Primary Biliary Cholangitis

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease with progressive destruction of small intrahepatic bile ducts.

• Prevalence 1 to 4 per 10,000, with 90% women and onset at 40 to 60 years.
• Anti mitochondrial antibodies (AMA, anti PDC E2) are present in 95%.
• Associations: Sjögren syndrome, autoimmune thyroid disease, systemic sclerosis, coeliac disease.
• Progression to cirrhosis over 10 to 20 years without treatment. Poor prognostic factors are young age, male sex and incomplete ursodeoxycholic acid response.
• Complications: osteoporosis, fat soluble vitamin deficiency, hyperlipidaemia, portal hypertension, HCC (mainly cirrhotic men).

• Fatigue (70%) and pruritus (50%), which can be severe and nocturnal.
• Many are asymptomatic with isolated raised alkaline phosphatase.
• Jaundice, xanthelasma, hyperpigmentation, hepatosplenomegaly in later disease.
• Dry eyes and mouth, steatorrhoea, bone pain.

• Two of three criteria: persistently raised ALP, positive AMA (or PBC specific ANA: sp100, gp210), and compatible histology (florid duct lesions, granulomas).
• Biopsy is not needed if AMA positive with raised ALP.
• Ultrasound or MRCP to exclude biliary obstruction. IgM is raised.
• Elastography for fibrosis staging. DEXA, vitamin A, D, E, K levels, lipid profile, TSH.
• Response assessment at 12 months: Paris II (ALP at or below 1.5 times normal, AST at or below 1.5 times normal, normal bilirubin) or ALP above 1.67 times normal as inadequate.

• Ursodeoxycholic acid 13 to 15 mg/kg/day in divided doses, lifelong, improves survival (response in 60 to 70%).
• Inadequate response: add obeticholic acid 5 mg daily titrated to 10 mg (avoid in decompensated cirrhosis; worsens pruritus), or fibrates (bezafibrate 400 mg daily, fenofibrate 100 to 200 mg daily). Seladelpar 10 mg daily and elafibranor 80 mg daily are PPAR agonists for inadequate responders.
• Pruritus: cholestyramine 4 g up to three times daily (separate from other drugs by 4 hours), then rifampicin 150 to 300 mg twice daily, naltrexone 25 to 50 mg daily, sertraline 75 to 100 mg. Ileal bile acid transporter inhibitors in trials. Plasmapheresis, nasobiliary drainage for refractory cases.
• Fatigue: exclude thyroid, anaemia, depression, sleep disorder. Modafinil is of limited benefit.
• Osteoporosis: calcium 1000 to 1200 mg, vitamin D, alendronate 70 mg weekly. Replace fat soluble vitamins.
• Sicca symptoms: artificial tears, saliva substitutes.
• Transplantation for bilirubin above 6 mg/dL, decompensation, or intractable pruritus; recurrence in 20 to 30% after 10 years.
• HCC and varices surveillance in cirrhosis.