Autoimmune Liver Disease

The answer first

Autoimmune liver disease is a family of three conditions in which the immune system attacks the liver. They are not interchangeable. Each has a different target, a different laboratory fingerprint, and a different treatment. Know the discriminator for each, and the whole topic becomes one decision tree. [1]

• Primary biliary cholangitis (PBC) — a T-cell attack on the small interlobular bile ducts, in a middle-aged woman, with a raised ALP, a raised IgM, and an antimitochondrial antibody (AMA) that is positive in around 95 percent. Treatment is ursodeoxycholic acid (first line for all stages) with obeticholic acid or a fibrate added for the inadequate responder.
• Primary sclerosing cholangitis (PSC) — a fibrosing inflammation of the medium and large bile ducts, in a young or middle-aged man with ulcerative colitis, with a raised ALP, a normal IgM, a negative AMA, and a beaded, multifocal-stricturing cholangiogram. There is no effective medical therapy; management is cancer surveillance and ERCP for dominant strictures.
• Autoimmune hepatitis (AIH) — an attack on the hepatocytes, in a young woman (or anyone), with a hepatocellular LFT pattern (transaminases two to ten times the upper limit), a high IgG, and ANA/SMA (type 1) or anti-LKM1 (type 2). Histology shows interface hepatitis with plasma cells. Treatment is prednisolone plus azathioprine. [1]

The single organising principle: classify the disease by the LFT pattern and the autoantibody panel before reaching for a treatment. A cholestatic pattern with a positive AMA is PBC until proven otherwise. A cholestatic pattern with IBD and a normal AMA is PSC until proven otherwise. A hepatocellular pattern with a high IgG is AIH until proven otherwise. The overlap syndromes sit at the intersections. [1]

DWE high-yield: The three diseases are distinguished by the combination of (1) the LFT pattern, (2) the key antibody, (3) the immunoglobulin, and (4) the histology. Most aetiology MCQ stems can be answered from those four data points alone. PBC and PSC are cholestatic (raised ALP); AIH is hepatocellular (raised ALT/AST). PBC has AMA and raised IgM; PSC has neither; AIH has ANA/SMA or anti-LKM1 and raised IgG [1][6].

---

References10Show ledgerHide ledger

1. [1]Kaplan MM, Gershwin ME Primary biliary cirrhosis N Engl J Med, 2005.PMID 16177252
2. [2]Poupon RE, Poupon R, Balkau B Ursodiol for the long-term treatment of primary biliary cirrhosis. The UDCA-PBC Study Group N Engl J Med, 1994.PMID 8152446
3. [3]Nevens F, Andreone P, Mazzella G, et al. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis N Engl J Med, 2016.PMID 27532829
4. [4]Hirschfield GM, Karlsen TH, Lindor KD, Adams DH Primary sclerosing cholangitis Lancet, 2013.PMID 23810223
5. [5]Manns MP, Bergquist A, Karlsen TH, et al. Primary sclerosing cholangitis Nat Rev Dis Primers, 2025.PMID 40082445
6. [6]Manns MP, Czaja AJ, Gorham JD, et al. Diagnosis and management of autoimmune hepatitis Hepatology, 2010.PMID 20513004
7. [7]Krawitt EL Autoimmune hepatitis N Engl J Med, 2006.PMID 16394302
8. [8]Hennes EM, Zeniya M, Czaja AJ, et al. Simplified criteria for the diagnosis of autoimmune hepatitis Hepatology, 2008.PMID 18537184
9. [9]Boberg KM, Chapman RW, Hirschfield GM, et al. Overlap syndromes: the International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue J Hepatol, 2011.PMID 21067838
10. [10]Souza M, Lima LCV, Al-Sharif L, et al. Incidence of Hepatobiliary Malignancies in Primary Sclerosing Cholangitis: Systematic Review and Meta-analysis Clin Gastroenterol Hepatol, 2025.PMID 39709139