Primary Biliary Cholangitis
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Direct answer
Life-long ursodeoxycholic acid at 13–15 mg/kg/day is the treatment of primary biliary cholangitis, started at diagnosis in every patient, with the one-year response checked against Paris II criteria (ALP at or below 1.5 times the upper limit, AST at or below twice normal, and a normal bilirubin). The diagnosis stands on a cholestatic ALP in a middle-aged woman with a positive antimitochondrial antibody — sensitivity around 95 per cent — and biopsy is reserved for antibody-negative or atypical cases. Inadequate responders step up to obeticholic acid or fibrates, keeping in mind that obeticholic acid is contraindicated in decompensated cirrhosis. Pruritus is treated down a fixed ladder that begins with cholestyramine, and every cirrhotic patient enters six-monthly hepatocellular carcinoma surveillance.
What you must remember
- Diagnostic pair: cholestatic biochemistry plus antimitochondrial antibody at a titre of 1:40 or more; the M2 subtype is specific, and sp100 or gp210 antibodies rescue the 5 per cent who are AMA-negative.
- Epidemiology: nine women for every man, peak age 40–60; fatigue and pruritus precede jaundice by years, and up to half are asymptomatic at detection.
- UDCA dose: 13–15 mg/kg/day in divided doses — a viva favourite; too small a dose is the commonest reason for "non-response".
- Response check at 12 months: Paris II for early disease (ALP ≤1.5 × ULN, AST ≤2 × ULN, normal bilirubin); Paris I, UK-PBC and GLOBE scores risk-stratify the inadequate responder.
- Second line: obeticholic acid 5–10 mg (contraindicated in decompensated cirrhosis and portal hypertension), or bezafibrate 400 mg as an add-on; elafibranor and seladelpar are recent per current guidance.
- Pruritus ladder: cholestyramine 4 g separated from UDCA by at least four hours, then rifampicin 150–300 mg, then naltrexone, then sertraline; refractory cases go to albumin dialysis or transplant assessment.
- Bone disease: osteoporosis not osteomalacia is the classical association — dual-energy X-ray absorptiometry every two years with calcium and vitamin D.
- Associated autoimmunity: sicca, thyroid disease, coeliac disease and vitiligo; check thyroid function at baseline.
Numbers worth knowing
Three clusters of numbers earn marks. The first cluster is diagnostic: an ALP more than 1.5 times normal for over six months with a positive AMA needs no biopsy; if the AMA is negative but clinical suspicion is high, biopsy looking for florid duct lesions — granulomatous destruction of small intrahepatic bile ducts — settles it. The second cluster is therapeutic response: recheck ALP, AST and bilirubin at 12 months. A patient meeting Paris II on UDCA has near-normal survival; one with bilirubin creeping past 2 mg/dL or failing the criteria moves to second-line therapy and transplant discussion, because bilirubin is the strongest survival predictor and the original Mayo risk score was built around it. The third cluster is surveillance: six-monthly ultrasound for hepatocellular carcinoma once cirrhosis or portal hypertension is present, two-yearly bone densitometry for all, and yearly review of itch control — fatigue, unfortunately, responds to no drug.
Where students slip
The classic error is stopping UDCA once the ALP normalises — the drug is for life, and stopping invites biochemical and histological relapse that is harder to recapture. The second is misreading the jaundiced patient: deepening jaundice with itch in PBC can be end-stage disease, but a sudden jump should prompt a search for a dominant stricture or concomitant duct pathology, because PBC does not predispose to cholangiocarcinoma the way PSC does. Finally, do not give obeticholic acid to the ascitic patient — the boxed warning after reports of decompensation is a recognised question stem.
Frequently asked questions
Which two findings diagnose primary biliary cholangitis without biopsy?
Cholestatic ALP elevation for over six months plus antimitochondrial antibody at 1:40 or higher; biopsy is for antibody-negative or doubtful cases.
What is the correct dose of ursodeoxycholic acid?
13–15 mg/kg/day lifelong, in divided doses, taken at least four hours apart from cholestyramine.
How is UDCA response assessed?
At 12 months using Paris II criteria — ALP ≤1.5 times normal, AST ≤2 times normal, normal bilirubin; failure defines the inadequate responder needing second-line therapy.
Why is obeticholic acid contraindicated in decompensated cirrhosis?
It worsened liver failure and portal hypertension in advanced disease, prompting regulatory restriction to compensated patients.
What is the first drug for pruritus in PBC?
Cholestyramine 4 g before and after the morning UDCA dose, escalating before rifampicin, naltrexone and sertraline are considered.