Autoimmune liver disease — distinguishing PBC, PSC and AIH viva

Opening scenario

The examiner presents a 52-year-old woman with fatigue, severe nocturnal pruritus and sicca symptoms; LFTs show ALP 420 U/L (ALT 56) and AMA positive. "What is the diagnosis, how would you confirm it, and what is the management?"^[1][2]

Q1 — Diagnosis and confirmation (2 min)

• Diagnosis: primary biliary cholangitis (PBC). Predominantly female, cholestatic ALP-dominant picture, fatigue, pruritus, dry-gland symptoms, antimitochondrial antibody.^[1][2]
• AMA is the key diagnostic marker. Diagnosis is usually based on cholestatic hepatitis liver tests plus circulating AMA. Anti-gp210 and anti-sp100 carry diagnostic and prognostic weight and matter most in AMA-negative disease. About half of patients are completely asymptomatic at diagnosis today.^[1][2]
• Defend against PSC: PSC is multifocal strictures of intra- and extra-hepatic ducts, UC in 60 to 80%, MRCP preferred, no proven disease-modifying drug.^[6]

Q2 — Why small ducts, and what happens if untreated? (2 min)

• PBC is an autoimmune epithelitis of small intrahepatic bile ducts. Untreated, it culminates in end-stage biliary cirrhosis.^[1][2]
• Pruritus is managed stepwise: cholestyramine first, then rifampicin (Hellenic); AASLD/EASL also list naltrexone then sertraline. Only LPA/autotaxin consistently correlate with itch intensity in the Trivella review — do not invent a receptor viva if you have not sourced it.^[2][14]

Q3 — Management ladder (2 min)

1. First-line: ursodeoxycholic acid 13 to 15 mg/kg/day. Reassess at 6 to 12 months with GLOBE or UK-PBC. Deep response: bilirubin under 0.6 times ULN plus normal ALP.^[2]
2. If inadequate: Hellenic 2026 recommends add-on elafibranor or seladelpar; fibrates off-label if PPAR agonists are unavailable. Do not start OCA in decompensated disease (hepatic decompensation risk); Hellenic additionally notes EMA/FDA revocation of OCA access.^[2]
3. Care is structured, life-long and individualised (EASL 2017).^[1]

Q4 — The other two diseases (2 min)

• PSC: UC in 60 to 80%; MRCP; cholangiocarcinoma lifetime 10 to 20%; colonoscopy every 1 to 2 years if UC; high-dose UDCA 28 to 30 mg/kg/day harmed patients (Lindor: primary endpoint 2.3 times greater); transplant is the only cure, recurrence up to one-third. IgG4-SC is the steroid-responsive mimic in older men with autoimmune pancreatitis.^[5][6][8]
• AIH: hepatitic; score autoantibodies, IgG, histology, viral exclusion (Hennes: 6 or more = 88% sensitivity / 97% specificity in validation). Prednisolone 0.5 to 1 mg/kg/day plus azathioprine 1 to 2 mg/kg/day; budesonide 9 mg/day equivalent (3 mg three times daily) only if non-cirrhotic. Relapses are common; treatment is usually long-term.^[10][11][19]

The one-liner the examiner wants: "PBC and PSC are cholestatic (ALP); AIH is hepatitic (ALT). UDCA for PBC, nothing proven for PSC, steroids for AIH."^[2][6][10]

References9ShowHide

1. [1]European Association for the Study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis J Hepatol, 2017.PMID 28427765
2. [2]Dalekos GN, Gatselis N, Androutsakos T, et al. Consensus statements of the Hellenic Autoimmune Liver Diseases Study Group on the diagnosis and current management of primary biliary cholangitis Ann Gastroenterol, 2026.PMID 41868880
3. [5]Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis Hepatology, 2009.PMID 19585548
4. [6]Malik S, Dbouk N, Grant LM, Samant H. Primary Sclerosing Cholangitis StatPearls, 2026.PMID 30725866
5. [8]Khoury NC, Birk JW. A Review of IgG4-related Sclerosing Cholangitis (IgG4-SC) J Clin Gastroenterol, 2024.PMID 38385591
6. [10]Hennes EM, Zeniya M, Czaja AJ, et al. Simplified criteria for the diagnosis of autoimmune hepatitis Hepatology, 2008.PMID 18537184
7. [11]Manns MP, Woynarowski M, Kreisel W, et al. Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis Gastroenterology, 2010.PMID 20600032
8. [19]Dalekos GN, Arvaniti P, Gatselis NK, et al. Long-term results of mycophenolate mofetil vs. azathioprine use in individuals with autoimmune hepatitis JHEP Rep, 2022.PMID 36411768
9. [14]Trivella J, Levy C. Safety considerations for the management of cholestatic itch Expert Opin Drug Saf, 2021.PMID 33836644