Primary Sclerosis Cholangitis

Background/Epidemiology

  • Cholestatic liver disease caused by diffuse inflammation and fibrosis, which may involve the entire biliary tree, leading to the inflammation and destruction of both intra- and extra-hepatic bile ducts and ultimately biliary cirrhosis, portal hypertension and liver failure
    • Also increased risk of cholangiocarcinoma
  • Thought to be autoimmune in nature although evidence is uncertain
  • ~6-7/100,000 (incidence); twice as common in young men (25-40), although relatively common cause of liver failure in children too

Causes

  • Whilst the causes of Primary disease is unknown, there are several causes for secondary sclerosing disease which should be excluded before the diagnosis of PSC is made e.g.
    • Previous bile duct surgery with stricturing and cholangitis
    • Bile duct stones causing cholangitis
    • Intra-hepatic infusion of 5-fluorodeoxyuridine (cancer)
    • Autoimmune pancreatitis or IgG4-cholangitis
    • AIDS + cytomegalovirus
  • Association with HLA subtypes; perinuclear antineutrophil cytoplasmic antibodies in 60-60% (p-ANCA)
    • Also found in autoimmune hepatitis

Pathophysiology

  • Unknown but often associated with ulcerative colitis (2/3 of patients with PSC- these patients are also at higher risk of GI/biliary maligancy)
    • A range of other diseases can also be associated e.g. Crohn’s; pancreatitis; retroperitoneal fibrosis; sjogren’s syndrome; autoimmune haemolytic anaemia; autoimmune pancreatitis/IgG4 cholangitis

Presentation

  • May be asymptomatic (with abnormal LFTs/hepatomegaly)
  • Fatigue, intermittent jaundice, weight loss, right upper quadrant pain and pruritus
  • Hepatomegaly, splenomegaly, right upper quadrant tenderness
  • In late disease, patients may present with end-stage liver disease/cirrhosis

Investigations

  • LFTs
    • usually cholestatic biliary picture i.e. raised alk phos
      • note bilirubin is really only elevated in active cholangitis/severe/late disease
      • elevation in transaminases and gGT are also seen but are usually relatively less
    • Hypoalbuminaemia and clotting abnormalities are only seen in late/end-stage disease
  • Antibodies
    • p-ANCA may be of use (consider checking others if suspicious of autoimmune hepatitis or primary sclerosing cholangitis)
  • MRCP
    • Multiple irregular stricturings and dilatations
  • Liver Biopsy

Management

  • UDCA can be used (probably reduces the risk of cholangiocarcinoma) but there is no cure and most patients will reach end-stage disease after around 12 years (most patients die of liver failure)
    • Transplant is an option but, in most cases, PSC can recur in around 20%
      • Cholangiocarcinoma is a contraindication for transplant
    • Avoid alcohol
  • Obstructions can be treated with stenting and infections with antibiotics
  • Osteoporosis often occurs in PSC patients and so bisphosphonate treatment should be considered
  • Vitamin replacement may be required in acutely jaundiced patients

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