Dept. of Surgical, Oncologicaland Gastroenterological ... · PDF filecon colangite sclerosante...
26
Monotematica AISF Pisa, 18 ottobre 2013 Prototipi di pazienti con colangite sclerosante Prototipi di pazienti con colangite sclerosante Annarosa Floreani Dept. of Surgical, Oncological and Gastroenterological Sciences University of Padova La sottoscritta dichiara di non aver avuto negli ultimi 12 mesi conflitto d’interesse in relazione a questa presentazione e che la presentazione non contiene discussione di farmaci in studio o ad uso off-label
Transcript of Dept. of Surgical, Oncologicaland Gastroenterological ... · PDF filecon colangite sclerosante...
Monotematica AISF Pisa, 18 ottobre 2013
Prototipi di pazienti
con colangite
sclerosante
Prototipi di pazienti
con colangite
sclerosante
Annarosa FloreaniDept. of Surgical, Oncological and Gastroenterological
Sciences
University of Padova La sottoscritta dichiara di non aver avuto negli ultimi 12 mesi conflitto d’interesse in relazione a
questa presentazione e che la presentazione non contiene discussione di farmaci in studio o ad
uso off-label
Diagnosis of PSC
• A diagnosis of PSC is made in patients
with a cholestatic biochemical profile, whencholangiography ([MRC], [ERC], [PERC]) shows characteristic bile duct changes with multifocalstrictures and segmental dilatations, and secondarycauses of sclerosing cholangitis have beenexcluded.
• Patients who present with clinical, biochemicaland histological features compatible with PSC, but have a normal cholangiogram, are classified as small duct PSC.
AASLD PRACTICE GUIDELINESAASLD PRACTICE GUIDELINESAASLD PRACTICE GUIDELINESAASLD PRACTICE GUIDELINES
A diagnosis of PSC is made in patients with biochemical markers of cholestasis … when MRCP shows typical findings and causes of secondary sclerosing cholangitis are excluded.A liver biopsy is not essential for the diagnosis of PSC in these patients, but allows activity and staging of the disease to be assessed .
A liver biopsy should be performed to diagnose small duct PSC if high quality MRCP is normal. A liver biopsy may also be helpful in the presence of disproportionally elevated serum transaminases and/or serum IgG levels to identify additional or alternative processes.
ERCP can be considered if high quality MRCP is uncertain: the diagnosis of PSC is made in the case of typical ERCP findings in patients with IBD with normal high quality MRCP but high suspicion for PSC
PSC: Diagnostic prototypes
1. Classical PSC
2. PSC variants
Caveat: in any case do not forgot the colon!
PSC variants
� AIH~ 10% “AIH -like” adult PSC~ 25% “AIH -like” childhood PSC
� Small-duct PSC~ 10% of total PSC
- separate entity vs “early PSC”?
� IgG4 associated cholangitis (IAC)~ 10% of PSC patients (?)
- pancreatic involvement
Diagnosis of PSC/AIH overlap by use of the modified AIH score
Author Country N. of PSC pts
% with overlap
van Buuren, 2000 Netherlands 113 8%
Kaya M, 2000 USA 211 1.4%
Floreani, 20052010
Italy 4179
17%12.6%
Al-Chalaby, 2008 UK 211 6.1%
PSC: Quali sono le variabili che permettono di giungere alla caratterizzazione di profili diversi di malattia?
1. Eziopatogenesi
NO
2. Diagnostica: istologia? Genetica? Sierologia?
SI: ISTOLOGIA
PSC: Quali sono le variabili che permettono di giungere alla caratterizzazione di profili diversi di malattia?
