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Surgical Pathology Criteria

Graft versus Host Disease (GVHD) of the Liver


  • Attack by engrafted hematopoietic cells and their progeny on the host liver

Diagnostic Criteria

  • Early phase
    • Lymphoplasmacytic infiltration of portal tracts
    • Damage to bile duct epithelium
      • Cytoplasmic swelling and vacuolation
      • Enlarged and overlapping nuclei (reactive epithelial atypia)
      • Apoptosis
  • Late phase
    • Loss of bile ducts
    • Increased fibrosis

Neeraja Kambham MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting : May 9, 2007

Supplemental studies


  • Useful for detection of hepatitis B and other viral diseases

Differential Diagnosis

Chronic viral hepatitis C

  • Dense lymphoid aggregates
  • Interface hepatitis
  • Acidophil bodies

Drug induced damage

  • Chemoirradiation effects last 3-4 weeks
  • Other drugs can have hepatitis or cholestatic picture or granulomas

Primary biliary cirrhosis

  • Can be difficult to distinguish from GVHD
  • Features favoring PBC
    • Granulomas if present
    • Florid bile duct lesions

Venocclusive disease

  • Due to chemotherapy and radiation toxicity
  • Usually presents 3 weeks after therapy
  • Endothelial injury in sinusoids and venules
  • May have fibrin thrombi


  • Acute vs. chronic GVHD: clinically 100 day cutoff
    • Poor correlation between pathologic features and clinical definition of acute vs. chronic
  • Acute GVHD
    • Develops 2-6 weeks after allogeneic transplant
    • Primary targets
      • Skin 90%
      • Liver 40-60%
      • GI tract 30-50%
    • Early recognition of GVHD and prompt intervention improves outcome
    • Advanced GVHD easy to diagnose but mortality can be 50%
  • Chronic GVHD
    • Resembles autoimmune connective tissue disorders
    • Mortality is high due to infections promoted by GVHD associated immunodeficiency
    • Target organs more widespread but skin, liver and GI tract play a major role
  • In liver typically presents as obstructive jaundice due to destruction of small intrahepatic bile ducts, similar to primary biliary cirrhosis


Grade Bile ducts showing epithelial damage
I <25%
II 25-49%
III 50-74%
IV 75-100%
(Not widely performed)


Principal sites of graft versus host disease


  • Shulman HM, Kleiner D, Lee SJ, Morton T, Pavletic SZ, Farmer E, Moresi JM, Greenson J, Janin A, Martin PJ, McDonald G, Flowers ME, Turner M, Atkinson J, Lefkowitch J, Washington MK, Prieto VG, Kim SK, Argenyi Z, Diwan AH, Rashid A, Hiatt K, Couriel D, Schultz K, Hymes S, Vogelsang GB. Histopathologic diagnosis of chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. Pathology Working Group Report. Biol Blood Marrow Transplant. 2006 Jan;12(1):31-47.
  • Heymer B. Clinical and diagnostic pathology of graft versus host disease. Springer Verlag, 2002.
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