Primary biliary cholangitis

Introduction

Primary Biliary Cholangitis (PBC) is a chronic, progressive autoimmune liver disease characterised by destruction of the intrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and eventually liver failure. It predominantly affects middle-aged women and is often detected via abnormal liver function tests before symptoms appear.

Peak Incidence

• Most commonly diagnosed between the ages of 40 and 65.
• Strong female predominance (~90% of cases).

Pathophysiology

• PBC is an autoimmune condition in which CD4+ and CD8+ T lymphocytes target small intrahepatic bile ducts.
• Destruction of bile ducts leads to cholestasis and accumulation of toxic bile acids.
• Persistent cholestasis results in inflammation, fibrosis, and eventual cirrhosis.
• The antimitochondrial antibody (AMA-M2) is highly specific and plays a diagnostic role, though its direct pathogenicity is unclear.

Symptoms

Early Symptoms

• Fatigue – Most common initial complaint.
• Pruritus – Especially at night, due to bile acid accumulation.

Late Symptoms

• Pale stools and dark urine – Due to impaired bile excretion.
• Jaundice – Resulting from hyperbilirubinaemia.
• Xanthomas and xanthelasmas – Due to hyperlipidaemia.

Signs

• Hepatomegaly.
• Splenomegaly – Indicative of portal hypertension.
• Cirrhotic features, including:
  • Ascites.
  • Clubbing.
  • Spider naevi.
  • Variceal bleeding (if portal hypertension is advanced).
• Osteoporosis – Related to impaired fat-soluble vitamin absorption, especially vitamin D.

Diagnosis

Blood Tests

• Liver function tests (LFTs):
  • Elevated ALP and GGT (cholestatic pattern).
  • Mildly raised AST and ALT.
  • Elevated bilirubin in later stages.
  • Low albumin and raised INR in advanced disease.
• Autoantibodies:
  • Antimitochondrial antibody (AMA-M2) – Present in >95% of cases.
  • Antinuclear antibody (ANA) – Present in ~35%.
• Serum immunoglobulins:
  • Raised IgM – Characteristic of PBC.

Imaging

• Ultrasound or MRCP – To exclude extrahepatic biliary obstruction.
• Transient elastography (FibroScan) – To assess fibrosis severity.

Liver Biopsy

• Not routinely needed but may be performed:
  • If AMA-negative.
  • To assess staging in uncertain cases.

Complications

• Portal hypertension:
  • Ascites.
  • Variceal bleeding.
  • Hypersplenism (leading to cytopenias).
• Hepatic encephalopathy.
• Malabsorption of fat-soluble vitamins (A, D, E, K), calcium, and lipids.
  • May lead to osteoporosis and coagulopathy.
• Hepatocellular carcinoma (HCC) – Increased risk, particularly in cirrhotic patients.

Management

First-Line Therapy

• Ursodeoxycholic acid (UDCA) – Delays progression, improves liver biochemistry and survival.

Second-Line Options

• Obeticholic acid – Recommended if inadequate response to UDCA.
• Fibrates (e.g. bezafibrate, fenofibrate) – May be used as add-on therapy in selected cases.

Symptomatic Treatment

• Pruritus – First-line: cholestyramine (bile acid sequestrant).
• Osteoporosis prevention:
  • Calcium and vitamin D supplementation.
  • Bisphosphonates if osteoporosis confirmed.
• Hyperlipidaemia – May require statins.

Definitive Treatment

• Liver transplantation – Indicated for:

  • End-stage liver disease (e.g. decompensated cirrhosis).
  • Refractory pruritus.
  • Bilirubin >100 µmol/L or other features of poor prognosis.