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Info


A. Overview

  1. Self limited, enterically transmitted acute viral hepatitis
  2. Occurs as epidemic outbreaks mainly in underdeveloped countries
  3. Fecal-oral (usually contaminated water) transmission
  4. Incubation period after ~40 days
  5. Fatality rate <3% overall; 15-25% in pregnant women
  6. Does not cause chronic hepatitis in normal hosts
  7. Chronic HEV hepatitis reported in organ transplant recipients with immunosuppression [2]
  8. New isolate recently reported in USA [3]

B. Properties of HEV

  1. Icosahedral, nonenveloped positive strand RNA virus
  2. Enterically transmitted non-A, non-B hepatitis, 32-34 nm particles
  3. The HEV genome RNA is 7.5kb and has three open reading frames (ORF)
    1. ORF 1 codes for replication and RNA processing proteins (similar to rubella proteins)
    2. ORF 2 codes for structural proteins (main antigenic determinant)
    3. ORF 3 has unclear function but may be a structural protein
  4. Related to Caliciviridae family (enteric viruses which cause diarrhea in humans)

C. Symptoms and Signs

  1. Typical of acute viral hepatitis
  2. Malaise, Fatigue
  3. Anorexia, nausea, vomiting
  4. Jaundice
  5. Abdominal pain, hepatomegaly
  6. Fever
  7. HEV in Pregnancy
    1. Fulminant hepatic failure - mainly in pregnancy
    2. Preganant women with jaundice caused by acute HEV have higher maternal mortality, worse obstetric outcomes than jaundiced pregnant women with other acute viral hepatidites [4]
  8. In transplant patients with chronic HEV, inflammation with fibrosis persists on liver biopsy [2]
  9. Hepatitis A virus is by far the most common cause of acute viral hepatitis in USA

D. Diagnosis

  1. Liver enzyme (ALT, AST) increases occur with clinical illness, 1-2 months after infection
  2. IgM anti-HEV increases in about 1 month and is nearly undetectable in 4-5 months
  3. IgG anti-HEV increases in 6-8 weeks and remains high for >12 months after infection
  4. Definitive diagnosis of HEV now uses antibody detection in acute serum
    1. First tests used immune electron microscopy for detection
    2. Western blot assays have now been developed for specific detection of antibodies
    3. ELISA or RIAs have now been developed as well
  5. HEV RNA reverse-transcription polymerase chain reaction (RT-PCR) has been developed

E. Treatment and Prevention

  1. No specific therapy; no effective antiviral agents have been identified to date
  2. Supportive care is mainstay
  3. Liver transplantation in cases of fulminant failure (usually not available)
  4. Vaccines are being developed
  5. Immune globulin (from patients in endemic areas) does not appear to provide protection

References

  1. Mast EE and Krawczynski K. 1996. Annu Rev Med. 47:257 abstract
  2. Kamar N, Selves J, Mansuy JM, et al. 2008. NEJM. 358(8):811 abstract
  3. Kwo PY, Schlauder GG, Carpenter HA, et al. 1997. Mayo Clin Proc. 72(12):1133 abstract
  4. Patra S, Kumar A, Trivedi SS, et al. 2007. Ann Intern Med. 147(1):28 abstract