Primary Biliary Cirrhosis / Cholangitis

Condition

A chronic, non-suppurative cholangitis of unknown cause, mainly affecting the interlobular bile ducts, leading to portal hypertension and cirrhosis. Mainly affects women over 40.

Associated with autoimmune conditions: scleroderma, Sjögren syndrome, sarcoidosis, autoimmune hepatitis.

History and examination

May be asymptomatic at diagnosis (suspicion raised by abnormal cholestatic liver tests). May present with fatigue, pruritus, or jaundice.

Investigations

LFTs: cholestatic pattern with raised globulin. Autoantibodies: antimitochondrial antibody (AMA), antismooth muscle antibody (ASMA), antinuclear antibody (ANA). Non-invasive hepatobiliary imaging (usually ultrasound, may need MRCP). Liver biopsy shows non-suppurative destructive cholangitis and destruction of interlobular bile ducts.

Management

Refer to a specialist. HAV and HBV vaccination; avoid alcohol. Ursodeoxycholic acid (UDCA) daily for patients with abnormal liver enzymes — remains first-line.

For inadequate biochemical response to UDCA, two second-line options received FDA accelerated approval in 2024: elafibranor (PPAR-alpha/delta agonist) and seladelpar (PPAR-delta agonist), both showing significant improvement in ALP and pruritus. Obeticholic acid — an older second-line option — has been progressively restricted since 2018 (boxed warning, contraindicated in cirrhosis) and was voluntarily withdrawn from the market in September 2025 due to hepatotoxicity concerns, even in non-cirrhotic patients.