Cholestatic biochemical profileCholestatic biochemical profileCholestatic biochemical profileCholestatic biochemical profile
Diagnosis (AASLD guidelines)
Liver biopsy for Liver biopsy for Liver biopsy for Liver biopsy for
diagnosis of Small diagnosis of Small diagnosis of Small diagnosis of Small
Duct PSCDuct PSCDuct PSCDuct PSC
No biliary dilation No biliary dilation No biliary dilation No biliary dilation at ultrasoundat ultrasoundat ultrasoundat ultrasound
Diagnostic Diagnostic Diagnostic Diagnostic of of of of
large duct large duct large duct large duct
PSCPSCPSCPSC
ERCPERCPERCPERCP
Non diagnosticNon diagnosticNon diagnosticNon diagnostic
MRCPMRCPMRCPMRCP
NormalNormalNormalNormal
NormalNormalNormalNormal Diagnostic Diagnostic Diagnostic Diagnostic of of of of
large duct large duct large duct large duct
PSCPSCPSCPSC
Istologia138CSP
30No Biopsia Epatica
108Biopsia Epatica
29Biopsia PRIMAdi Colangiografia
79Biopsia DOPOColangiografia
1Cambio
Management
OverlapAutoimmune
78Nessun cambioManagement
1complicanza1,3%1,3%
Burak et al. Am J Gastroenterol 2003
Liu JZ, Karslsen TH and the PSC Int Study
Group, Nat Genet 2013
0
1
2
3
4
5
6
7
8
ANA SMA
Pre-OLTx
Post-OLTx
Pre-OLTPost-OLT
PSC
ANA SMA
Autoantibody profile in PSC
Antibody Prevalence
Anti-BEC 63%
pANCA 26-94%
AMA 0-9%
LKM 0
Anti-SLA 0
ANA 8-77%
SMA 0-33%
ASCA 44%
Anti-cardiolipin 4-63%
AECA 35%
Anti-TPO 16%
Hov JR et al, WJG 2008
ANCA bile+ Anca bile - P
Dominant strictures 93% 63% 0.03
Amsterdam score 0.004
N. ERCs 0.01
ERC interventions 0.03
MELD score NS
CCA 1 3 NS
Death 3 2 NS
Transplantation 1 4 NS
PSC: ANCA in bile
Lenzen H et al, Scand J Gastroenterol 2013
3. Clinica
NO
PSC: Quali sono le variabili che permettono di giungere alla caratterizzazione di profili diversi di malattia?
PSC: Quali sono le variabili che permettono di giungere alla caratterizzazione di profili diversi di malattia?
Criteri per la diagnosi di IgG-4 sclerosing cholang itis
1. Aspetti colangiografici
2. IgG4 elevate
3. Coesistenza di malattia correlata a IgG-4 in altri organi
4. Caratteristiche isto-patologiche
Tanaka A J Autoimmunity 2013
4. Risposta al trattamento
?
PSC: Quali sono le variabili che permettono di giungere alla caratterizzazione di profili diversi di malattia?
PSC: Risposta al trattamento
VBMH FOCUS GROUPIndicator 1 – PSC
Efficacy of Treatment: ACUTE CHOLANGITIS
MEDIAN
RATING
(0-9)
DISAGREEMENT
INDEX (0-1)
Rate of acute cholangitis episodes needing antibiotic
treatment per PSC patient per year 9 0
Indicator 2 – PSC
Efficacy of Management: LTx
MEDIAN
RATING
(0-9)
DISAGREEMENT
INDEX (0-1)
Total number of pts <65 yrs old with PSC dead without
being listed for transplantation
DIVIDED
Total number of pts <65 yrs old with PSC not yet listed for
transplantation at study entry
9 0
Fabris L – AISF Single Topic Conference 2013
PSC: Risposta al trattamento
VBMH FOCUS GROUP
Fabris L – AISF Single Topic Conference 2013
Indicator 3 – PSC
Quality of Life (QoL)
MEDIAN
RATING
(0-9)
DISAGREEMENT
INDEX (0-1)
Total number of pts with PSC with improvementof QoL
after at least 1 yr
DIVIDED
Total number of pts with PSC with QoL data at study entry
and after at least 1 yr from study entry
8 0.15
Indicator 4 – PSC
Cancer-related Mortality
MEDIAN
RATING
(0-9)
DISAGREEMENT
INDEX (0-1)
Total number of pts with PSC dying for cancer (CCA and CRC)
DIVIDED
Total number of pts with PSC
9 0
Validation of a cholangiographic prognostic model
Ponsioen CY et al, Endoscopy 2010
