Autoimmune and Cholestatic Liver Disease

• Audio chapter
  Single-voice audio, listen on the commute.
• ABIM-format MCQs
  5-option vignettes with full wrong-answer teaching.
• Study guide
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What this chapter covers

• Section 20.1: Sorting AIH, PBC, and PSC

  The three classical immune liver diseases all result from loss of tolerance to a self-antigen, and they differ in the cell type the immune system attacks.

• Section 20.2: AIH diagnosis, histology, and treatment

  Autoimmune hepatitis is the immune attack on hepatocytes by activated T cells responding to self-antigens that have escaped tolerance, with B-cell-derived autoantibodies serving as serologic markers rather than effectors.

• Section 20.3: PBC diagnosis, histology, and natural history

  Primary biliary cholangitis is a slowly progressive autoimmune cholangiopathy in which T cells attack the small intralobular bile duct epithelium and produce a destructive non-suppurative cholangitis with progressive ductopenia and fibrosis.

• Section 20.4: PBC first-line and second-line therapy

  The PBC treatment algorithm starts with universal use of UDCA, then escalates by biochemical response, with two FDA-approved second-line agents that target nuclear receptors involved in bile acid homeostasis (elafibranor and seladelpar); obeticholic acid, the original 2016 second-line agent, was voluntarily withdrawn from the U.S. market in September 2025 at the FDA's request because of liver-injury signals, and its approval was formally withdrawn on November 24, 2025.

• Section 20.5: PBC pruritus management

  Pruritus is the most common symptom in PBC, frequently precedes biochemical disease, and worsens disability scores more than fatigue in many patients.

• Section 20.6: PSC diagnosis and natural history

  Primary sclerosing cholangitis is the chronic immune-mediated inflammation and fibrotic stricturing of the intra and extrahepatic bile ducts, producing the classic multifocal stricture pattern with intervening normal-caliber duct segments that gives the cholangiogram its beaded appearance.

• Section 20.7: PSC complications and surveillance

  PSC is a premalignant condition with three associated cancers (cholangiocarcinoma, gallbladder cancer, and colorectal cancer in PSC-IBD), each with specific surveillance intervals and modalities.

• Section 20.8: IgG4 sclerosing cholangitis and overlap syndromes

  This section covers the disease that mimics PSC but behaves differently, plus the two overlap syndromes that blur the AIH-PBC-PSC boundaries.

Podcast episodes

1. 01

   Immune Liver Disease: Autoimmune Hepatitis

   Autoimmune hepatitis is first placed among the three immune liver diseases using the biochemical pattern, demographics, and antibodies, and only then confirmed. The episode explains why a mild-looking case can already be cirrhotic, how type one differs from type two, why the simplified score often needs a biopsy to reach definite, and why the drug history is checked before long-term treatment is committed. Treatment follows: prednisone or budesonide with azathioprine after TPMT testing, with budesonide kept out of cirrhosis. The episode then turns to the most common error, stopping too soon, and ends with azathioprine failure, acute severe disease, and pregnancy.

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2. 02

   Cholestatic Liver Disease: Diagnosis to the Itch

   Primary biliary cholangitis is autoimmune destruction of the small bile ducts, aimed at a mitochondrial enzyme that the anti-mitochondrial antibody recognizes. The episode first makes the diagnosis from labs without a biopsy, then looks for associated conditions and sets the alkaline phosphatase as the marker to follow. It covers the antibody-negative and antibody-only edges of diagnosis. It then turns to ursodeoxycholic acid dosing, response judged at twelve months, and second-line choices after obeticholic acid's withdrawal. Transplant timing follows. The last section treats itch on its own terms, stepping from cholestyramine through rifampin, naltrexone or sertraline, and linerixibat.

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3. 03

   Cholestatic Liver Disease: Sclerosing Cholangitis

   Primary sclerosing cholangitis is an imaging diagnosis and a premalignant condition, and the episode builds on that idea. It starts with who gets the disease and why MRCP, not ultrasound, antibodies, or ERCP, makes the diagnosis, then covers when to biopsy, the IgG4 stain, and small-duct disease. It then turns to surveillance for cholangiocarcinoma, colorectal cancer, and gallbladder cancer, the sampling of a dominant stricture, and the complications and treatments, including transplant. Next comes IgG4-related cholangitis, the steroid-responsive mimic of pancreatic cancer, diagnosed with the HISORt criteria. The episode ends with the overlaps of autoimmune hepatitis with primary biliary cholangitis and with sclerosing cholangitis.

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Key topics

• ·Three immune liver diseases compared
• ·Pathogenesis and presentation
• ·Type one versus type two
• ·Simplified scoring and biopsy
• ·Drug-induced autoimmune-like injury
• ·Low-titer smooth muscle antibody in fatty liver
• ·Induction with prednisone or budesonide plus azathioprine
• ·Remission and timing of withdrawal
• ·Azathioprine failure, acute severe disease, and pregnancy
• ·Autoimmune destruction of small bile ducts
• ·Three lab criteria for diagnosis
• ·Associated autoimmune disease and osteoporosis
• ·Lipoprotein X and statin decisions
• ·Histologic stages
• ·AMA-negative disease and AMA-only patients
• ·Ursodeoxycholic acid dosing and response criteria
• ·Second-line PPAR agonists and fibrates
• ·Transplant indications
• ·Stepped treatment of cholestatic itch
• ·Who gets primary sclerosing cholangitis
• ·Why labs and ultrasound cannot settle it
• ·MRCP versus ERCP
• ·Biopsy indications and the IgG4 stain
• ·Small-duct disease
• ·Cholangiocarcinoma and dominant strictures
• ·Colorectal and gallbladder cancer surveillance
• ·Complications, treatments, and transplant
• ·IgG4-related sclerosing cholangitis
• ·Autoimmune hepatitis overlap syndromes