From Binge Drinking to Alcoholic Liver Disease - Du Binge Drinking ...

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Journée d’Hépatologie du Centre Hépato-Biliaire – 13 juin 2014 - Paris
DDuu « bbiinnggee ddrriinnkkiinngg »
àà ll’’hhéép...

Alcohol-attributable deaths as a percentage of total
deaths

Important variations iinn lliivveerr cciirrrrhhoossiiss
mmoorrttaalliittyy aaccrroossss EEuurrooppee
HHiigghheerr rraatt...

Courtesy from D Leon. EASL 2010 Monothematic conference on ALD

Courtesy from D Leon. EASL 2010 Monothematic conference on ALD

COUNTRIES WWIITTHH IIMMPPRROOVVEEMMEENNTTSS
OOVVEERR PPAASSTT
1100--2200 YYEEAARRSS

Courtesy from D Leon. EASL 2010 Monothematic conference on ALD

AAllccoohhooll ccoonnssuummppttiioonn iinn EEuurrooppee

Cirrhosis in Europe: AA ppuubblliicc hheeaalltthh iissssuuee
Age-adjusted (world population) mortality rates from cirrhos...

COUNTRIES WWIITTHH IINNCCRREEAASSIINNGG
RRAATTEESS OOVVEERR PPAASSTT 1100--2200
YYEEAARRSS

Courtesy from D Leon. EASL 2010 Monothematic conference on ALD

Alcohol and mortality in Russia: prospective
observational study of 151 000 adults
David Zaridze, …. Peto R. Lancet 2014

Alcohol and mortality in Russia: prospective
observational study of 151 000 adults
David Zaridze, …. Peto R. Lancet 2014

TTHHEE EEMMEERRGGIINNGG IISSSSUUEESS::
BBiinnggee ddrriinnkkiinngg,, ““tthhee uunnsseettttlleedd
ddaaiillyy ddoossee oof...

Prevalence of NAFLD in EEuurroopp:: lleessssoonnss ffrroomm tthhee
DDiioonnyyssooss ssttuuddyy
PPrreevvaalleennccee ooff...

PPrrooggrreessssiioonn ooff oobbeessiittyy oovveerr tthhee ttiimmee
11999977 :: 88..22 %%
22000000 :: 99..66 %%
2200003...

Excess weight risk factor for
Alcoholic Liver Disease
60%
Overweight Patients
Non-Overweight Patients
35%
80%
70%
...

Effect of binge drinking on the liver:
An alarming public health issue?
• 3 questions on the potential impact of binge d...

Effect of binge drinking on the liver:
An alarming public health issue?
Binge drinking is a major public heath issue tha...

Effect of binge drinking on the liver:
An alarming public health issue?
Leon DL, Lancet 2006

Alcohol a major ppuubblliicc hheeaalltthh iissssuuee
TThhee bbiinnggee ddrriinnkkiinngg PPhheennoommeennoonn
11..22 bbii...

How to reduce the burden of
alchohol-attributable deaths:
The most efficient public
health policies

EASL call for EU action – on liver
disease
• Recognise alcohol consumption as one of the cross-cutting
risk factors for...

Public health policy need to use the
same concept than type II diabetes
 Primary prevention:
● For type II diabetes:
...

Disease progression non-iinnvvaassiivvee mmaarrkkeerrss iinn AALLDD
Fibrotest
< 0.32
0.32-0.58
>0.58
Naveau S, Hepato...

Alcoholic liver disease aanndd bbiioollooggiiccaall mmaarrkkeerrss
FFiibbrrootteesstt
Naveau S et al., Clin Gastroentero...

Le Dépistage améliore la survie
CHC sur VHC % des patients à
un stade précoce
Taux d’accès au
dépistage
Accès aux tra...

O’Shea RS, Hepatology 2010
Journal of Hepatology 2012
• First-line therapy in patients with severe ASH includes
cortico...

MMoovviinngg ttoowwaarrdd tthhee RReessppoonnssee
GGuuiiddeedd tthheerraappyy

LLiillllee mmooddeell:: aa ttooooll ffoorr nneeww ssttrraatteeggiieess
EEvvaalluuaattiioonn ooff LLiillllee mmooddeell oo...

Complete responders
Lille score ≤0.16 [≤35th percentile]
Partial responders
Lille score 0.16-0.56 [35-70th percentile] ...

• Current management
• Near Future
• Distant Future : Arbitrary selection of novel molecules
already tested in human be...

N-acetylcysteine aanndd ccoorrttiiccoosstteerrooiiddss ::
TThhee nneeaarr ffuuttuurree ??
NNAACC aalloonnee iiss iinneef...

