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Dépistage du cancer du foie lors de cirrhose: utile?
Nicolas Goossens, MD, MSc, PD
Service de Gastroentérologie & Hépatologie
Journées Romandes d’Hépatologie
20 Juin 2019
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Maladies chroniques du foie
Hépatopathie
chronique avec
fibrose
10-50 ans
CirrhoseFoie normal
Carcinome
hépatocellulaire
Transplantation
Hépatite chronique - ~300 million au niveau mondial
CHC – tumeur avec incidence en croissance la plus
forte
Courtesy of S. Friedman (adapted)
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Data from GLOBOCAN 2012
Primary liver cancer incidence in 2012
0
5
10
15
20+
1-y incidence (per 100,000)
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Data from GLOBOCAN 2012
Primary liver cancer incidence in 2012
0
5
10
15
20+
1-y incidence (per 100,000)
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Increasing trend of HCC incidence & mortality
Altekruse et al, AJG 2014
HCC mortality
2000-10 (USA)
HCC annual incidence
2000-10 (USA)
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0.0
5.0
10.0
15.0
20.0
25.0
1989 1994 1999 2004 2009 2014
1-y
in
cid
en
ce
(p
er
10
0,0
00
)
Year
National Institute for Cancer Epidemiology and Registration (NICER).
www.nicer.org/
Increasing trend of HCC incidence(Switzerland)
M
F
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0.0
5.0
10.0
15.0
20.0
25.0
1989 1994 1999 2004 2009 2014
1-y
in
cid
en
ce
(p
er
10
0,0
00
)
Year
Increasing trend of HCC incidence(Switzerland)
M - Fr/Ital
F – Fr/Ital
M - Ger
F – Ger
National Institute for Cancer Epidemiology and Registration (NICER).
www.nicer.org/
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Dépistage du carcinome hépatocellulaire (CHC)?
WHO criteria for disease screening (excerpt)
the condition should be an important health
problem
there should be a recognisable latent or early
symptomatic stage
the natural history of the condition, including
development from latent to declared disease,
should be adequately understood
there should be an accepted treatment for
patients with recognised disease
there should be a suitable test or examination
that has a high level of accuracy
the test should be acceptable to the
population
Wilson, WHO, 1968
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HCC management overview
EASL, JHep 2012
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Dépistage du CHC: étude randomisée
Zhang et al, JCRCO, 2004
• 19’200 sujets HBV+
Chinois
• Randomisés dépistage
vs pas de dépistage
• Dépistage: AFP + US
tous les 6 mois
• Chez les sujets CHC
survie à 3 ans 53% vs 7%
p<0.01
Incidence CHC
Mortalité CHC
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Dépistage du CHC: étude randomisée?
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Improved survival of HCC if compliant with HCC surveillance
Lead-time adjusted survival in 216 patients with HCC and cirrhosis if compliant
or non-compliant to HCC surveillance guidelines
Costentin et al, Gastro, 2018
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HCC surveillance: meta-analysis
Early stage HCC
detection
(OR 2.08, 95% CI 1.80–2.37)
Curative treatment
rate
(OR 2.24 95% CI 1.99–2.52)
3-y survival
(OR 1.90 95% CI 1.67–2.17)
Singal et al, PLOS Med, 2014
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Recommandations pour le dépistage du carcinome hépatocellulaire
Société Qui dépister? Comment
dépister?
