2014 crohns colitis assoc concord hospital forum psc rupert leong

Rupert WL Leong Rupert WL Leong MBBS, MD, FRACP, AGAF MBBS, MD, FRACP, AGAF

Concord HospitalAssociate Professor UNSW

Bankstown Hospital, Sydney, Australia

What is the bile duct?What is the bile duct?

intra-hepatic bile ductintra-hepatic bile duct

extra-hepatic bile ductextra-hepatic bile duct

Bile: digestion of food; stored in gallbladder

Normal PSCPSC

Primary Sclerosing Cholangitis Primary Sclerosing Cholangitis

– idiopathic– strictures, beading– fibrosis, inflammation– cholestasis

• itchy skin, jaundice• vitamin malabsorption

1LaRusson NF et al. NEJM 84

– associated with IBD

EpidemiologyEpidemiology

• Western: – M 2:1– 30-40’s

– 75% PSC will have IBD (UC > CD)– 4% of IBD will have PSC

– point prevalence: 13 per 100,0001

– incidence: 0.91 per 100,0002

1Kingham J et al. Gastroenterol 04, 2Bambha K et al. Gastroenterol 03

Associated DiseasesAssociated Diseases

• IBD: – UC: milder, more extensive, rectal sparing,

CRC risk1

– rare: Crohn’s colitis, coeliac, sarcoid, thyroiditis

• genetic, molecular:– HLA B8, DR32; DRw52a3, ICAM-14

– MMP5

1Florin Gut 04, 2Donaldson Hepatol 91, 3Prochazka NEJM 92, 4Yang J Hepatol 04, 5Satsangi Gastroenterol 01

DiagnosisDiagnosis

• incidental abnormal LFT

Symptom or Sign Frequency (%)

Fatigue 7575

Pruritus 7070

Jaundice, cholestasis 6565

Weight loss, anorexia 40

Fever 25

Hepatomegaly 55

Splenomegaly 30

Hyperpigmentation 25

Xanthomas 4

DiagnosisDiagnosis

• cholangiography: beading, strictures, pruning – 1MRCP– ERCP:

• “stent” dominant stricture • 18% complication rate2

– CT cholangiogram

1Weber C et al. Endosc 08 ; 2Enns R et al. Can J Gastroenterol 03

PSC

DiagnosisDiagnosis

• liver biopsy: non-specific

Ursodeoxycholic AcidUrsodeoxycholic Acid…fever and inflammation, improve eyesight, keep the liver healthy and break down gallstones.

Ursodeoxycholic AcidUrsodeoxycholic Acid

• primary biliary cirrhosis

• pruritus

• hepatitis

• prevent bowel cancer

• dissolves gallstones

• “harmless” (rarely diarrhoea)

Ursodeoxycholic AcidUrsodeoxycholic Acid

• synthetic– lithocholic acid – 7b-hydroxylation – Fusarium equiseti

UDCA: low – medium doseUDCA: low – medium dose

No Dose Biochemical Histological Mayo score response response or survival

Author N = Dose Biochem response

Histo response

Mayo or survival

Van Thiel 92 48 600mg/d (18/12) Yes N/A N/A

Stiehl 94 20 750mg/d (1yr) Yes Yes N/A

De Maria 96 59 600mg/d (2yr) No No N/A

Lindor 97 105 13-15mg/kg/d (2yr) Yes No No

van Hoogsraten 98 48 10mg/kg/d (2yr) Yes Trend No

Mitchell 01 26 20mg/kg/d (2yr) Yes Yes N/A

Harnois 01 23 25-30mg/kg/d (2yr) Yes Yes Yes3Olsson 05 219 15-23mg/kg/d (5yr) Yes N/A Trend4Cullen 08 31 30mg/kg/d (2yr) Yes N/A Yes

