Liver and intrahepatic bile ducts - nontumor
Viral hepatitis
Herpes simplex virus hepatitis

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

Topic Completed: 20 May 2019

Revised: 20 May 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: Herpes simplex virus hepatitis[TIAB]

Raul S. Gonzalez, M.D.
Page views in 2018: 1,136
Page views in 2019 to date: 571
Cite this page: Gonzalez R. Herpes simplex virus hepatitis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/liverherpeshep.html. Accessed June 24th, 2019.
Definition / general
  • Rare complication of herpes infection resulting in geographic (nonzonal) hemorrhagic necrosis that is usually fatal
  • 1% of acute liver failure (Clin Transplant 2009;23:37)
Essential features
  • Geographic (nonzonal) hemorrhagic necrosis
  • Usually pregnant women or immunocompromised patients
  • Often clinically unsuspected (Liver Transpl 2007;13:1428)
  • Often not diagnosed until autopsy due to nonspecific clinical features
Epidemiology
  • Immunocompromised patients are most susceptible
  • Immunocompetent patients can be affected (Am J Clin Pathol 1986;85:694)
  • Risk factors include malignancy and pregnancy (mean 31 weeks) (Hum Pathol 1992;23:183)
  • Neonates can also acquire herpes congenitally (as it is one of the TORCH infections), with roughly a quarter of them at risk for developing fulminant hepatitis
Sites
  • Liver
Etiology
  • HSV1 or HSV2
Clinical features
Diagnosis
  • HSV DNA can be detected in the blood
  • 58% diagnosed at autopsy via histologic and immunohistochemical analysis of liver tissue (Liver Transpl 2007;13:1428)
Laboratory
  • Marked elevation of liver serum markers (AST, ALT, bilirubin, alkaline phosphatase, GGT)
  • Leukopenia
  • HSV DNA identified via PCR
Radiology images

Images hosted on other servers:
Missing Image

No liver abnormalities

Missing Image

Lesions mimicking abscess

Prognostic factors
  • Rapid downhill course with acute liver failure, usually fatal (up to 81% of adults) due to massive hepatic necrosis (Clin Transplant 2009;23:37), even with rapid antiviral therapy or liver transplantation (Liver Transpl 2008;14:1498)
  • Better survival after transplantation in children (69%) than adults (38%) (J Hepatol 2011;55:1222)
  • Worse prognosis (Liver Transpl 2008;14:1498): male gender
    • Age > 40 years
    • Immunocompromised
    • ALT > 5,000 U/L
    • Platelet count < 75 x 103/L
    • Coagulopathy
    • Encephalopathy
    • Absence of antiviral therapy
Case reports
Treatment
  • Empiric antiviral therapy (acyclovir)
  • Liver transplantation with lifelong acyclovir prophylaxis
Gross images

Images hosted on other servers:
Missing Image

Random lobular geographic necrosis

Missing Image

Soft nodules

Microscopic (histologic) description
  • Geographic (nonzonal) hemorrhagic necrosis
  • Viable and nonviable areas distributed in a patchy, seemingly random fashion, sometimes with a clean separating border
  • Classic nuclear features of herpes infection (margination, multinucleation, molding) are seen in hepatocytes, though multinucleation is not always observed
Microscopic (histologic) images

Contributed by Yubo "Mike" Wu, D.O.
Missing Image

Low-power necrosis

Missing Image Missing Image

Necrosis

Missing Image Missing Image

Viral cytopathic effect

Missing Image

HSV immunostain

Positive stains
  • HSV
Sample pathology report
  • Autopsy:
    • Widespread liver necrosis consistent with herpetic hepatitis (see comment)
    • Comment: Geographic (nonzonal) hemorrhagic necrosis of the liver is present, along with viral cytopathic effect in surviving hepatocytes. Immunohistochemistry for HSV1 is positive, confirming the diagnosis.
Differential diagnosis
  • The differential diagnosis includes other causes of hepatic necrosis and other causes of viral cytopathic effect:
    • Hypoperfusion (e.g., due to hypovolemic shock)
      • Can cause zone 3 necrosis
    • Medications that cause hepatic necrosis
      • Acetaminophen causes zone 3 necrosis
      • Unusual substances may primarily induce necrosis in other zones
    • Viral hemorrhagic fever (e.g., yellow fever)
      • Can cause zone 2 necrosis, possibly also with zone 2 necrosis
    • Disseminated intravascular coagulation and eclampsia
      • May cause zone 1 necrosis
    • Cytomegalovirus
      • Can cause prominent "owl's-eye" inclusions in hepatocytes, endothelial cells and biliary epithelium
      • Easier to detect in immunocompromised patients
      • Fulminant hepatic failure is not the typical presentation but can occur
    • Adenovirus
      • Close histologic mimicker of hepatic hepatitis
      • Causes random zones of necrosis and viral cytopathic effect
      • Involved hepatocytes have a basophilic, smudgy nucleus without any multinucleation
      • Immunohistochemistry for adenovirus can distinguish adenovirus from herpes
    • Herpes zoster virus
      • Can cause same histologic picture in liver
      • Generally only occurs in immunocompromised patients
      • HSV immunostain is negative, but VZV staining is positive
    • Measles
      • May cause multinucleation without margination or molding
      • Eosinophilic cytoplasmic inclusions may be detected
      • Necrosis would be spotty
Board review question #1
    Herpes simplex hepatitis causes necrosis of hepatocytes in what pattern?

  1. Nonzonal necrosis
  2. Zone 1 necrosis
  3. Zone 2 necrosis
  4. Zone 3 necrosis
Board review answer #1
A. Nonzonal necrosis

Comment Here

Reference: Herpes simplex virus hepatitis
Back to top