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Liver & intrahepatic bile ducts

Viral hepatitis

Herpes simplex virus hepatitis

Author: Raul S. Gonzalez, M.D.

Editor-in-Chief: Debra L. Zynger, M.D.

Last author update: 10 December 2020

Last staff update: 29 July 2022

Copyright: 2019-2024, PathologyOutlines.com, Inc.

PubMed Search: Herpes simplex virus hepatitis

Table of Contents

Cite this page: Gonzalez R. Herpes simplex virus hepatitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverherpeshep.html. Accessed December 23rd, 2024.

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

Uncommon cause of liver failure in adults (Liver Transpl 2008;14:1498)
Anicteric (not accompanied by jaundice)
Fever (98%), coagulopathy (84%) and encephalopathy (80%) (Liver Transpl 2008;14:1498)
Clinical presentation in adults is typically that of shock

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:

No liver abnormalities

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

11 day old boy successfully treated without transplantation (ACG Case Rep J 2017;4:e23)
18 year old women with fever and pharyngodynia (Case Reports Hepatol 2017;2017:4630621)
41 year old women at 31 weeks of pregnancy with fatal course (Intractable Rare Dis Res 2017;6:124)
44 year old woman with nausea and vomiting (Case of the Month #481)
67 year old man with lesions mimicking abscess (Case Reports Hepatol 2016;2016:8348172)
89 year old man with sepsis secondary to urinary tract infection and fatal course (Eur J Case Rep Intern Med 2018;5:000982)

Treatment

Empiric antiviral therapy (acyclovir)
Liver transplantation with lifelong acyclovir prophylaxis

Gross images

Images hosted on other servers:

Random lobular geographic necrosis

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.

Low-power necrosis

Necrosis

Viral cytopathic effect

HSV immunostain

Positive stains

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 style question #1

Nonzonal necrosis
Zone 1 necrosis
Zone 2 necrosis
Zone 3 necrosis

Board review style answer #1

A. Nonzonal necrosis

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Reference: Herpes simplex virus hepatitis