• PSC: 8 – 15mg/kg/d

UDCA: high doseUDCA: high dose

No Dose Biochemical Histological Mayo score response response or survival

Author N = Dose Biochem response

Histo response

Mayo or survival

Van Thiel 92 48 600mg/d (18/12) Yes N/A N/A

Stiehl 94 20 750mg/d (1yr) Yes Yes N/A

De Maria 96 59 600mg/d (2yr) No No N/A

Lindor 97 105 13-15mg/kg/d (2yr) Yes No No

van Hoogsraten 98 48 10mg/kg/d (2yr) Yes Trend No1Mitchell 01 26 20mg/kg/d (2yr) Yes Yes N/A2Harnois 01 23 25-30mg/kg/d (2yr) Yes Yes Yes3Olsson 05 219 15-23mg/kg/d (5yr) Yes N/A Trend4Cullen 08 31 30mg/kg/d (2yr) Yes N/A Yes

• 20 – 30mg/kg/d

1Mitchell Gastroenterol 01; 2Harnois Am J Gastroenterol 01; 3Olsson Gastroenterol 05; 4Cullen. J Hepatol 08

UDCAUDCA

• high dose: 28-30mg/kg/d

1Lindor et al. Hepatol 10

placebo n = 74placebo n = 74 UDCA n =76UDCA n =76

cirrhosis, varices, cholangiocarcinoma, liver transplantation, death

terminated at 6 years

n=15n=15 n=22n=22

high dose UDCA 2.3 x greater risk 1° endpoint (P < 0.01) 2.1 x death, transplantation, minimal listing criteria (P = 0.038)

TreatmentTreatment

• ineffective– steroids, budesonide– colchicine, penicillamine, nicotine– immunomodulators – infliximab, etanercept

– minocycline1, UDCA combinations2

– vedolizumab

1Silveira M et al. Am J Gastroenterol 09; 2Schramm C et al. Ann Int Med 99

ComplicationsComplications

PRIMARY SCLEROSING CHOLANGITIS

CIRRHOSIS

Liver Failure PortalHypertension

MALIGNANCY

Colorectal(UC)

Cholangio-carcinoma

Pancreaticgallbladder

CHOLESTASIS

OsteoporosisFat soluble vitamin

CholangitisStricture

Pruritus

Liver TransplantationLiver Transplantation

• indications: – intractable pruritus, fatigue– recurrent refractory cholangitis– cirrhosis– Mayo Clinic Score > 5

• R = (0.0295 * (age in years)) + (0.5373 * LN(total bilirubin in mg/dL)) - (0.8389 * (serum albumin in g/dL)) + (0.5380 * LN(AST in IU/L) + (1.2426 * (points for variceal bleeding))

– exclude cholangiocarcinoma

Local Data: Local Data: Rosy Wang, Ken Liu, Crispin CorteRosy Wang, Ken Liu, Crispin Corte

• 206 PSC patients– 61% males– median age 41 years – median follow up 19 years (3,868 patient-

years)– 77% with IBD; 23% PSC-alone

ConclusionsConclusions

• PSC: small proportion of IBD patients– increased cancer risks

• hepatobiliary• colorectal

– intensive surveillance– local data to provide new

recommendations

IBD Concord / BankstownIBD Concord / Bankstown

• 10 years – first IBD clinics– first IBD nurses– continuous clinical drug trials – first mesenchymal stem cells study – first IBD pharmacists – clinical excellence in research

A.McAvoy 22

Australian CrohnAustralian Crohn’’s & s & Colitis AssociationColitis Association

(ACCA)(ACCA)

IBD Clinical Trials

Coordinator Angela McAvoy AM

IBD Concord / BankstownIBD Concord / Bankstown

• new initiatives: – “IBD Sydney” – forum for consultant

gastroenterologists• rural connection via Skype

– support regulatory approval IBD drugs • vedolizumab • infliximab for UC

– “IBD Consensus Working Group” – acute severe ulcerative colitis

Australian Bowel FoundationAustralian Bowel Foundation

• new gastrointestinal foundation – funding IBD nurses – seeding grants for research – charity, tax deductable donations – fellowship funding – investment– education – focus on PSC – registry

• disbursement biomarker patent

• need: – executives– professional associates– ‘professional’ charity organisers

• if interested: [email protected]