EASL 2018 • Cirrhose (Child A, B et Child C si
candidat pour TH)
• HBV: si non-cirrhotique à risque interméd-
haut
• F3: individualisé selon facteurs de risque
Echographie 1x / 6
mois
AASLD
2011 et
2018
• Cirrhose (Child A, B et Child C si
candidat pour TH)
• HBV: Selon origine ethnique, âge et
antécédents familiaux de CHC
• HCV F3 et NAFLD sans cirrhose le
bénéfice est incertain
US +/- AFP 1x / 6
mois
Seuil de coût-efficacité: incidence de CHC > 0.8-2.3% / année
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Limites aux strategies actuelles de dépistage du CHC
1. Mauvaise observance des recommandations
2. Changement d’étiologie du CHC
3. Performance hétérogène des outils de dépistage
4. Le futur…
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Limites aux strategies actuelles de dépistage du CHC
1. Mauvaise observance des recommandations
2. Changement d’étiologie du CHC
3. Performance hétérogène des outils de dépistage
4. Le futur…
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Poor adherence to HCC screening
Singal et al, J Gen Intern Med 2012
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Failure in HCC screening process in cirrhotic HCC patients
Singal et al, Cancer Prev Res, 2012
100%
80%
61%
24% 20%
5%
At-risk
Identify liver
disease
Recognize
cirrhosis
Order
surveillance
Surveillance
Consistent
Surveillance
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Limites aux strategies actuelles de dépistage du CHC
1. Mauvaise observance des recommandations
2. Changement d’étiologie du CHC
3. Performance hétérogène des outils de dépistage
4. Le futur…
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Pais et al, APT, 2017
Changing epidemiology of resected HCC etiology (Paris, France)
HCC etiology Proportion of F0-F2
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HCC etiology in the canton of Geneva 1990-2014, n=920
HBV9.1% NAFLD
8.3%
HCV20.7%
ALD43.2%
Other1.4%
Unknown17.3%
Travail de Master 2019 Shuna Myers, collaboration avec RGT,
Manuscrit en cours de publication
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Proportion of NAFLD-HCC by sex in the canton of Geneva
Travail de Master 2019 Shuna Myers, collaboration avec RGT,
Manuscrit en cours de publication
2%
5% 5%
10%12%
0%
6%
3%
15%
30%
0%
5%
10%
15%
20%
25%
30%
35%
1990-94 1995-99 2000-04 2005-09 2010-14
Pro
po
rtio
n o
f N
AF
LD
-HC
C
Years
Male NAFLD
Female NAFLD
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Limites aux strategies actuelles de dépistage du CHC
1. Mauvaise observance des recommandations
2. Changement d’étiologie du CHC
3. Performance hétérogène des outils de dépistage
4. Le futur…
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Simmons et al, APT, 2016
Performance of US for HCC screening in cirrhosis
Approx 20% of cirrhosis had
inadequate screening US
Associated with
-Male sex, Child-Pugh B or C
-BMI
-Etiology (Alcohol, NASH)
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Limites aux strategies actuelles de dépistage du CHC
1. Mauvaise observance des recommandations
2. Changement d’étiologie du CHC
3. Performance hétérogène des outils de dépistage
4. Le futur…
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Le futur: Adapter le dépistage au risque individel de CHC («médecine de précision»)
Fréquence Performance Coût
Stratification du
risque individual
par scores
cliniques ou
moléculaires
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Exemple 1: IRM + US chez les sujetsà très haut risque
Kim et al, JAMA Onc 2017
• Prospective study of 407
patients with cirrhosis (71%
HBV)
• Estimated risk HCC > 5% (modified Velazquez et al model: age, INR,
plt, HBV/HCV)
• Paired US and MRI
comparison
• HCC detected in 43 subjects
26%
86%
0%
20%
40%
60%
80%
100%
US MRI
Sensitivity for early HCC
(<5cm) detection
3-year survival
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Exemple 2: IRM abrégée, moinschère, plus rapide
Diffusion-weighted imaging (DWI) + T1-weighted imaging at the hepatobiliary
phase (T1w-HBP) post gadoxetic acid in 80 biopsy-proven HCC
Besa, Abdom Radiol 2017
Courtesy Bachir Taouli
Sensitivity: 81%
Specificity: 96%
Cost: 31%-49%
less then full
MRI
Arterial phase Portal phase
T1w-HBP DWI
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Exemple 3: AFP, utile chez certainspatients
Tzartzeva et al, Gastroenterology 2018
Gopal et al, CGH 2014
78%
45%
97%
63%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
All HCC Early HCC
US
US + AFP
Sensitivity of US or US +
AFP for HCC screening in
cirrhosis
7 studies (n=2770)18 studies (n=8526)
Improved diagnostic
performance of AFP in
non-HCV patients?
N=452 HCC / 676 non-HCC with cirrhosis
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Résumé des recommendations
Indication au dépistage du CHC:• Cirrhose Child-Pugh A ou B
• Cirrhose Child-Pugh C si projet de transplantation hépatique
• Hépatite B sans cirrhose selon score de risque
• Fibrose F3 selon risque individuel
Dépistage par US 2x/anPas de
nodule
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Résumé des recommendations
Indication au dépistage du CHC:• Cirrhose Child-Pugh A ou B
• Cirrhose Child-Pugh C si projet de transplantation hépatique
• Hépatite B sans cirrhose selon score de risque
• Fibrose F3 selon risque individuel
Dépistage par US 2x/an
Nodule identifié
Cirrhose et nodule < 1cm: Répéter US à 4 mois:
• Stable: suivi / 4 mois jusqu’à 1 an puis suivi standard / 6mois
• Nodule change/grandit: CT et/ou IRM et discuter à une réunion multidisciplinaire
Cirrhose et nodule >1cm: CT et/ou IRM:
• Discuter le patient à une réunion multidisciplinaire
Pas de cirrhose et nodule:
• En général le diagnostic de CHC nécessite une biopsie, adresser à une réunion
multidisciplinaire si besoin.
Pas de
nodule
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Merci pour votre attention