¿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