Liver and intrahepatic bile ducts - nontumor
Biliary tract disease
Primary biliary cholangitis

Editor-in-Chief: Debra Zynger, M.D.
Raul S. Gonzalez, M.D.

Topic Completed: 30 December 2019

Minor changes: 30 January 2020

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PubMed Search: Primary biliary cholangitis[TI] liver[TIAB] pathology full text[sb]


Raul S. Gonzalez, M.D.
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Cite this page: Gonzalez R. Primary biliary cholangitis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/liverPBC.html. Accessed June 4th, 2020.
Definition / general
  • Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease with granulomatous destruction of interlobular bile ducts, leading to fibrosis and ultimately cirrhosis
Essential features
  • Typically occurs in middle aged women; extremely rare in children
  • Labs include elevated alkaline phosphatase, elevated IgM and the classic antimitochondrial antibody (AMA)
  • Histologic changes, including the pathognomonic florid duct lesions, can be patchy
Terminology
ICD coding
  • ICD-10: K74.3 - primary biliary cirrhosis
Epidemiology
Sites
  • Involves the most proximal portion of biliary tree, namely the interlobular bile ducts and canals of Hering; larger bile ducts are not typically affected (Hum Pathol 2002;33:983)
Etiology
  • Likely autoimmune; associated with Sjögren syndrome, scleroderma, thyroiditis, rheumatoid arthritis, Raynaud phenomenon, membranous glomerulonephritis, systemic lupus erythematosus, celiac disease
Clinical features
  • 85% are women, usually ages 40 - 60
  • Symptoms include insidious onset of pruritis, malaise, dark urine, light stools, hepatomegaly, xanthomas, and xanthelasma
  • Can develop cirrhosis and die from liver failure
  • Some patients have overlap disease with autoimmune hepatitis; much more rarely, patients may have overlap with primary sclerosing cholangitis (PSC); in overlap, strict criteria for both diseases must be met (ACG Case Rep J 2018;5:e54)
  • Increased risk of hepatocellular carcinoma once cirrhotic but there does not appear to be significant increased risk of cholangiocarcinoma (unlike in primary sclerosing cholangitis)
Diagnosis
  • Two of three of the following criteria are required:
    • Serum alkaline phosphatase > 1.5 times the upper limit of normal, antimitochondrial antibody, liver sample showing nonsuppurative destructive cholangitis and destruction of interlobular bile ducts (Autoimmun Rev 2014;13:441)
    • Other characteristic clinical features include disease-specific antinuclear antibodies (sp100 and gp210), elevated serum IgM, hypercholesterolemia, xanthomas, Sicca syndrome, pruritus, and fatigue (Autoimmun Rev 2014;13:441)
    • Patients who appear to have primary biliary cholangitis except for negative antimitochondrial antibody are said to have AMA-negative primary biliary cholangitis, also called autoimmune cholangitis
Laboratory
  • Elevated serum alkaline phosphatase and IgM, AMA in 95%, elevated conjugated bilirubin (late)
  • M2 form of AMA, present in 90%, is against E2 subunit of pyruvate dehydrogenase complex
Radiology description
  • Parenchymal lace-like fibrosis and periportal halo sign on T2-weighted MRI in some patients (Eur J Radiol 2009;69:523)
Case reports
Treatment
  • Ursodeoxycholic acid and obeticholic acid improve liver function and symptoms but may not halt progression of disease
  • Liver transplant for advanced / cirrhotic cases; may eventually recur in the graft
Gross description
  • Hepatomegaly early; cirrhosis late
Gross images

Contributed by Raul Gonzalez, M.D.

Cirrhotic liver

Microscopic (histologic) description
  • Dense lymphocytic infiltrate in portal tracts with granulomatous destruction and loss of medium sized interlobular bile ducts, focal and variable within the liver
  • May involve sinusoids early
  • Periportal Mallory hyaline late, usually minimal neutrophils, variable portal eosinophils; resembles graft versus host disease and graft rejection; ductules derived from periportal hepatocytes are still present; prominent Ito cells with fat vacuoles
  • Key finding is the florid duct lesion: interlobular bile ducts (within small portal tracts) are destroyed by poorly formed portal epithelioid granulomas
  • Dense lymphocytic infiltrate in portal tracts can also be seen, mimicking hepatitis
  • Ductular reaction and duct injury early; duct loss and lobular cholestasis with feathery degeneration late
  • Lobules may show macrophage aggregates / small granulomas but typically not much of an inflammatory infiltrate
  • The above changes are patchy and may not be present in a given biopsy
  • Nodular regenerative hyperplasia may be seen in early disease (Gastroenterology 1992;102:1319)
  • Staging:
    • Florid duct lesions or portal hepatitis
    • Ductular reaction or periportal hepatitis
    • Bridging/septal fibrosis or bridging necrosis
    • Cirrhosis
Microscopic (histologic) images

Contributed by Raul Gonzalez, M.D.

Portal and duct inflammation

Florid duct lesion

Lobular cholestasis

Lobular macrophages

Ductular reaction

Duct loss

Positive stains
  • Note: None of these stains are routinely used for diagnosis
  • S100: highlights dendritic cells in the basement membrane in early stage disease (Am J Pathol 1989;134:741)
  • CD1a: highlights Langerhans cells in biliary epithelium (Am J Surg Pathol 2012;36:732)
  • Copper stains: positive within hepatocytes in all chronic cholestatic conditions, including PBC
Sample pathology report
  • Liver, biopsy:
    • Biliary pattern injury with mild chronic portal inflammation, ductular reaction, and focal changes suggestive of florid duct lesion (see comment)
    • Comment: The histologic findings, in addition to the patient’s reported history of antimitochondrial antibody, are consistent with primary biliary cholangitis. A trichrome stain shows minimal periportal fibrosis.
Differential diagnosis
Board review style question #1
    Which of the two following features are considered pathognomonic for primary biliary cholangitis?

  1. Antimitochondrial antibody and florid duct lesions
  2. Antineutrophil cytoplasmic antibody and onion skin fibrosis
  3. Antinuclear antibody and ductular reaction
  4. Antismooth muscle antibody and interface hepatitis
Board review answer #1
A. Antimitochondrial antibody and florid duct lesions

Reference: Primary biliary cholangitis

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Board review style question #2

    A middle aged woman presents with jaundice and pruritis. Lab testing reveals elevated liver enzymes and alkaline phosphatase. A liver biopsy shows the above finding. Which of the following therapies should be offered first?

  1. Liver transplant
  2. Low dose steroids
  3. Sofosbuvir
  4. Ursodeoxycholic acid
Board review answer #2
D. Ursodeoxycholic acid. This is primary biliary cholangitis.

Reference: Primary biliary cholangitis

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