Liver & intrahepatic bile ducts

Viral hepatitis

Adenovirus hepatitis

Last author update: 10 January 2023
Last staff update: 10 January 2023

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PubMed Search: Adenovirus hepatitis

Vladyslav Ilchenko, M.D.
Rifat Mannan, M.B.B.S., M.D.
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Cite this page: Ilchenko V, Mannan R. Adenovirus hepatitis. website. Accessed February 22nd, 2024.
Definition / general
  • Adenoviruses are widely distributed viruses that usually cause self limited infections; but in an immunocompromised host they can cause severe infections with injuries to multiple organs, including the liver
  • While severe acute liver failure due to adenovirus infection is rare, it is characterized by rapid progression and is frequently fatal
  • Such cases were reported in patients after allogeneic hematopoietic stem cell transplantation (HSCT), liver transplantation, chemotherapy regimens and from other causes (Transpl Infect Dis 2021;23:e13496, Infection 2014;42:105)
  • However, adenovirus hepatitis can also occur in immunocompetent adults (J Investig Med High Impact Case Rep 2022;10:23247096221079192)
Essential features
  • Usually immunocompromised transplant recipients
  • Grossly characterized by the presence of coagulative necrosis in liver parenchyma
  • Diagnosis made on liver biopsy with confirmation by adenovirus immunostaining
ICD coding
  • ICD-10: B97.0 - adenovirus as the cause of diseases classified elsewhere
  • Usually occurs in immunocompromised adults and children
  • More frequent in the patients from these groups (Infection 2014;42:105):
    • Liver transplant recipients
    • Bone marrow transplant recipients
    • Patients on (or after) oncology related chemotherapy regimens
    • Patients with severe combined immunodeficiency
    • HIV infected patients
    • Heart, kidney and other transplant recipients
  • Liver
Clinical features
  • In immunocompetent patients, it causes mild illness with respiratory symptoms, keratoconjunctivitis, gastroenteritis, etc.
  • Fever is the most common presenting symptom (Am J Surg Pathol 2017;41:810)
  • Other nonspecific signs (e.g., abdominal pain, memory and cognitive disorder, convulsions) were reported (Transpl Infect Dis 2021;23:e13496)
  • In immunocompromised patients, severe disease may occur, including fulminant hepatitis
Radiology description
Radiology images

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Liver hypodense areas

Liver hypodense areas

Prognostic factors
  • Rapid progression with massive liver necrosis is usually fatal; patients die secondary to organ failure (Am J Surg Pathol 2017;41:810)
  • Surviving patients had limited necrosis at the time of initial diagnosis; these patients also had only relatively mild peak elevations in their serum AST and ALT (mean: 140 and 133, respectively) (Am J Surg Pathol 2017;41:810)
Case reports
Gross description
Gross images

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Areas of coagulative necrosis

Areas of coagulative necrosis

Microscopic (histologic) description
  • Focal to massive coagulative necrosis in liver without particular zonal distribution (Am J Surg Pathol 2017;41:810)
  • Intranuclear viral inclusions within hepatocytes with smudged or glassy appearance (Am J Surg Pathol 2017;41:810)
  • Viral inclusions within the biliary epithelium (Am J Surg Pathol 2017;41:810)
  • Mild or absent inflammation, portal tract granulomas may be present (Am J Surg Pathol 2017;41:810)
  • Immunostaining for adenovirus demonstrates strong nuclear staining and is used for confirmation of the diagnosis because immunocompromised patients can have herpes simplex, cytomegalovirus and other viral infections
Microscopic (histologic) images

Contributed by Vladyslav Ilchenko, M.D. and Case #354
Coagulative necrosis

Coagulative necrosis

Adenovirus immunohistochemistry

Adenovirus IHC

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Large necrotic focus

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Nuclear inclusion bodies

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Nuclear and cytoplasmic viral inclusion bodies

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Adenovirus immunostain

Positive stains
  • Adenovirus immunohistochemistry (nuclear staining)
Sample pathology report
  • Liver, biopsy:
    • Hepatitic injury pattern with focal coagulative necrosis, consistent with adenovirus hepatitis (positive adenovirus immunohistochemistry); negative for portal fibrosis (see comment)
    • Comment: The patient's clinical history of stem cell transplantation for acute myeloid leukemia and positive serology for adenovirus is noted.
Differential diagnosis
  • Cytomegalovirus hepatitis:
    • Neutrophilic microabscesses may be present
    • Characteristic intranuclear / cytoplasmic inclusions for CMV
    • Positive CMV immunostain, both intranuclear and cytoplasmic
  • Herpes simplex virus hepatitis:
    • Hemorrhagic necrosis may be present
    • Multinucleation of hepatocyte nuclei
    • Positive immunostain is helpful
  • Varicella zoster virus hepatitis:
    • Histologic features are nonspecific
    • Immunostain and PCR can be helpful
  • Drug induced liver injury:
    • May show cholestatic injury pattern
    • Lacks viral inclusions
Board review style question #1
Adenovirus hepatitis Adenovirus hepatitis Adenovirus hepatitis Adenovirus hepatitis

Which of the following denotes classical morphological findings in the liver biopsy from a patient with adenovirus hepatitis?

  1. Hepatocytes with enlarged, smudged nuclei and intranuclear inclusion bodies
  2. Lymphoid aggregates in portal tracts, epithelial damage of small bile ducts
  3. Neutrophilic microabscess
  4. Presence of multinucleated giant cells
  5. Prominent mononuclear infiltrate within portal tracts and sinusoids
Board review style answer #1
A. Hepatocytes with enlarged, smudged nuclei and intranuclear inclusion bodies

Comment Here

Reference: Adenovirus hepatitis
Board review style question #2
What immunohistostaining pattern is typical for liver cells in adenovirus hepatitis?

  1. Cytoplasmic inclusions staining
  2. Diffuse staining of cytoplasm
  3. Partial or complete membrane staining
  4. Strong nuclear staining
Board review style answer #2
E. Strong nuclear staining

Comment Here

Reference: Adenovirus hepatitis
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