detectados por elastografía
-‐Diseño secuencial y prospectivo
-‐Evaluación por etiologías
-‐Exclusión pacientes con riesgo elevado de varices:
-‐Descompensados
-‐Child B-‐C
-‐Circulación colateralevidente en imagen
-‐Varices conocidas
HCVAll patients
Impacto elastografía-Pronóstico
Llop, et al. J Hepatol 2012
393 patients with compensated cirrhosis
N = 170 (45%)EV = 36 (21%)VNT = 8 (5%)
N = 45 (12%)EV = 20 (44%)VNT = 11 (24%)
N =215 (57%)EV = 56 (26%)VNT = 19 (9%)
N =164 (43%)EV = 104 (63%)VNT = 37 (23%)
N = 92 (24%)EV = 48 (52%)VNT = 16 (17%)
N = 72 (19%)EV = 56 (78%)VNT = 21 (29%)
379 patients with endoscopy
LSM ≥25 kPaLSM <25 kPa
Plat ≥ 100 000 Plat < 100 000 Plat ≥ 100 000 Plat < 100 000
ANTICIPATE STUDY
cACLD-varices
N = 46 (25%)CSPH = 8 (17%)
N = 69 (38%)CSPH = 37 (54%)
N =115 (63%)CSPH = 45 (39%)
N =67 (37%)CSPH = 64 (96%)
393 patients with compensated cirrhosis
LSM ≥25 kPaLSM <25 kPa
Plat ≥ 150 000 Plat < 150 000
182 HVPGCSPH 109 (60%)
ANTICIPATE STUDYcACLD-CSPH