DIAGNÓSTICO NO INVASIVO DE CIRROSIS E HIPERTENSIÓN …

DIAGNÓSTICO NO INVASIVO

DE CIRROSIS

E HIPERTENSIÓN PORTAL

Salvador Augustin Hepatología-Medicina Interna

Hospital Vall d’Hebron, Barcelona

5º Curso de Residentes AEEH 30-31 Octubre 2015

• VHC

• ALT 70

• Plaq 145000

• Eco: bazo 12

BIOPSIA

GPVH

ENDOSCOPIA

Elastografía-cACLD

• Diabetes

• ALT 35, GGT 60

• Eco: esteatosis

• Control, dieta

Diagnóstico No Invasivo

Cirrosis / Hipertensión portal

i. Para qué el diagnóstico de cirrosis/HTP

ii. Diagnóstico NO invasivo HOY

iii. Hacia dónde vamos

Para qué el diagnóstico de

cirrosis/HTP

1. Cribado de complicaciones

• Varices

• HCC

2. Pronóstico

• Decisiones prácticas

• Estudios

3. Interpretar los síntomas y signos del paciente

Métodos Físicos

Métodos

Serológicos

Imagen

Datos clínicos

SIGNOS ROJOS EN V. ESOFAGICAS

ii. Cómo

ii. Cómo

Qué nospermiten HOY los métodos

diagnósticos no invasivos

1. Evitar exploraciones invasivas

– FGS (DESCARTAR varices)

– HVPG (ASUMIR CSPH)

2. Identificar precozmente cirrosis “oculta”

3. Estadiar al paciente (estudios)

ii. Cómo

¿A TODOS LOS PACIENTES CON CIRROSIS?

NO

Elastografía-cACLD


¿Cómo EVITAR endoscopia de cribado

VARICES?

- Métodos NO invasivos: DESCARTAR VNT

- Mejor COMBINACIONES de métodos: LSPS,

VRS, ANTICIPATE

- Riesgo aceptable : <5% VNT

N 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%

Elastografía-cACLD

¿Cómo EVITAR endoscopia de cribado

VARICES?

Fibroscan (LSM) + plaquetas

ANTICIPATE STUDY

N 23%

VNT 3.5%

N 34%

VNT 12%

N 57%

VNT 9%

N 43%

VNT 23%

N 12%

VNT 17%

N 31%

VNT 25%

379 patients with endoscopy

LSM ≥25 kPa LSM <25 kPa

Plat ≥ 150 000 Plat < 150 000 Plat ≥ 150 000 Plat < 150 000

393 patients with compensated cirrhosis

Abraldes et al., EASL 2015

ANTICIPATE STUDY

N 45%

VNT 5%

N 12%

VNT 24%

N 57%

VNT 9%

N 43%

VNT 23%

N 24%

VNT 17%

N 19%

VNT 29%

379 patients with endoscopy

LSM ≥25 kPa LSM <25 kPa

Plat ≥ 100 000 Plat < 100 000 Plat ≥ 100 000 Plat < 100 000

393 patients with compensated cirrhosis

Abraldes et al., EASL 2015

Baveno VI

SESSION 1 – Screening and surveillance ; invasive and non invasive methods

IDENTIFICATION OF PATIENTS WITH cACLD WHO 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 (3,B)

Patients with presumed/confirmed compensated cirrhosis

Routine blood tests (platelet count), abdominal ultrasound (US), liver stiffness (LS)

Non-Valid LS LS <25 kPa LS >=25

N=20 CSPH 16/20=80%

Normal

Plt+US

Low Plt

and/or Spleno

CSPH

3/5=60%

CSPH

13/15=87%

ASSUME CSPH

RULE 2: You can ASSUME CSPH in ALL patients with LS>=25 kPa (

in those with Non-Valid LS measurement and Platelet <

150000/mm3 & splenomegaly) (67 patients represent 67/182=37% of the studied population, if only patients with valid LS are considered; 67

