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Hepatitis E virus infection
Other Resources UpToDate PubMed

Hepatitis E virus infection

Contributors: Ricardo A. Franco MD, Mukesh Patel MD
Other Resources UpToDate PubMed


Hepatitis E is an acute, self-limited hepatitis caused by hepatitis E virus (HEV). Although the disease is rarely diagnosed in industrialized countries, including the United States, hepatitis E is the most likely cause of acute hepatitis in adults worldwide and is highly endemic in Southeast Asia. On the basis of viral genetic and epidemiological features, the disease is divided into two forms, epidemic and autochthonous:
  1. Outbreaks and sporadic cases of epidemic hepatitis E are common in developing countries and are caused by HEV genotypes 1 and 2. The epidemic form is associated with waterborne and fecal-oral transmission, with humans as the exclusive hosts. The epidemic form is rarely imported to the United States via travel.
  2. In contrast, autochthonous hepatitis E is caused by genotypes 3 and 4, and pigs are the natural reservoir. Sporadic cases occur in developed countries when humans become accidental hosts. Rarely, transfusion-related HEV infection has occurred.
Acute hepatitis E may be asymptomatic, marked only by a rise in AST or ALT levels, or symptomatic (with or without jaundice). Asymptomatic infections are likely 10-30 times more common than symptomatic infections. Rare cases may have a subfulminant or fulminant course. Acute infection can be protracted and cholestatic, lasting for several weeks. Fulminant hepatic failure, defined as severe liver failure in the presence of encephalopathy that develops within 8 weeks of the onset of symptoms, is characterized by severe sudden liver cell dysfunction leading to encephalopathy, ascites, and coagulopathy in people with no underlying liver disease. Pregnant individuals are at increased risk for severe illness from HEV infection.


B17.2 – Acute hepatitis E

7111000119109 – Viral hepatitis type E

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Differential Diagnosis & Pitfalls

Hepatitis E cannot be differentiated from other types of viral hepatitis (Hepatitis A virus infection, Hepatitis B virus infection, Hepatitis C virus infection, Hepatitis D virus infection) on the basis of clinical presentation. Moreover, a number of diverse disorders enter into the differential diagnosis of "acute hepatitis." These include:
  • Cytomegalovirus infection
  • Epstein-Barr virus infection
  • Herpes simplex virus
  • Varicella
  • Coxsackie viral infection
  • Toxoplasmosis
  • Histoplasmosis
  • Leptospirosis
  • Alcoholic hepatitis – Serum AST levels rarely rise above 300 units/L, and typically serum AST levels exceed serum ALT levels.
  • Drug-induced hepatotoxicity – Careful medication history should be obtained.
  • Ischemic hepatitis ("shock liver") – Usually in the setting of cardiogenic or septic shock (see Bacterial sepsis).
  • Severe Autoimmune hepatitis – Young females; positive auto-antibodies and other systemic auto-immune manifestations.
  • Acute Budd-Chiari syndrome – Associated primarily with aminotransferase elevations, not alkaline phosphatase, and increased lactate dehydrogenase levels.
  • Wilson disease – This metabolic disorder rarely mimics acute viral hepatitis. Look for Kayser-Fleischer rings and history of psychiatric disorder.
  • Acute fatty liver of pregnancy – It is potentially fatal and most common in third trimester. Liver biopsy shows characteristic steatosis.
  • The syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome) – Common in third trimester; presents with eclampsia, right upper quadrant pain, hypertension, and edema.

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Last Updated:08/05/2021
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Hepatitis E virus infection
A medical illustration showing key findings of Hepatitis E virus infection (Acute) : Abdominal pain, Diarrhea, Fever, Hepatomegaly, Jaundice, ALT elevated, AST elevated, Malaise, Hyperbilirubinemia, Anorexia
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