Autoimmune Cholangiopathies

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1- Introduction

2- Key Definitions

3- Clinical Features & Examination Tips

4- Investigations & Interpretation

5- Pathophysiology

6- Symptoms

7- Treatment

Introduction

Autoimmune cholangiopathies are chronic, immune-mediated diseases affecting the biliary tree—the ducts that drain bile from the liver. The two main types are:

  • Primary Biliary Cholangitis (PBC): Targets small intrahepatic bile ducts; occurs mostly in middle-aged women.

  • Primary Sclerosing Cholangitis (PSC): Affects large intra- and extrahepatic ducts; occurs mostly in young men, often associated with inflammatory bowel disease (IBD), especially ulcerative colitis.

 

Both conditions lead to progressive cholestasis, fibrosis, and eventually cirrhosis and liver failure if untreated.

© image from Wikimedia Commons

Key Definitions

  • Cholangiopathy: Disease of the bile ducts.

  • Cholestasis: Impaired bile flow leading to accumulation of bile acids in the liver and systemic circulation.

  • AMA (antimitochondrial antibody): Autoantibody highly specific for PBC.

 

  • MRCP (Magnetic Resonance Cholangiopancreatography): Non-invasive imaging to visualize bile ducts.

Clinical Features & Examination Tips

Primary Biliary Cholangitis (PBC):

  • Common in women (9:1), median age 50–55

  • Fatigue, pruritus (early); jaundice, xanthomas (late)

  • Associated with other autoimmune diseases (e.g. thyroiditis, Sjögren’s)

  • Right upper quadrant discomfort (rare)

Primary Sclerosing Cholangitis (PSC):

  • Affects men more often (1:3), age 20–40

  • Fatigue, intermittent jaundice, pruritus

  • Strongly linked with ulcerative colitis (~70%)

  • May present with portal hypertension or cholangitis episodes

Investigations & Interpretation

PBC:

  • LFTs: Cholestatic pattern (↑ALP, GGT)

  • Serology:

    • AMA + in >95%

    • ANA and anti-smooth muscle antibody possible

    • Raised IgM

  • Imaging: Normal biliary tree

  • Liver biopsy: Granulomatous portal inflammation (only if AMA–)

 

PSC:

  • LFTs: Cholestatic pattern

  • Serology:

    • pANCA in 65–85% (non-specific)

    • IgG elevation may occur

  • Imaging:

    • MRCP shows “beading” and stricturing

  • Liver biopsy: Onion-skin fibrosis, ductular proliferation

Pathophysiology

In Primary Biliary Cholangitis (PBC), the immune system—particularly CD4+ T cells—targets and gradually destroys the small intrahepatic bile ducts, likely triggered by genetic susceptibility and environmental factors. This immune attack is strongly associated with the presence of antimitochondrial antibodies (AMA), leading to granulomatous inflammation, cholestasis (bile build-up), and progressive fibrosis of the liver parenchyma.

In contrast, Primary Sclerosing Cholangitis (PSC) involves chronic, immune-mediated inflammation of the large intra- and extrahepatic bile ducts, resulting in concentric periductal fibrosis often described histologically as “onion-skin” fibrosis. Over time, this causes multifocal strictures, bile duct obliteration, and secondary biliary cirrhosis. Although the precise autoimmune trigger in PSC is unknown, it is strongly associated with ulcerative colitis and often features pANCA positivity, suggesting systemic immune dysregulation.

Both conditions impair bile flow, induce liver cell injury, and can progress to cirrhosis and end-stage liver disease if untreated

Primary Sclerosing Cholangitis (© image from librepathology)
Primary Biliary Cholangitis (© image from librepathology)

Symptoms

  • Primary Biliary Cholangitis (PBC)

    • Early signs:

      • Fatigue

      • Pruritus (itching)

    • Later signs:

      • Jaundice

      • Right upper quadrant discomfort (rare)

      • Xanthelasma and xanthomata (fat deposits in skin)

      • Features of other autoimmune diseases (e.g. dry mouth, thyroid disease)

     

  • Primary Sclerosing Cholangitis (PSC)

    • Fatigue

    • Recurrent jaundice

    • Intermittent right upper quadrant pain

    • Pruritus

    • Signs of cholangitis (fever, rigors)

    • Advanced disease: cirrhosis, portal hypertension, cholangiocarcinoma risk

    • Strongly associated with ulcerative colitis

Treatment

PBC

  • Ursodeoxycholic acid (UDCA): First-line therapy (13–15 mg/kg/day)

  • Obeticholic acid: For UDCA non-responders

  • Symptomatic treatment:

    • Pruritus: Cholestyramine (first-line), rifampicin if resistant

    • Bone disease: Calcium + vitamin D, bisphosphonates

  • Overlap with autoimmune hepatitis: May benefit from corticosteroids (Davidson 24e, p. 899)

PSC

  • No effective medical cure

  • UDCA is used but benefits are limited

  • Monitor for cholangitis, strictures, cholangiocarcinoma

  • Colonoscopy every 1–2 years if IBD present (risk of colorectal cancer)

  • Liver transplant: Only definitive treatment in end-stage liver disease

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