15=82 patients,

who represent 82/202=41% of the studied population, including patients with non-valid LS;)

1CSPH: Clinically significant portal hypertension; *Low platelet count <150000/mm3; ¥ Splenomegaly is defined as spleen diameter >12 cm at abdominal ultrasound;

Fig. 5. ANTICIPATE : NON-INVASIVE ASSESSMENT OF CSPH

N=115 CSPH 45/115=39%

N=67 CSPH 64/67=96%

Normal

Plt+US

Low Plt

or

Spleno

Low Plt

and

Spleno

CSPH

5/34=16%

CSPH

13/35=37%

CSPH

27/46=59%

Fibroscan – CSPH en HCC

HCV All patients

Llop et al., J Hepatology 2012

Baveno VI

SESSION 1 – Screening and surveillance ; invasive and non invasive methods

DIAGNOSIS OF CSPH IN PATIENTS WITH cACLD

• 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 (3, B): – Liver stiffness by TE (≥20-25 kPa) alone or combined to Plt and

spleen size – Imaging showing collateral circulation

• The diagnostic value of TE for CSPH in other etiologies remains to be ascertained (5, D)

Elastografía-cACLD

Cirrosis oculta

Elastografía-cACLD

cACLD-LC

CLINICAL DIAGNOSIS

LIVER BIOPSY

TRANSIENT ELASTOGRAPHY

Cirrosis oculta – concepto cACLD

Elastografía-cACLD

Estudio N F/kPa %

Roulot, 2011 1190 ≥8

>13

7,5

0,76

Baba, 2011 423 ≥F2 14,3

Wong, 2012 922 ≥9,6 1,62

Fung, 2014 2493 ≥8,7

≥10,3

1,2

0,17

You, 2015 159 ≥F2

≥8

7

1,9

Koelher, 2015 3041 ≥8

≥13

5,6

0,6

Mayoría NAFLD

Cirrosis oculta – Población general

1% Población general LS>10

59% NAFL

7% NASH incompleto / fibrosis

leve 7% NASH fibrosis avanzada

73%

NAFLD

Kwok, et al. Gut 2015

NAFLD – DIABETES

(China)

CAP >222 dB/m

LS >9.5 kPa

Cirrosis oculta – Poblaciones de riesgo

Elastografía-cACLD

Estudio PRECISED

CONTROLES DIABÉTICOS

No Enfermedad Hepática aparente

Probable NASH / fibrosis leve

Probable NASH / Fibrosis avanzada

10-15% POBLACIÓN

DIABÉTICA TIENE

FIBROSIS

AVANZADA

NAFLD – DIABETES

(Barcelona) LS >10 kPa

Cirrosis oculta – Poblaciones de riesgo

Elastografía-cACLD

AMONG PATIENTS WITH UNSUSPECTED CIRRHOSIS:

Augustin, et al

Augustin, et al

Chen, et al

Chen, et al ANTICIPATE

*LSM≥13-13.6 kPa

* NO SIGNS OF CIRRHOSIS

AMONG PATIENTS WITH LSM≥13-13.6 kPa:

n=173

*8%

n=702

*14%

n=54 n=270 n=221

*24% *37% *15%

*10%

n=2876 Kim, et al

Cirrosis oculta – Población Hepatópatas

Elastografía-cACLD

Chen T, et al. Liver Int 2015

Cirrosis oculta – Peor Vigilancia

CLINICAL STAGE Adv.CHR. L.D. EARLY

COMPENSATED

CIRRHOSIS

LATE

COMPENSATED

CIRRHOSIS

DECOMPENSATED

CIRRHOSIS

LIVER

BIOLOGY

HISTOLOGY F3 F4 F4 F4

HVPG

(mmHg) <5 5 10

ELASTOGRAPH

Y (kPa) 8.5/

10 13,6 25

VARICES

SYMPTOMS ASYMPTOMATIC ASYMPTOMATIC ASYMPTOMATIC

(Varices)

HYPERDYNAMIC

CIRCULATION

DEFINING

FEATURE

Fibrosis,

Angiogenesis Scar, X-linking

Acellular scar,

nodules,

microthrombosis

Insoluble scar,

microthrombosis

LIVER

INFLAMMATION LIVER

SCAR 1) HVPG>10 = CSPH

2) HYPERDYNAM.

