Primary Sclerosing Cholangitis. Bibleclass Felix Brunner
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1 Primary Sclerosing Cholangitis Bibleclass Felix Brunner
2 Overview Epidemiology Pathogenesis Clinical Features, Genetics, Immunology Diagnosing PSC Treatment Medications, Transplantation Cancer-Risk & Surveillance Biliary & Colorectal Cancers Bibleclass , Brunner 2
3 Epidemiology Geographic Distribution North South Gradient Northern Europe most frequent Incidence: 1.3 per inhabitants Prevalence: 16.3 per inhabitants Gender & Age Distribution 60% Men Peak of Disease Onset: years Bibleclass , Brunner 3
4 PSC & IBD Association PSC & IBD Netherlands: 2/3 PSC patients have IBD, 75% of them Ulcerative Colitis 83% Pancolitis 18% Left-sided Colitis 4% Proctitis But only max. 10% UC patients have PSC!!! Hirschfield, Lancet 2013 Bibleclass , Brunner 4
5 Pathogenesis Morphological Manifestation - Progressive and chronic injury occurs in bile ducts - Inflammatory & concentric periductal fibrosis Hirschfield, Lancet Several strictures with intervening saccular dilatations Bibleclass , Brunner 5
6 Pathogenesis Bile Acid Toxicity Environment Immunsystem Genetics Hirschfield, Lancet 2013 Bibleclass , Brunner 6
7 Genetics Half of the PSC Susceptibility Loci are common with IBD Functional Importance of Genom-Association? Karlsen, J Hepa
8 Concepcion, Front Physiol 2014 Bile Acid Toxicity Prevention Biliary Bicarbonate Umbrella Cholangiocyte apical glycocalyx Farnesoid X receptor Bibleclass , Brunner 8
9 Immunsystem Like in IBD: Gut-primed adaptive and innate immune responses > chronic and progressive biliary inflammation Involved Cells: effector T-memory cells, B-cells, natural killer cells, macrophages Homing of T-cells into the Liver Bibleclass , Brunner 9
10 Diagnosing PSC Clinical Presentation Jaundice, Itching Fatigue Cholangitis Gallstones Lab Findings Alkaline Phosphatase panca (ANA) (SMA) (IgG) (IgG4) Imaging MRCP ERCP (US) Bibleclass , Brunner 10
11 MRCP, ERCP Bibleclass , Brunner 11
12 Differential Diagnosis Secondary Sclerosing Cholangitis Biliary calculi Chronic biliary infection Cholangiocarcinoma Biliary tract surgery Caroli s Disease Biliary toxin exposure Chronic portal-vein thrombosis Ischaemic stricturing Bibleclass , Brunner 12
13 Treatment Drugs Endoscopy OLT Long term AB in recurr. cholangitis Urso no clear benefit Pruritus: Cholestyramin, Rifampicin,Naltrexon ERCP for Cholangitis, dominant strictures Surveillance MELD Indication Standard Exception (Pruritus, recurrent cholangitis, CCA) 13
14 PSC, UC & Colon Cancer Colon Cancer PSC & UC Colon Cancer UC alone Years Cumulative Risk Years Cumulative Risk 10 9% 10 2% 20 31% 20 5% 25 50% 25 10% Broome, Hepatolgy 1995 PSC & UC Risk for CRC 4.6 x elevated 2/3 of CRC located in the right Colon After OLT 10x elevated Risk than after OLT for other indications Bibleclass , Brunner 14
15 Algorithm Colon Surveillance Screening-Colonoscopy When Diagnosing PSC Colitis? -Endoscopy -Histology PSC without Colitis Surveillance every 5 years PSC with Colitis Surveillance annually!!!
16 Koloskopie Konventionell Weisslicht Random 4-Quadranten- Biopsie alle 10cm - mindestens 30 Biopsien Biopsien sichtbarer Läsionen Chromendoskopie Indigokarmin Biopsien sichtbarer Läsionen
17 PSC & Biliary Tumors CCA Risk in PSC Annual risk for CCA 2% Cumulative incidences: 6% 11% after 10y. 20% after 30y. Rizvi, Clin Gast Hepa % 37% of CCA are detected within the first after diagnosis Bibleclass , Brunner 17
18 CCA Screening Algorithm Bibleclass , Brunner 18
19 OLT for CCA: the Mayo Protocol Criteria for Inclusion Confirmed perihilar CCA Diameter < 3cm No intra- or extrahepatic tumor spread Protocol Radiosensitizing Chemotherapy with 5-FU External Radiation Therapy Brachytherapy with endoscopically placed iridium-192 beads Maintenance chemotherapy with capecitabine Laparotomy OLT Bibleclass , Brunner 19
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