Primary sclerosing cholangitis

Introduction

Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic liver disease characterised by progressive inflammation, fibrosis, and stricturing of the intrahepatic and extrahepatic bile ducts. The condition leads to bile flow obstruction, liver damage, and eventually cirrhosis. Although the exact cause is unknown, PSC is strongly associated with ulcerative colitis, with approximately 70–80% of affected individuals having coexisting inflammatory bowel disease.

Peak Incidence

• Most commonly affects individuals aged 25 to 40 years.
• There is a male predominance.
• Often diagnosed incidentally on abnormal liver function tests.

Pathophysiology

• PSC is believed to have an autoimmune component, but the exact aetiology is unclear.
• It leads to progressive concentric fibrosis of the bile ducts, resulting in strictures and segmental dilatation.
• This produces a “beaded” appearance on cholangiography.
• Over time, this causes cholestasis, hepatocyte damage, and progression to biliary cirrhosis.

Symptoms

PSC is frequently asymptomatic in the early stages and diagnosed on routine blood tests.

When symptomatic, patients may present with:

• Right upper quadrant (RUQ) pain – Dull or intermittent.
• Pruritus – Due to bile acid retention.
• Fatigue.
• Fever – Suggestive of superimposed cholangitis.
• Weight loss and malaise.
• Pale stools and dark urine – Due to cholestasis.

Signs

• Jaundice.
• Hepatomegaly.
• Splenomegaly – From portal hypertension.
• Ascites – In advanced disease.
• Palmar erythema.
• Oesophageal varices – Due to portal hypertension and cirrhosis.

Diagnosis

Blood Tests

• Liver function tests (LFTs):
  • Raised ALP and GGT (cholestatic pattern).
  • Bilirubin rises with disease progression.
• Autoantibodies:
  • p-ANCA – Positive in 60–80% of cases, though non-specific.

Imaging

• MRCP (Magnetic Resonance Cholangiopancreatography):
  • Gold standard for diagnosis.
  • Shows a “beaded” appearance – alternating strictures and dilatations.
• ERCP (Endoscopic Retrograde Cholangiopancreatography):
  • Can confirm similar findings.
  • Also allows for therapeutic intervention (e.g. dilation, stenting).

Liver Biopsy

• Rarely required for diagnosis.
• May show “onion-skin” fibrosis – concentric periductal scarring.

Complications

• Cholangiocarcinoma – Significant increased risk.
• Colorectal cancer – Particularly in those with coexisting ulcerative colitis.
• Recurrent biliary strictures and cholangitis.
• Liver cirrhosis and liver failure.
• Fat-soluble vitamin deficiency – Due to impaired bile flow and absorption (vitamins A, D, E, K).
• Osteoporosis – Secondary to chronic liver disease and vitamin D malabsorption.

Management

There is no definitive medical cure for PSC. Management focuses on symptom control, managing complications, and timely referral for transplantation.

Symptomatic Treatment

• Ursodeoxycholic acid (UDCA):
  • May improve liver biochemistry, but does not significantly alter disease progression.
• Cholestyramine – First-line treatment for pruritus.
• Vitamin supplementation – For fat-soluble vitamin deficiencies.

Endoscopic Therapy

• ERCP with dilation and stenting – For dominant strictures or biliary obstruction.
• Antibiotics – For suspected or confirmed bacterial cholangitis.

Definitive Treatment

• Liver transplantation – The only curative option for end-stage PSC.

  • Indicated for:
    • Decompensated cirrhosis.
    • Recurrent cholangitis.
    • Intractable pruritus.
    • Severe biochemical derangement.
  • PSC may recur post-transplant in up to 20% of patients.