A short review on Hepatitis E virus and HEV disease.

1. HEPATITIS E VIRUS An Overview
Presented By
Dr. Amit Paul
MBBS, DMU,
PGT
MPH (ON
COURSE)

2. HEPATITIS E VIRUS
• Hepatitis E virus causes viral Hepatitis E
disease.
• It is one of five known hepatitis viruses; A, B,
C, D and E.

3. HEPATITIS E VIRUS
• The virus has at least 4 different types:
genotypes 1, 2, 3 and 4.
• Genotypes 1 and 2 have been found only in
humans.
• Genotypes 3 and 4 circulate in several animals
including pigs, wild boars and deer without
causing any disease, and occasionally infect
humans.

4. HISTORICAL BACKGROUND
• Infection with this virus was first
documented in 1955 during an outbreak in
New Delhi, India.
• Several waterborne outbreaks were reported
throughout India, and most of these case
were non-A and non-B, leading the disease to
be described as enteric non-A, non-B
hepatitis(ENANBH)

5. HISTORICAL BACKGROUND
• A major water related epidemic outbreak in
the Kashmir valley was reported at ends of
1978, with 52,000 cases and 1,700 deaths.
• 1990, this novel ENANBH was partially
cloned and sequence and was henceforth
called the hepatitis E virus(HEV)

6. EPIDEMIOLOGICAL PREVALENCE
• Every year there are an estimated 20 million
HEV infections worldwide, leading to an
estimated 3.3 million symptomatic cases of
hepatitis E.
• WHO estimates that hepatitis E caused
approximately 44 000 deaths in 2015

7. GEOGRAPHICAL SCENARIO

8. GEOGRAPHICAL SCENARIO
• Hepatitis E is found worldwide, but hepatitis
E is most common in developing countries
with inadequate water supply and poor
environmental sanitation.
• Hepatitis E epidemics involving large
numbers of people have been reported in
Asia, the Middle East, Africa, and Central
America

9. BANGLADESH SITUATION
• Hepatitis E genotype 1 is most prominent in
our region.
• According to the study, Hepatitis E virus is a
major (34%) cause of acute jaundice in
tertiary hospitals in Bangladesh.
• Three-quarters of the acute hepatitis E
cases were male, and HEV infection was
higher among patients residing in urban
areas than patients in rural areas (41% vs
32%)

10. STRUCTURE OF
HEPATITIS E VIRUS
• HEV is a small, non-enveloped, icosahedral
virus with a diameter of approximately 32-34
nm.
• The capsid of the virus seems to be
composed of a single capsid protein. The
HEV genome is a single-stranded, positive-
sense RNA molecule with a size of
approximately 7.2 kb

11. STRUCTURE OF
HEPATITIS E VIRUS
• Hepatitis E virus (HEV) is a non-enveloped
single-stranded RNA virus. It has been
classified as the single member of the genus
hepevirus in the family Hepeviridae.

12. VIROLOGY
• Viral replication starts with the translation of the ORF1 encoded non
structural polyprotein.
• An RNA dependent RNA polymerase then transcribes the full length
negative sense RNA.
• This RNA serves as a template for the synthesis of two viral positive
sense RNAs in infected cells, a full length genomic RNA and a
subgenomic RNA containing the capsid protein encoding ORF2 and
polyfunctional protein encoding ORF3.

13. PATHOGENESIS
• The pathogenesis of hepatitis E is poorly
understood. Since HEV is presumably transmitted
by the fecal-oral route, it is unclear how the virus
reaches the liver. Perhaps there is an extra-hepatic
site of virus replication. The virus could replicate in
the intestinal tract before reaching the liver..

14. PATHOGENESIS
• Negative strands of HEV RNA, indicating virus
replication, have been detected in the small
intestine, lymph nodes, colon, and liver of pigs,
indicating extra-hepatic HEV replication
• HEV then replicates in the cytoplasm of
hepatocytes and is released into both blood and
bile. The liver damage induced by HEV infection
may be immune-mediated by cytotoxic T cells and
natural killer (NK) cells since HEV is not cytopathic
The virus is shed in the stool.

15. ROUTE OF TRANSMISSION
• Genotype 1 & Genotype 2: Waterborne (fecal
contaminated water); human to human;
maternofetal; probably zoonotic (genotype 1)
• Genotype 3 & Genotype 4: Zoonotic: mainly via
consumption of raw or undercooked contaminated
animal meat; environmental (shellfish); to date
environmental shellfish has been reported
exclusively for genotype 3.

