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

Author: Komal Arora, M.D. (see Authors page)

Revised: 14 November 2017, last major update May 2012

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PubMed Search: Primary biliary cirrhosis[TI] liver[TI] free full text[sb]

Cite this page: Arora, K. Primary biliary cirrhosis. PathologyOutlines.com website. http://pathologyoutlines.com/topic/liverPBC.html. Accessed December 16th, 2017.
Definition / general
  • Chronic, progressive, often fatal cholestatic liver disease with destruction of small, intrahepatic bile ducts, portal inflammation and scarring leading to cirrhosis and liver failure
  • Possibly autoimmune; associated with Sj√∂gren syndrome, scleroderma, thyroiditis, rheumatoid arthritis, Raynaud phenomenon, membranous glomerulonephritis, systemic lupus erythematosus, celiac disease
  • Involves most proximal portion of biliary tree, the small bile ducts and canals of Hering; larger bile ducts affected only irregularly (Hum Pathol 2002;33:983)
  • 85% women, usually ages 40 - 60
  • Symptoms: insidious onset of pruritis, malaise, dark urine, light stools, hepatomegaly, xanthomas, xanthelasma
  • Death due to liver failure, hemorrhage of varices, infection
Staging / staging classifications
  1. Florid duct lesion; portal inflammation with damage to septal or interlobular bile ducts but without expansion of portal tracts or piecemeal necrosis
  2. Expansion of portal tracts with piecemeal necrosis and ductular proliferation but no bridging
  3. Decreased inflammation but fibrous septum formation with bridging necrosis or fibrosis
  4. Cirrhosis
Laboratory
  • Elevated serum alkaline phosphatase and cholesterol, IgM antimitochondrial autoantibodies in 95%, elevated conjugated bilirubin (late)
  • Note: if negative antimitochondrial antibody (occurs in 5%), must have a cholangiogram to rule out primary sclerosing cholangitis
  • Note: M2 form of antimitochondrial antibody, present in 90%, is against E2 subunit of pyruvate dehydrogenase complex dihydrolipoamide acetyltransferase on inner face of inner mitochondrial membrane, causes hypocomplementemia and formation of immune complexes
  • Antimitochondrial antibodies are most important diagnostic marker; has coarse granular cytoplasmic staining of distal renal tubules and parietal cells (rodent stomach / kidney blocks) with indirect immunofluorescence
  • Note: anti liver kidney microsomal antibody does NOT stain distal renal tubules
  • NOMA: natural occurring mitochondrial Ab; found in close contacts of PBC patients, even lab techs processing sera from these patients; antibodies to M2 and M9 but different epitopes; significance uncertain, raises question of infectious etiology
Treatment
  • Liver transplant
Gross description
  • Liver eventually turns green; capsule initially smooth, then granular, then micronodular
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
  • Florid duct lesion: interlobular bile ducts (those that course alongside the hepatic artery) are destroyed by poorly formed portal epithelioid granulomas, lymphocytes, plasma cells and macrophages
  • Obstruction to bile flow causes progressive hepatic damage (periportal granulomas are relatively specific)
  • Upstream portal tracts have bile ductular proliferation, inflammation and necrosis of hepatic parenchyma; eventually causes portal tract scarring and bridging fibrosis
Microscopic (histologic) images

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Chronic inflammatory infiltrate and loss of bile ducts

Epithelial damage with granulomas and lymphocytic inflammation

Positive stains
  • Copper (indicates chronic cholestatic condition)