CLINICAL

DECOMPENSATION

CARCINOGENESI

S

• VHC

• ALT 70

• Plaq 145000

• Eco: bazo 12

<10-13

13-25

≥25

≥25 LTx

<25

Elastografía-cACLD

• Diabetes

• ALT 35, GGT 60

• Eco: esteatosis

• Control, dieta

Future research

CHALLENGES

STRATEGIES

1. Etiologies – reevaluate cut-offs

http://hepatitiscnewdrugresearch.com/

2. HCC – WHEN to start screening

Dyson, J Hepatol 2014; Wong, Hepatology 2014

1/3

Mittal, Clin Gastro Hepatol 2015

86%

72%

58%

0

10

20

30

40

50

60

70

80

90

100

Virus OH NAFLD

Cirrosis AP

N=1419 HCC

(VA – USA)

2. HCC – WHEN to start screening

Cost-effectiveness

Tsochatzis et al., NHS Health Tech Assess 2015 Armstrong et al., Q Med J 2013

How to do it

(combination of methods)

3. Detect Occult Cirrhosis

82-83% Prog. LENTOS (> 7 años)

Prog. RÁPIDOS (<6 años)

17%

18%

Singh et al., Clin Gastro Hepatol 2015; McPherson et al. J Hepatol 2015

4. Identify rapid progressors

Spleen stiffness:

• Basal: 37,4 kPa (17,3-75)

• 4 wk: 33,3 kPa (13,9-75)

• 12 wk: 31,9 kPa (11,8-75)

P = 0,09 P = 0,05

Elastografía-cACLD

Datos preliminares internos, sept. 2015

5. Response to therapies

HCV therapy – Changes in portal pressure

Towards hard outcomes

Vizzutti et al., Hepatology 2007 Robic et al., J Hepatology 2011

Physical Methods

Serologic Markers

Imaging

Clinical Data


Combining Methods

Take-Home Messages

• Evitar exploraciones invasivas

– FGS (DESCARTAR varices)

– HVPG (ASUMIR CSPH)

• Detección precoz cirrosis “oculta”

• Redefinición del concepto clínico de cirrosis

Impacto Métodos No Invasivos

CAPACIDAD PREDICTIVA

+ ¿ ?

Muchas Gracias

Q&A slides

i. Para qué

1. Cribado de complicaciones de la cirrosis

Varices HCC

i. Para qué 2. Pronóstico

Resección HCC

Bruix et al., Gastroenterology 1996

CSPH

5 mmHg

10 mmHg

i. Para qué

3. Estudios

HVPG ≥10

HVPG<10

Pacientes Outcomes

Ripoll et al., Gastroenterology 2007

Groszmann et al., NEJM 2005

i. Para qué

4. Interpretación de eventos clínicos del

paciente

“Complexity is

the enemy of

execution”

Development

of new

IDEAS

Development

of new

TOOLS

Development

of new

TOOLS

Development

of new

IDEAS

Development

of new

TOOLS

Non-Invasive Methods Hepatic venous pressure gradient (HVPG)

Development

of new

IDEAS

Etiologies – reevaluate cut-offs

What we talk about when we talk about cirrhosis

PROGNOSIS - RISKS

“Now there are many where before there was one…”

Robic et al. J Hepatol 2011

-100 Px -16 meses -65% CH -HVPG ≥10: 51% -Varices: 72% de CH -No tratamiento -41% alguna complicación

Elastografía-cACLD

Impacto elastografía-Pronóstico

G. García-Tsao, Hepatology 2010

DIAGNÓSTICO NO INVASIVO DE CIRROSIS E HIPERTENSIÓN …

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