16. CLINICAL FEATURES OF HEV
• Most HEV infection have clinically ‘silent’ course.
• Incubation Period: 3 to 8 weeks
• Prodromal phase: Short
• Symptoms or jaundice: Days to severel weeks
• Most cases ar self-limited.
• Case fatality rate: 0 to 10%
20% in pregnant women.

17. SIGNS AND SYMPTOMS
• An initial phase of mild fever
• Reduced appetite (anorexia)
• Nausea and vomiting lasting for a few days;
• Abdominal pain, itching , skin rash, or joint pain;
• Jaundice (yellow color of the skin), dark urine and
pale stools; and
• A slightly enlarged, tender liver (hepatomegaly).

18. SIGNS AND SYMPTOMS
• ***These symptoms are often indistinguishable
from those experienced during other liver illnesses
and typically last 1–6 weeks.
• ***These symptoms are often indistinguishable
from those experienced during other liver illnesses
and typically last 1–6 weeks.

19. SIGNS AND SYMPTOMS
• . In rare cases, acute hepatitis E can be severe
and result in fulminant hepatitis (acute liver
failure). These patients are at risk of death.
Pregnant women with hepatitis E, particularly
those in the second or third trimester, are at
increased risk of acute liver failure, fetal loss
and mortality. Up to 20–25% of pregnant women
can die if they get hepatitis E in third trimester.

20. SIGNS AND SYMPTOMS
• Cases of chronic hepatitis E infection have been
reported in immunosuppressed people, particularly
organ transplant recipients on immunosuppressive
drugs, with genotype 3 or 4 HEV infection. These
remain uncommon

21. Laboratory Diagnosis
• Direct Virus Detection
• Detection of HEV Genome by RT-PCR
• Serologic Test Systems for the Detection of HEV
Infection by ELISA and Immuneblot.

22. Laboratory Diagnosis
• Determination of HEV Antigens
• Definitive diagnosis of hepatitis E infection is
usually based on the detection of specific anti-HEV
immunoglobulin M (IgM) antibodies to the virus in a
person’s blood;

23. HEV: TYPICAL SEROLOGIC
COURSE

24. TREATMENT
• There is no specific treatment capable of altering
the course of acute hepatitis E. As the disease is
usually self-limiting, hospitalization is generally not
required. Most important is the avoidance of
unnecessary medications. Acetaminophen,
paracetamol and medication against vomiting
should be used sparingly or avoided.

25. TREATMENT
• Hospitalization is required for people with
fulminant hepatitis and should also be considered
for symptomatic pregnant women.
• Immunosuppressed people with chronic hepatitis E
benefit from specific treatment using ribavirin, an
antiviral drug. In some specific situations,
interferon has also been used successfully.

26. 💉 VACCINE
• Both the rHEV and HEV 239 vaccines have
undergone clinical evaluation and HEV 239 was
licensed and then launched in China in 2012. But
not approved by FDA(USA).

27. PREVENTIONS
• Prevention is the most effective approach against
the infection. At the population level, transmission
of HEV and hepatitis E infection can be reduced by:
• maintaining quality standards for public water
supplies; and
• establishing proper disposal systems for human
faeces.

28. PREVENTIONS
• On an individual level, infection risk can be reduced
by:
• maintaining hygienic practices; and
• avoiding consumption of water and ice of unknown
purity.

29. PREVENTION

30. WHO RESPONSES
• WHO has issued the technical report Waterborne
outbreaks of hepatitis E.
1.recognition,
2.investigation and
3.control.
• The manual gives information about the
epidemiology, clinical manifestations and diagnosis
of hepatitis E. It also provides guidance for public
health authorities on how to respond to outbreaks
of hepatitis E infection.

31. WHO RESPONSES
• To support countries in achieving the global
hepatitis elimination targets under the Sustainable
Development Agenda 2030, WHO is working to:
1. Raise awareness, promote partnerships and
mobilize resources;
2. Formulate evidence-based policy and data for
action;
3. Increase health equities within the hepatitis
response;
4. Prevent transmission; and
5. Scale up screening, care and treatment services.

32. WORLD HEPATITIS DAY

33. REFERENCES
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997574/
• file:///C:/Users/user/OneDrive/Desktop/HEPA%20E%20VIRUS/Trans
mission,%20diagnosis,%20and%20management%20of%20hepatitis%
20E_%20an%20update.html
• https://www.who.int/news-room/fact-sheets/detail/hepatitis-e