Hepatitis E Virus

1. HEPATITIS E VIRUS
BY- SANJU SAH
St. Xavier’s college, Maitighar, Kathmandu

3. Background
• Hepatitis E virus is the most common cause of epidemic worldwide.
• HEV is endemic in most equatorial countries, leading to sporadic
outbreaks.
• The infection was first reported from the Indian subcontinent and
subsequently from other parts of Asia, the Middle East, Central and
South America, Africa, Central Europe and Russia.
• The largest known outbreak occurred in Xinjiang, China, between
1986 and 1988, affecting almost 120,000 individuals.

4. Introduction
• Hepatitis E virus is a non-enveloped, spherical particle
and has an icosahederal symmetry.
• It is approximately 30 to 34 nm in diameter.
• The virus is resistant to chloroform and heating at 56 °
C for 1 hour.
• It is susceptible to boiling for 5 min and to
chlorination.
• There are at least four genotypes of the virus,
genotypes 1 ,2,3 and 4.

5. Fig 1: Morphology of HEV particles demonstrated by electron
microscopy.

6. Genome
• The HEV genome is a single stranded positive sense RNA,
with a 7-methylguanine cap at its 5’ end and a poly (A) at
its 3’ end.
• The genome contains three partially overlapping open
reading frames.
• ORF 1 encodes a relatively large polyprotein that contains
consensus motifs for a methyltransferase, a papain-like
cysteine protease, a helicase and an RNA-dependent RNA
polymerase similar to those found in the alphaviruses.

7. • ORF 2 encodes a 72 kDa capsid polypeptide and
contains a signal peptide sequence and three
potential glycosylation sites.
• Overlapping ORF1 and ORF2 is a small ORF 3 that
encodes a 13 kDa, cysteine-rich polypeptide that is
immunoreactive with many patient sera.

8. Fig 2: Genomic structure of HEV

9. Replication

10. 1. The virus binds with a specific yet uncharacterized
receptor.
2. The virus then uncoats to release genomic RNA that is
translated in the cytoplasm into nonstructural
proteins.
3. RNA-dependent RNA polymerases replicate the
positive-sense genomic RNA into negative-sense
transcripts;the latter then act as templates for the
synthesis of a sub-genomic RNA as well as full length
positive sense transcripts.

11. 4. The positive-sense subgenomic RNA is then translated into
ORF2 and ORF3 proteins.
5. The ORF2 protein packages the genomic RNA to assemble new
virions, while the ORF3 protein may optimize the host cell
environment for viral replication.
6. The ORF3 protein is also associated with endomembranes or
plasma membranes and may aid in viral egress.
7. Recent studies suggest that mature virions excreted from the
liver into the circulation are subsequently removed through a
process that is not understood at present, to resume a fresh
infection cycle.

12. Pathogenesis
• There is an incubation period of 2–6 weeks, whichprecedes
the development of raised liver enzymes.
• During this period there are viremia and fecal excretion of
virus, reflecting replication of virus within hepatocytes.
• Antibodies to HEV develop just before elevations of liver
enzymes.
• Anti- HEV IgM titres increase rapidly and then wane overthe
weeks following infection, while anti-HEV IgG antibodytitres
continue to rise more gradually during the convalescence
period, and detectable anti-HEV IgG may persist for months
to years.

13. Fig 3: Clinical, biochemical and serological profile of hepatitis E virus
infection.

14. Clinical manifestations
• HEV, like HAV, causes an acute disease that does not progress to a chronic
phase and is indistinguishable from other viral hepatitis
• The prodromal symptoms of infection include anorexia,abdominal
discomfort, nausea, myalgia, malaise, fever and occasionally joint pains
accompanied with jaundice, dark urine and pale stools, and tenderness in
the right upper quadrant of the abdomen.
• The infection is self-limiting, but fulminant hepatitis with a high mortality
rate occurs in infected pregnant women.
• HEV-related acute liver failure (ALF) in pregnancy is an explosive disease
with rapid progression of symptoms: high occurrence of cerebral oedema,
sepsis and disseminated intravascular coagulation.

15. The main differences are :
• the incubation period is rather longer (about 6 weeks)
• infection is generally acquired in adolescence or
adulthood, rather than in infancy. Person to person
transmission rates are low
• in women becoming infected during the later stages of
pregnancy the mortality rate is approximately 20
percent
• fulminant disease is more common than in HAV
infections.

16. Laboratory diagnosis

17. Treatment
• There is no specific treatment, treatment is
supportive.
• If fulminant hepatitis develops, liver
transplantation may be indicated

18. Prevention and control
• The one currently licensed hepatitis E vaccine (HEV
239 vaccine, Hecolin) is considered a promising
vaccine which has shown a high degree of efficacy
against hepatitis E disease
• Provision of safe drinking water and the sanitary
disposal of human waste