Estimated transplantEstimated transplantEstimated transplantEstimated transplant----free survival can be appreciated by drawing a vertical line free survival can be appreciated by drawing a vertical line free survival can be appreciated by drawing a vertical line free survival can be appreciated by drawing a vertical line
from the total points SUMIHEHD scorefrom the total points SUMIHEHD scorefrom the total points SUMIHEHD scorefrom the total points SUMIHEHD score
Estimated transplantEstimated transplantEstimated transplantEstimated transplant----free survival can be appreciated by drawing a vertical line free survival can be appreciated by drawing a vertical line free survival can be appreciated by drawing a vertical line free survival can be appreciated by drawing a vertical line
from the total points SUMIHEHD scorefrom the total points SUMIHEHD scorefrom the total points SUMIHEHD scorefrom the total points SUMIHEHD score
Age
Points
Classification
Points
Total points
1-yrs survival
5-yr survival
10-yr survival
20 50 604030
C2
0 8
C3
15
C4
35 4025 30
47 29
200
70
98
94
5 10
96
89 82
90
72
15
6376859094
3.3132847
0.22.09.2
637684
244259
0 2 5 8 11 14
Pazienti con overlap: terapia immunosoppressiva
PSC: Quali sono le implicazioni dei profili di malattia n ella gestione del paziente?
UDCA 15-20 mg/Kg/day + prednisolone (with a tailored maintenance
dosage of 10-15 mg/day) + Azathioprine (50-75 mg/day)
300250200150100500
1,0
0,8
0,6
0,4
0,2
0,0
CUMULATIVE
SURVIVAL
FOLLOW-UP (months)
AIH/PSCPSC
• Global median survival 272.7 (CI 95%: 219.9-325.4)
• Cumulative probability of survival at 240 months: PSC 73.6%
AIH/PSC 87.5%
Antoniazzi, Floreani AISF 2010
Nishimori I , Otsuki M, Best Pract & Res Clin Gastroenterol 2009
PSC: Quali sono le implicazioni dei profili di malattia n ella gestione del paziente?
Pazienti con Pancreatite autoimmune: steroidi
Broomè 1996
Asymptomatic better prognosis
Tishendorf 2007
PSC: Quali sono le implicazioni dei profili di malattia n ella gestione del paziente?
Bjornsson et al, Gut 2002Bjornsson et al, Gut 2002Bjornsson et al, Gut 2002Bjornsson et al, Gut 2002
N=33 vs n=260 with large N=33 vs n=260 with large N=33 vs n=260 with large N=33 vs n=260 with large
duct PSC [Oxford and Oslo] duct PSC [Oxford and Oslo] duct PSC [Oxford and Oslo] duct PSC [Oxford and Oslo]
Median followMedian followMedian followMedian follow----up: 106 vs up: 106 vs up: 106 vs up: 106 vs
105 months105 months105 months105 months
Bjornsson et al, Bjornsson et al, Bjornsson et al, Bjornsson et al, Gastroenterology 2008 Gastroenterology 2008 Gastroenterology 2008 Gastroenterology 2008
N=83 vs n=166 with large N=83 vs n=166 with large N=83 vs n=166 with large N=83 vs n=166 with large
duct PSC [Europe and USA] duct PSC [Europe and USA] duct PSC [Europe and USA] duct PSC [Europe and USA]
Median followMedian followMedian followMedian follow----up: 11 yrsup: 11 yrsup: 11 yrsup: 11 yrs
PSC: Quali sono le implicazioni dei profili di malattia n ella gestione del paziente?
Small duct PSC
Low dose UDCA* vs mod dose UDCA** Survival free of liver tranplantation
*Lindor et al, NEJM 1997 **Olsson J Hepatol 2004
Death/Tranplantation:7.2% UDCA vs 10.9% placebo (ns)
High dose UDCA trial
*Lindor et al, 2009
Outcomes variables in PSC challenges
� Undefined basis of disease heterogeneity� Unpredictable events (Cholangiocarcinoma)� Management of IBD, pauchitis and colorectal cancer�Lack of efficient therapy�MELD vs dysplasia/pruritus/fatigue/recurrent cholangitis
