primary sclerosing cholangitis and primary biliary cirrhosis l.
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Primary Sclerosing Cholangitis and Primary Biliary Cirrhosis. Registrar teaching July 2007 Paul Frankish. Primary Biliary Cirrhosis PBC-introduction. Slowly progressive autoimmune liver disease 90% females Peak incidence in 40’s

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Primary Sclerosing Cholangitis and Primary Biliary Cirrhosis

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primary sclerosing cholangitis and primary biliary cirrhosis
Primary Sclerosing Cholangitis and Primary Biliary Cirrhosis
  • Registrar teaching July 2007
  • Paul Frankish
primary biliary cirrhosis pbc introduction
Primary Biliary Cirrhosis PBC-introduction
  • Slowly progressive autoimmune liver disease
  • 90% females
  • Peak incidence in 40’s
  • Portal inflammation and autoimmune destruction of intrahepatic bile ducts
  • Leads to cirrhosis and liver failure
  • 90-95% have antimitochondrial antibody
clinical features
Clinical features
  • ~50% asymptomatic at diagnosis
  • Fatigue and pruritus most commonn symptoms~20%
  • Hyperlipidaemia,hypothyroidism,osteopenia,autoimmune diseases
  • Portal hypertension ,liver failure,HCC
physical examination
Physical examination
  • Often normal
  • Spiders and skin excoriations
  • Xanthelasmas
  • Hepatomegaly ~70%
  • Jaundice (late)

3 criteria

Positive AMA

Abnormal LFT

Compatible biopsy

pathological stages 4
Pathological Stages (4)
  • 1 Destruction of bile ducts in portal tracts
  • 2 Inflammation beyond portal tracts
  • 3 fibrous septa link portal triads
  • Cirrhosis
epidemiology and genetic factors
Epidemiology and Genetic factors
  • Most prevalent in Nth Europe.10 fold variation
  • More common in first degree relatives
  • Molecular mimicry to certain bacteria or viruses
  • Environmental chemical exposure
autoimmune responses
Autoimmune responses
  • Targets of antimitichondrial antibodies
  • 4 autoreactive mitochondrial antigens
  • Pyruvate dehydrogenase E2 complex PDC-E2
  • E-3 binding protein E3-BP
  • Ketoglutaric acid dehydrogenase E2 complex OGDC-E2
  • 2 oxo-aciddehydrogenaseE-2 complex BCKD-E2
t cell response
T cell response
  • T cells infiltrating the liver are specific for PDC-E2
  • Nature of bile duct injury not fully elucidated
treatment ursodeoxycholic acid
Treatment:-Ursodeoxycholic acid


Given in dose 12-15 mg/kg

Reduces bilirubin,ALP,AST,ALT cholesterol and IgM

Meta-analysis of 3 trials 548 patients UDCA reduced risk of liver transplantation or death over 4 years

Delays fibrosis and varices

Does not work in advanced disease

other drugs
Other drugs
  • Colchicine
  • Methotrexate
  • Budesoide
liver transplantation
Liver transplantation
  • Only effective Rx for liver failure
  • Survival is excellent 85% at 5 years


A chronic inflammatory cholestatic disease

Progressive destruction of bile ducts

May progress to cirrhosis

Aetiology unknown

epidemiology natural history and prognosis
Epidemiology,Natural History and Prognosis
  • Prevalence 6-8/100000
  • Usually diagnosed in 20s and 30s
  • Male predominance ~3:1
  • 80% have IBD –usually UC
  • ~44% asymptomatic at diagnosis
  • Median survival ~ 12 years
ibd and psc
  • Mainly associated with UC ~85%-the rest Crohns or indeterminate colitis
  • 4% UC patients will develop PSC
  • No correlation between activity of IBD and PSC
aetiology and pathogenesis
Aetiology and Pathogenesis
  • Familial incidence
  • HLA associations-B8,DR3,DRw52a,DR2,DR4
  • Polymorphism of TNF gene
immune factors
Immune factors
  • frequency autoimmune disorders
  • T cells in blood and liver
  • circulating immune complexes
  • 95% patients with PSC have at least one autoantibody
  • 85% +ve ANCA
  • 50% +ve ANA
  • 25% +ve SMA
  • Association between PSC and UC suggests a pathogenic interaction
  • ?bacteria or toxic substances absorbed via inflammed mucosa
  • Bile duct injury suggest ischaemic injury ?immune complex mediated
clinical manifestations
Clinical Manifestations
  • 44% asymptomatic but most develop symptoms over time
  • Pruritis,jaundice,pain and fatigue are common symptoms
  • Later on develop symptoms of cirrhosis and portal hypertension
  • Lifetime prevalence of 10-30%
  • Annual risk 1.5% per year
  • Difficult to diagnose
  • Patients also have late risk of HCC
psc and bowel cancer
PSC and Bowel cancer
  • 25% PSC develop cancer or dysplasia cf 5.6% with UC alone
  • Cancers associated with PSC tend to be more proximal,are more advanced at diagnosis and mre likely to be fatal
  • Need aggressive colonoscopic surveillance
  • Cholangiography-either MRCP or ERCP
  • Clinical,biochemical and histological features
ercp and mrcp
  • Typical features:-

multifocal strictures and dilatation

usually affects both intra and

extrahepatic ducts

liver biopsy
Liver biopsy
  • Useful for staging disease
  • “Onion skin fibrosis” only in ~10% biopsies
  • ~5% patients have typical biopsy features with a normal cholangiogram
lab tests
Lab tests
  • LFTs-cholestatic pattern:ALP 3-5x ULN

-AST/ALT slightly elevated only

-raised bilirubin may occur with advanced disease,dominant stricture,cholangioca,stones,cholangitis

  • Many strategies tried but only transplantation shown to improve survival
ursodeoxycholic acid
Ursodeoxycholic acid
  • Causes significant biochemical improvement
  • Little symptomatic or clinical benefit
  • May need high doses
  • Major role may be to reduce bowel cancer risk in patients with PSC/UC
  • Not funded in NZ !
  • No long term data
  • Serious risk of bone disease
  • Colchicine, D-Penicillamine, Nicotine of no benefit
  • Combination Rx with UDCA Aza and steroids showed clinical and biochemical improvement in a small trial
endoscopic treatment
Endoscopic treatment
  • Direct injection of steroids into biliary tree ineffective
  • Balloon dilation or stenting can improve clinical,biochemical and cholangiographic appearances
  • Some reports of survival advantages and delay to liver transplantation
liver transplant
Liver Transplant
  • Only treatment to improve overall survival
  • Improves quality of life in 80% patients
  • 10 year survival post OLT ~70%
  • Aim to transplant before cholangica
  • Recurrent PSC in ~ 4% of grafts