gianni testino sc patologia delle dipendenze ed epatologia ... · necro –inflammatory activity...
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Gianni Testino
SC Patologia delle Dipendenze ed Epatologia
Centro Alcologico Regionale Ligure
ASL3 Liguria c/o Osp. Policlinico San Martino, Genova
Società Italiana di Alcologia
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Buscarini et al, White paper of Italian Gastroenterology; Dig Liver Dis 2014
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Associazione Italiana Studio Fegato, 2007
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Associazione Italiana Studio Fegato, 2007
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Associazione Italiana Studio Fegato, 2007
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Di Pascoli M et al, Dig Dis 2016
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HOST
✓ BMI – Visceral obesity
✓ Hyperlipidemia
✓ Type 2 Diabetes
✓ Insulin Resistence
✓ Metabolic syndrome
“Endogenous Ethanol”
Peroxisome Mitochondria ER
(AOX) (MRC) (CYP 2E1,
CYP 4A10,
CYP 4R14)
STEATOSIS
Necro – Inflammatory
Activity
Genotype 3
Insulin
Leptin
Resistin
PIA I- 1
ENDOTOXIN
Others ECM- Producing Cells
FIBROSIS
STELLATE CELLS
MYOFIBROBLAST LIKE PHENOTYPE
LIPID PEROXIDATION
(HNE - MDA)
REACTIVE OXYGEN SPECIES
(O•, O2•, OH•,H2O2)
(Core protein/NS5A)
IMPAIRMENT OF
RESPIRATORY
CHIAN
Inflammatory –Cytochines
(> TNF a, > IL8, TGF b1, PDGF,….)
Genotype non 3
HCV
(Cell Death)
OXIDATIVE STRESS
✓ ATP and NAD depletion
✓ DNA and protein damage
✓ Glutathione depletion
Y-Glu-Cys-Gly
(KC activation)
SH
ALCOHOL
HEPATOCYTE INJURY
ACETALDEHYDE
Aldehyde-protein-adducts
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Fibrosi sinusoidale e pericellulare in steatoepatite tipo ASH.
Freccia indica i corpi di Mallory
F. Grillo, Anatomia Patologica, Università di Genova
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Shah et al, Clin Gastroenterol Hepatol, 2019
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Shah et al, Clin Gastroenterol Hepatol, 2019
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DELAYED DIAGNOSIS OF HCC WITH ALCOHOLIC LIVER DISEASE
43.7%
Schutte et al, Liver Cancer 2012
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SC Patologia delle Dipendenze ed Epatologia
Centro Alcologico Regionale Ligure, ASL3 c/o Ospedale Policlinico San Martino, Genova
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Application of hepatocellular carcinoma surveillance in a European
setting. What can we learn from clinical practice ?
In a European setting, only 22% of HCCs were diagnosed by surveillance, and
in more than one-third of cases, surveillance was indicated but missed.
NAFLD and alcoholic liver disease were associated with deficient surveillance.
Survival was significantly better in patients who underwent surveillance compared
with those in whom surveillance was missed although indicated.
Edenvik P et al, Liver Int 2015
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motivation
hepato-alcohologist
Modified, from Singal et al; ACG Clinical Guideline: Alcoholic Liver disease 2018
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Testino and Pellicano 2018, in press
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Moreno et al; J Hepatol 2019, 70:273 kPa
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Loomba et al, Gastroenterology 2015; 149: 278-81
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NORMAL LIVER
FATTY LIVER
ALCOHOLIC
HEPATITISCIRRHOSIS*
60 – 100 %
20-40 %
40 %HCC
Compensated: Abstainer 90%,
Continue to drink < 70%
* 5 years survival
Scompensated: Abstainer 50%,
Continue to drink < 30%
8-20%
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Adebayo D et al, Clin Liver Dis 2019
PAMPs: pathogen associated molecular pattern
EABV: effective arterial blood volume
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Adebayo D et al, Clin Liver Dis 2019
HVPG: hepatic venous pressure gradient
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Di Pascoli M et al, Dig Dis 2016
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Classification of HE
Montagnese S, Ponziani FR et al, AISF guidelines - DLD 2018
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427 admission
64.4% alcoholic liver disease (ALD)
13.6% ALD/HCV/HBV
58.5% readmission (median time 58 days)
31.2% (30-day)
Hepatic Encephalopathy : 41%
Active drinkers 43.8%
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Patologia Alcol Correlata
-intossicazione
-s. astinenza
Cirrosi Epatica
Patologia Psichiatrica
sintomatologia
psichiatrica
euforia
tremori
insonnia
allucinazioni
convulsioni
ecc
tremori
agitazione psico-motoria
ecc
confusione
amnesia
coma
ENCEFALOPATIA EPATICA IN PAZIENTE CON DISTURBO DA USO DI ALCOL
P Balbinot, Genova 4 Aprile 2019
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Balbinot P, Testino G, Leone S, Caputo F; Digestive and Liver Disease; Letter to the Editor, in press
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I BISOGNI DEL FAMIGLIARE (CAREGIVER INFORMALE)
Spesso il CI può sentirsi inadeguato e sopraffatto da una situazione
complicata;
Talvolta sente la mancanza di un adeguato supporto da parte degli
altri membri familiari;
può percepire l’assistito come manipolazione, ingratitudine e irragionevolezza;
da ciò ne può derivare «burnout» psico-fisico
Il caregiver formale dovrà decifrare per tempo i primi sintomi di
questa condizione per intervenire tempestivamente evitando danni
all’integrità psico-fisica del CI e possibili ripercussioni negative
sul paziente (incuria, violenza verbale, ecc)
relazione d’aiuto
invio supporto psicologicoP Balbinot, Genova 4 Aprile 2019
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Colangite Biliare Primitiva (CBP)
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Williams et al, The Lancet, Vol 391 March 17, 2018
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Ferrarese et al, World J Hepatol 2018; doi: 10.378/wjg.v24.i38.4403
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Cirrosi Epatica Alcol Correlata e Trapianto: Sopravvivenza
Europe:
84% at 1 year; 78% at 3 years; 73% at 5 years
Burra et al, Am J Transplant 2010
USA:
92% at 1 year; 86% at 3 years; 86% at 5 years
Japan:
81.3% at 1 year; 78.5% at 3 years; 75.7% at 5 years
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PAZIENTE
AssociazioniAuto-mutuo-Aiuto
FAMIGLIACaregiver Inf.
OPERATORI -SANITARI
-SOCIO- SANITARI
Caregiver formali
GESTIONE CIRROSI EPATICA
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GRAZIE…….