Madrid, 21 Febrero 2018

43 Congreso Anual AEEH

Curso de Postgrado

Salvador Augustin

Medicina Interna - Hepatología

Hospital Universitari Vall d’Hebron

Universitat Autònoma de Barcelona

ENFERMEDAD HEPÁTICA CRÓNICA AVANZADA

(cACLD) Concepto y potenciales ventajas sobre el concepto

de cirrosis

Clinical case

- 55 yo female

- Sent for incidental steatosis at abdominal US

- History: hypertension (losartan 50 mg/d)

- Physical Exam: height 1.54, weight 86 kg (BMI 36.2)

- Blood: AST 34, ALT 24, GGT 129, plat 200.000, Glu 112,

TC 161, TGC 206

- No alcohol, virus -, ANA -, Ferritin 230

Clinical case

-LS 12.3 kPa, IQR 1.0

-CAP 391, IQR 42

-SR 10/11

• Cirrhosis– Importance

– Limitations

• Impact of Fibroscan

• cACLD– Definition

– Association to histology and clinical outcomes

Outline

• PROGNOSIS

– Prophylaxis of variceal bleeding

– Screening HCC

• STUDIES / TRIALS (design, interpretation)

– Diagnostic / prognostic

– Therapeutic

Diagnosis of Cirrhosis – What For?

What patients are at risk of complications?

To this aim, is the concept of cirrhosis useful?

• Invasive

• Sample variability

• Inter-observer variability

• Poor sensitivity for staging

within cirrhosis

Histologic diagnosis of cirrhosis - LIMITATIONS

García-Tsao et al., Hepatology 2010

More than one “cirrhosis”…

Liver (spleen) stiffness

Serumbiomarkers

Imaging

Clinical signs

SIGNOS ROJOS EN V. ESOFAGICAS

Non-invasive diagnosis of cirrhosis

Development of new TOOLS Development of new IDEAS

EV  53%,  CSPH  77%  EV  63%,  CSPH  65%  

“Classic” diagnosis of cirrhosis

NORMAL Plt & US ABNORMAL Plt &/or US

N=250 Patients with compensated chronic liver disease

<13.6 kPa >13.6 kPa <13.6 kPa >13.6 kPa

N=290 General Liver ClinicsN=40 Known

CSPH/decomp.

Routine blood tests, abdominal US, LS measurement

Follow-Up Upper Endoscopy + HVPG

2/3 1/3

EV 20%, CSPH 65%

NORMAL Plt & US ABNORMAL Plt &/or US

N=40

N=182 Patients with presumed/confirmed compensated cirrhosis

<13.6 kPa

CSPH9/20=45%

>13.6 kPa

CSPH1/20=5%

N=142

<13.6 kPa

CSPH 90/119=75%

>13.6 kPa

CSPH9/23=39%

132

9

19

LSM <8 kPa LSM 8-10 kPa LSM ≥10 kPa

(82%)

453

LSM <8 kPa LSM 8-10 kPa LSM ≥10 kPa

(94%)

(12%)

(6%) (6%)

Diabetics N=160 Controls N=48

LS>10 kPa: 19/160 (12%)

PRECISED studyAsymptomatic Diabetic Population (Barcelona)

1 HCV+ (LSM 75 kPa)2 OH (LSM 18,8 i 45 kPa)1 HBsAg+ (LSM 10,3 kPa)15 OCCULT NASH: 53% NORMAL ALT & PLAT

?

CLINICAL DIAGNOSI

S

CLINICAL DIAGNOSI

S

TRANSIENTELASTOGRAPH

Y

F0 F1 F2 cACLD-LC

CLINICAL DIAGNOSI

S

LIVER BIOPSY

TRANSIENTELASTOGRAPH

Y

CHRONIC LIVER DISEASE

Impact of elastography - cACLD

Baveno 6 – Defining cACLD

• TE values <10 kPa in the absence of other known clinical signs rule out cACLD

•Values between 10-15 kPa are suggestive of cACLD but need further test for

confirmation

•Values >15 kPa are highly suggestive of cACLD

de Franchis et al., J Hepatol 2015

Tsochatzis, et al. EASL ILC 2017

cACLD - Histology

Stage HCV(n=2609)

NAFLD(n=889)

HBV(n=695)

Total(n=4198)

0 171 (7%) 177 (20%) 83 (12%) 431 (10%)

1 796 (30%) 276 (31%) 246 (35%) 1318 (31%)

2 866 (33%) 192 (22%) 168 (24%) 1226 (29%)

3 431 (17%) 144 (16%) 114 (16%) 689 (16%)

4 345 (13%) 100 (11%) 84 (12%) 529 (13%)

cACLD 1218 (29%)

Meta-analysis individual patients, 8 European centres

Tsochatzis, et al. EASL ILC 2017

F0-F2 cACLD Se Sp PPV NPV LR (+) LR (-)

TE <10 KPa 2587 365 86.8 69.9 68.5 87.6 2.9 0.19

TE >15 KPa 95 485 39.8 96.8 83.6 79.7 12.5 0.6

cACLD - HistologyMeta-analysis individual patients, 8 European centres

• Between 10-15 kPa suggestive of cACLD

• >15 kPa highly suggestive of cACLD

ANTICIPATE STUDY

229 patientsLSM/HVPG

48LS 10-15

181LS ≥15

HVPG>5 mmHg85.5%

CSPH: 29%

HVPG>5 mmHg95.5%

CSPH: 75%

cACLD - Portal Hypertension

Chen T, et al. Liver Int 2015

N=685 (HCV 31%, HBV 25%, NALD 22%, ALD 4%)

cACLD - Outcomes: Decompensation

Park, et al. Expert Rev Gastro Hep 2014

Meta-analysis, N=5085 (mixed etiologies, HBV >60%)

cACLD - Outcomes: risk of HCC

Tatsumi, et al. Hepatol Res 2015

N=1002 (HCV 72%, HBV 10%, Other 18%)

cACLD - Outcomes: risk of HCC

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)

20-30 (25)

VARICES

10

HVPG (mmHg) 5 10

HCC

>10

Liver Bx: NASH, NAS 7, F4 HVPG: 6 mmHg

LS 12.3 kPa

Gracias!!!