Prednisolone With vvss WWiitthhoouutt PPeennttooxxiiffyylllliinnee
15.3%
Steroids + pentoxifylline
n=133
Steroids + Pl...

• Current management
• Near Future
• Distant Future : Arbitrary selection of novel
molecules already tested in human be...

PPootteennttiiaall tthheerraappeeuuttiicc ttaarrggeettss iinn tthhee ffuuttuurree
Unsuitable molecule
↓
RReeccoovveerry...

What can we learn from anti-TNF-a story
TNF-a and ALD
McClain CJ, Hepatology 1989
Kamimura Hepatology 1995
Yin M, Gast...

What can we learn from anti-TNF-a story?
Tilg H , J Hepatol 2003
Spahr L J hepatol 2002*
SSttuuddyy DDeessiiggnn
Mooke...

-
RReeccoovveerryy
↑↑ LLiivveerr FFuunnccttiioonn
DDiisseeaassee
↓↓ LLiivveerr FFuunnccttiioonn
Ideal molecule
IInnf...

Potential therapeutic ttaarrggeettss iinn tthhee ffuuttuurree
IL-1 receptor antagonist (IL-1Ra)
human IL-1ra [Anakinra®]...

Potential therapeutic ttaarrggeettss iinn tthhee ffuuttuurree
Interleukin 22 [F-652]
in phase I study
↓↓ AAllccoohhooll...

Potential therapeutic ttaarrggeettss iinn tthhee ffuuttuurree
Eculizumab [Soliris®]
Antibody against C5
↓↓ AAllccoohhoo...

• Current management
• Near Future
• Distant Future : Arbitrary selection of novel
molecules already tested in human be...

SSeevveerree AAllccoohhoolliicc HHeeppaattiittiiss
LLiivveerr TTrraannssppllaannttaattiioonn:: aa lloonngg wwaayy ttoo gg...

Where Do We Come From ?
SSEEVVEERREE AALLCCOOHHOOLLIICC HHEEPPAATTIITTIISS
LLIIVVEERR TTRRAANNSSPPLLAANNTTAATTIIOONN
Wh...

Early liver transplantation:
The French and Belgium Experience
Philippe Mathurin1, Christophe Moreno2, Didier Samuel3, J...

EEaarrllyy LLTT iinn AAllccoohhoolliicc hheeppaattiittiiss
• Early liver transplantation in non-responders undergoing
th...

Early LLTT iinn AAllccoohhoolliicc hheeppaattiittiiss
SSeelleeccttiioonn pprroocceessss== 44 TTeeaamm cciirrcclleess
Fam...

EEaarrllyy LLTT iinn AAllccoohhoolliicc hheeppaattiittiiss
Transplanted non responders N=26
Male gender no. [%] 15 [57.7...

Median [95%CI]
Lille score 0.88 [0.76 – 0.95]
MELD on first day of therapy 30.1 [27.7 - 33.4]
MELD day 7 28.5 [26.2 – 3...

Early Transplantation sshhiifftt ssuurrvviivvaall ooff
uunnrreessppoonnssiivvee ttoo rreessppoonnddeerrss
• Final combin...

EEaarrllyy LLTT iinn AAllccoohhoolliicc hheeppaattiittiiss

EEaarrllyy LLTT iinn AAllccoohhoolliicc hheeppaattiittiiss
• No alcohol relapse within the 6 month period
• 3 patients r...

Outcomes After Liver Transplantation for Alcoholic
Hepatitis Are Similar to Alcoholic Cirrhosis
Graft Survival Patient S...

1. In patients with severe ASH not responding to medical therapy,
early LT need to be further evaluated in carefully-sele...

PPHHRRCC QQuuiicckkTTrraannss--HHAAAA
AAHH nnoott rreessppoonnddiinngg ttoo mmeeddiiccaall tthheerraappyy
AAllggoorriitt...

• Current management
• Near Future
• Distant Future : Arbitrary selection of novel
molecules already tested in human be...

Better KKnnoowwlleeddggee ooff tthhee NNaattuurraall HHiissttoorryy
66 mmoonntthhss Deaths due to liver injury in > 90 % ...

UUnnmmeett nneeeeddss
• Animal models mimicking better liver Injury in human beings (liver
dysfunction and regeneration)...

NIAAA Announces Request for Applications oonn AAllccoohhoolliicc HHeeppaattiittiiss
“Integrated Approaches for Identifyin...

From Binge Drinking to Alcoholic Liver Disease - Du Binge Drinking à l'Hépatite Alcoolique

From Binge Drinking to Alcoholic Liver Disease - Du Binge Drinking à l'Hépatite Alcoolique

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