Synopsis
Confirm primary biliary cholangitis, start weight-based ursodeoxycholic acid, identify inadequate response and manage cholestatic symptoms and cirrhosis systematically.
- PBC is a chronic autoimmune destruction of small intrahepatic bile ducts that causes cholestasis, progressive fibrosis and eventually portal hypertension in some patients.
- A persistent alkaline-phosphatase-predominant pattern plus antimitochondrial antibodies usually establishes the diagnosis after extrahepatic obstruction has been excluded.
- PBC-specific antinuclear antibodies, particularly anti-gp210 or anti-sp100 where available, support diagnosis when antimitochondrial antibodies are absent.
- Liver biopsy is not routinely required for a typical antibody-positive case but helps with seronegative disease, suspected AIH overlap or another competing injury.
- Pruritus and fatigue can be severe despite modest liver-test abnormality, while advanced fibrosis may progress with relatively few symptoms.
- Ursodeoxycholic acid at approximately 13 to 15 mg/kg daily is lifelong first-line disease modification and should be started without waiting for symptoms.
- Biochemical response is assessed after adequate UDCA exposure, using alkaline phosphatase, bilirubin and a validated PBC risk model rather than symptoms alone.
- NICE now recommends both elafibranor and, since June 2026, seladelpar for eligible previously treated adults within their marketing authorisations and commissioning arrangements.
- Bile-acid sequestrants can reduce itch but must be separated from UDCA and other medicines because they impair absorption.
- Follow-up is lifelong and includes bone health, thyroid disease, lipid interpretation, portal-hypertension care, hepatocellular carcinoma surveillance where indicated and transplant referral for advanced disease.
Key red flags
Splenomegaly, falling platelets, varices, ascites, jaundice or muscle loss indicates advanced fibrosis or portal hypertension and changes surveillance and transplant planning.
Pain, fever, rigors, abrupt bilirubin rise or dilated ducts suggests stones, stricture or malignancy rather than uncomplicated small-duct autoimmune disease.
Investigation priorities
Confirm persistent cholestasis and establish severity or treatment response.
Management branches
Alkaline phosphatase remains elevated without an obvious transient explanation.
- Repeat and fractionate the clinical problem through medicine, alcohol, pregnancy and symptom review, and assess bilirubin, albumin, INR and platelets.
- Perform ultrasound to exclude dilated ducts, stones or mass and request AMA with immunoglobulins and PBC-specific ANA when appropriate.
- Diagnose a typical antibody-positive case without routine biopsy, but use MRCP or histology when serology, ducts, transaminases or IgG are discordant.
- Stage fibrosis, screen associated conditions and record baseline symptom burden before commencing lifelong disease modification.
PBC is confirmed or strongly established by a specialist.
- Calculate the daily UDCA dose from current weight, choose a licensed formulation and explain that regular long-term use changes prognosis rather than providing immediate symptom relief.
- Review administration, tolerability and adherence and recalculate after meaningful weight change; separate any bile-acid sequestrant by several hours.
- Reassess ALP, bilirubin and liver synthetic markers during treatment and formally evaluate response after an adequate interval using a validated risk model.
Key medicines
Ursodeoxycholic acidUse a licensed PBC formulation at approximately 13–15 mg/kg daily, within the product range of 12–16 mg/kg, divided initially if required and continued indefinitely; recalculate when weight changes.Exclude complete biliary obstruction and follow the exact product advice in advanced disease. Diarrhoea or initial itch can affect adherence; bile-acid sequestrants reduce absorption and require wide dose separation.
SeladelparNICE TA1171 supports use within its marketing authorisation; the current Livdelzi SmPC dose is 10 mg by mouth once daily with or without food, added to UDCA after inadequate response or used alone when UDCA is not tolerated.Specialist initiation and local commissioning apply. Establish hepatic status first; the SmPC does not recommend use with current or prior decompensated cirrhosis and contraindicates complete biliary obstruction. Monitor worsening ALT, AST, bilirubin or ALP and separate from bile-acid resins by at least four hours.