approach to the cholestatic patient
TRANSCRIPT
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Approach to the cholestatic patient
Tom Hemming KarlsenOslo University Hospital, Norway
ASSA SAGES, August 8th, 2015
Best of EASL is a program supported by an unrestricted medical education grant by Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc.
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Karlsen et al., 2013
The cholestatic patient?
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Low quality prevalence data
Rogler et al. 2012
“The commonest indications for hepatic transplantation in adults included cryptogenic cirrhosis, auto-immune hepatitis and primary sclerosing cholangitis. In children biliary atresia was the commonest cause of liver failure.” (GrooteSchuur Hospital first 10 year report, 2000)
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Trauner et al., 1998
Defects of bile formation
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www.easl.eu
The EASL CPG summary
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The scientist approach
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Etiological considerations
Karlsen et al. 2015
Bull et al. 1998(PFIC1)
Strautnieks et al. 1998(PFIC2)
De Vree et al. 1998(PFIC3)
Sambrotta et al. 2014(PFIC4)
Paulusma et al. 1997(Dubin Johnson)
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Karlsen et al. 2015
Etiological considerations
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Liu et al. 2012, 2013DeBoer, 2014
Primary biliary cirrhosis
Primary sclerosing cholangitis
Autoimmune hepatitis
Etiological considerations
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Is genetics the right approach?
Franke et al. 2010Henriksen et al. 2014
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Drug induced liver injury (DILI)
https://www.genome.gov/26525384
Flucloxacillin
Lumiracoxib
Amoxicillin‐clavulunate
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Karlsen et al. 2015
Etiological considerations
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www.easl.eu
The clinician approach
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The clinician approach
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Karlsen et al. 2013
PSC and PBC
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Diagnosis of PBC (AASLD/EASL):
ALP ↑ AMA ↑ (90-95%) Biopsy (AMA negative patients, features of AIH)
“AMA negative PBC”: No genetic correlates (but underpowered) Slightly different cellular composition of histological lesions Other mitochondrial epitopes? Mostly similar clinical behavior and UDCA response Differential diagnosis: genetic cholangiopathies, SD-PSC
Approaching PBC
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Approaching PSC
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Diagnostic challenges in PSC
MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 – cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
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MRC vs. ERC
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T1 (and T2) algorithms and contrast-enhancement
Banjaree et al. 2014
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Diagnostic challenges in PSC
MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 – cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
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SSC vs. PSC
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Cholestasis in HIV
Sonderup et al., 2015
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Diagnostic challenges in PSC
MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 – cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
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IgG4 associated sclerosing cholangitis
Culver, courtesy sharingMendes et al., 2008
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IgG4 associated sclerosing cholangitis
Maillette de Buy Wenniger, 2012
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Diagnostic challenges in PSC
MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 – cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
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Overlap syndromes?
IAIHG position paper (2010): diagnose each entity, not «overlap» Features of AIH in PBC and PSC diagnosed by ALT/IgG/biopsy Controversy as to the utility of the IAIHG scoring system Treatment response for AIH features↓ - assessment/side effects
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Diagnostic challenges in PSC
MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 – cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
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Small-duct PSC
Karlsen et al. 2013 Naess et al. 2014
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Diagnostic challenges in PSC
MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 – cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
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The inflammatory bowel disease
Hirschfield et al. 2013Liu et al. in submission
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Sclerosing cholangitis in IBD
Mendes et al., 2006
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Diagnostic challenges in PSC
MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 – cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
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Malignancy surveillance in PSC
Cholangiocarcinoma (5-20%) – no validated screening protocol
Colorectal carcinoma (5x) – annual/biannual colonoscopy
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Malignancy surveillance in PSC
Cholangiocarcinoma (5-20%) – no validated screening protocol
Colorectal carcinoma (5x) – annual/biennial colonoscopy
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Malignancy surveillance in PSC
Cholangiocarcinoma (5-20%) – no validated screening protocol
Colorectal carcinoma (5x) – annual/biennial colonoscopy
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Karlsen et al., 2013
The cholestatic patient
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Summary points
Molecular and structural abnormities of heterogeneous etiologies Accounting for ~10% of European OLTs and common indication in SA Low threshold of MRC in IBD patients with abnormal hepatic biochemstries Molecular entities of inflammatory bowel diseases: UC, cCD, iCD, PSC-IBD «Overlap syndrome» should not be diagnosed, individual diseases should AMA-negative PBC and small-duct PSC without IBD: re-consider diagnosis The clinical utility of serum IgG4 remains challenging Further reading: www.easl.eu