Approach to the cholestatic patient
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1 Approach to the cholestatic patient Tom Hemming Karlsen Oslo 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.
2 The cholestatic patient? Karlsen et al., 2013
3 Low quality prevalence data 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. (Groote Schuur Hospital first 10 year report, 2000) Rogler et al. 2012
4 Defects of bile formation Trauner et al., 1998
5 The EASL CPG summary
6 The scientist approach
7 Etiological considerations Sambrotta et al (PFIC4) Bull et al (PFIC1) De Vree et al (PFIC3) Strautnieks et al (PFIC2) Paulusma et al (Dubin Johnson) Karlsen et al. 2015
8 Etiological considerations Karlsen et al. 2015
9 Etiological considerations Primary biliary cirrhosis Primary sclerosing cholangitis Autoimmune hepatitis Liu et al. 2012, 2013 DeBoer, 2014
10 Is genetics the right approach? Franke et al Henriksen et al. 2014
11 Drug induced liver injury (DILI) Flucloxacillin Lumiracoxib Amoxicillin clavulunate
12 Etiological considerations Karlsen et al. 2015
13 The clinician approach
14 The clinician approach
15 PSC and PBC Karlsen et al. 2013
16 Approaching PBC 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
17 Approaching PSC
18 Diagnostic challenges in PSC MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
19 MRC vs. ERC
20 T1 (and T2) algorithms and contrast-enhancement Banjaree et al. 2014
21 Diagnostic challenges in PSC MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
22 SSC vs. PSC
23 Cholestasis in HIV Sonderup et al., 2015
24 Diagnostic challenges in PSC MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
25 IgG4 associated sclerosing cholangitis Culver, courtesy sharing Mendes et al., 2008
26 IgG4 associated sclerosing cholangitis Maillette de Buy Wenniger, 2012
27 Diagnostic challenges in PSC MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
28 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
29 Diagnostic challenges in PSC MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
30 Small-duct PSC Karlsen et al Naess et al. 2014
31 Diagnostic challenges in PSC MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
32 The inflammatory bowel disease Hirschfield et al Liu et al. in submission
33 Sclerosing cholangitis in IBD Mendes et al., 2006
34 Diagnostic challenges in PSC MRC>ERC (AASLD/EASL) Secondary/etiologies? IgG4 cut-off level? Autoimmune hepatitis? Small-duct PSC? IBD? Malignancies?
35 Malignancy surveillance in PSC Cholangiocarcinoma (5-20%) no validated screening protocol Colorectal carcinoma (5x) annual/biannual colonoscopy
36 Malignancy surveillance in PSC Cholangiocarcinoma (5-20%) no validated screening protocol Colorectal carcinoma (5x) annual/biennial colonoscopy
37 Malignancy surveillance in PSC Cholangiocarcinoma (5-20%) no validated screening protocol Colorectal carcinoma (5x) annual/biennial colonoscopy
38 The cholestatic patient Karlsen et al., 2013
39 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:
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