Liver & intrahepatic bile ducts

Noninfectious hepatitis

Granulomatous hepatitis

Last staff update: 3 March 2023 (update in progress)

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PubMed Search: Granulomatous hepatitis

Anthony W.H. Chan, M.B.Ch.B.
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Cite this page: Chan AWH. Granulomatous hepatitis. website. Accessed March 24th, 2023.
Definition / general
  • Liver disease characterized by the presence of granulomas in the liver
Essential features
  • Liver disease characterized by the presence of granulomas in the liver
  • There are different etiologies, which may be associated with different subtypes of granulomas
ICD coding
  • ICD-10: K75.3 - granulomatous hepatitis, not elsewhere classified
Clinical features
  • Clinical manifestations depend on the underlying etiology
  • Identification of the presence of granulomas in the liver histologically
  • Clinical, radiological and microbiological correlations are required to reveal the underlying etiology
Case reports
Microscopic (histologic) description
  • Morphology (epithelioid, suppurative, fibrin ring or lipogranuloma) may suggest underlying etiology
  • Epithelioid granuloma: infectious and noninfectious (e.g., primary biliary cholangitis, drug induced liver injury, foreign body reaction, sarcoidosis, Crohn's disease, chronic granulomatous disease, lymphoma)
  • Caseating epithelioid granuloma: typically associated with infections, most notably tuberculosis
  • Suppurative granuloma (granulomatous inflammation with stellate abscess formation or suppurative inflammation): bartonellosis, yersinosis, tularemia, listerosis, melioidosis, actinomycosis and fungal infection
  • Fibrin ring granuloma (also known as doughnut granuloma; central fat globule surrounded by a circumferential rim of fibrin and histiocytes): originally pathognomonic for Q fever (Coxiella burnetii); now considered as nonspecific and could be associated with mycobacterial infection, staphylococcal bacteremia, leishmaniasis, toxoplasmosis, cytomegalovirus, Epstein-Barr virus, acute hepatitis A, systemic lupus erythematosus, allopurinol toxicity and lymphoma
  • Lipogranuloma (central fat globule surrounded by histiocytes without a fibrin ring): alcoholic and nonalcoholic fatty liver disease, mineral oil
Microscopic (histologic) images

Contributed by Anthony W.H. Chan, M.B.Ch.B.

Fibrin ring granuloma

Classical Hodgkin lymphoma

Trifluoperazine induced liver injury

PBC associated portal granuloma PBC associated portal granuloma

PBC associated portal granuloma

Hepatic granuloma in sarcoidosis

Hepatic granuloma in sarcoidosis

Lipogranuloma in NAFLD Lipogranuloma in NAFLD

Lipogranuloma in NAFLD

Sample pathology report
  • Liver, right lobe, biopsy:
    • Granulomatous hepatitis without significant fibrosis (see comment)
    • Comment: The biopsy showed lobular necroinflammatory activity and scattered noncaseating epithelioid granulomas. Infectious and noninfectious causes need to be considered. From the clinical history, the patient received a course of Augmentin for his upper respiratory tract infection before he was admitted for jaundice. Augmentin is one of the known offensive agents associated with drug induced granulomatous hepatitis. Clinical follow up and monitoring of his liver function are recommended. Although histochemical stains for infectious agents (Gram, Grocott, PAS, PASD and Ziehl-Neelsen) do not reveal any specific organism, correlation with microbiological investigation is still recommended to exclude any infection.
Board review style question #1
Which disease is classically associated with fibrin ring granulomas in the liver?

  1. Familial Mediterranean fever
  2. Q fever
  3. Scarlet fever
  4. Viral hemorrhagic fever
Board review style answer #1
Board review style question #2

Which histochemical stain is useful to differentiate between lipogranuloma and the granuloma seen in Q fever?

  1. Mucicarmine
  2. Periodic acid-Schiff diastase (PASD)
  3. Phosphotungstic acid hematoxylin (PTAH)
  4. Ziehl-Neelsen (ZN)
Board review style answer #2
C. Phosphotungstic acid hematoxylin (PTAH) is useful to highlight a thin rim of fibrin surrounding the central fat globule of the fibrin ring granuloma

Comment Here

Reference: Granulomatous hepatitis
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