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HEPATITIS E
                 INFECTION
                  Dr.T.V.Rao MD




DR.T.V.RAO MD                     1
WHAT IS VIRAL HEPATITIS E
• Hepatitis E is a viral hepatitis caused by
  infection with a virus called hepatitis E virus
  (HEV). HEV is a positive-sense single-stranded
  RNA icosahedral virus with a 7.5 kilobase
  genome. HEV has a fecal-oral transmission
  route. It is one of five known hepatitis viruses: A,
  B, C, D, and E. Infection with this virus was first
  documented in 1955 during an outbreak in New
  Delhi, India
DR.T.V.RAO MD                                            2
A TRUE STORY OF HEPATITIS E
                INFECTION
• In 1983, Dr. Balayan was investigating an outbreak of non-A,
  non-B hepatitis in a central Asian part of the Soviet Union.
  Though he wanted to bring samples back to his Moscow
  laboratory, he lacked refrigeration. So he made a shake of
  yogurt and an infected patient’s stool, drank it, went back to
  Moscow, and waited. When he became seriously ill a few weeks
  later, he started collecting and analysing his own samples. In
  these he found a new virus that produced liver injury in
  laboratory animals and could be seen by electron microscopy. It
  looked a lot like hepatitis A virus, but he could show that it was
  not, because he already had antibodies against the hepatitis A
  virus and these did not react with the new virus.
• ( National Institute of Allergy and Infectious Diseases )
DR.T.V.RAO MD                                                          3
ROBERT PURCELL, ALBERT KAPIKIAN, AND STEPHEN FEINSTONE
     WITH AN ELECTRON MICROSCOPE. (CREDIT: NIAID)




 DR.T.V.RAO MD                                     4
HEPATITIS E - GENOME
• The genome is approximately 7200 bases in length, is a
  polyadenylated single-strand RNA molecule that contains
  three discontinuous and partially overlapping open
  reading frames (ORFs) along with 5' and 3' cis-acting
  elements, which have important roles in HEV replication
  and transcription. ORF1 encode a methyltransferase,
  protease, helicase and replicase; ORF2 encode the
  capsid protein and ORF3 encodes a protein of undefined
  function. A three-dimensional, atomic-resolution structure
  of the capsid protein in the context of a virus-like particle
  has been described. An in vitro culture system is not yet
  available
 DR.T.V.RAO MD                                                5
Hepatitis E - Clinical Features

     Incubation period:        Average 40 days
                                Range 15-60 days
     Case-fatality rate:   Overall, 1%-3%
                                Pregnant women,
                                15%-25%
     Illness severity:         Increased with age
     Chronic sequelae:         None identified
DR.T.V.RAO MD                                        6
Hepatitis E
                Epidemiologic Features

     Most outbreaks associated with faecally contaminated drinking
      water.
     Several other large epidemics have occurred since in the Indian
      subcontinent and the USSR, China, Africa and Mexico.
     In the United States and other nonendemic areas, where
      outbreaks of hepatitis E have not been documented to occur, a
      low prevalence of anti-HEV (<2%) has been found in healthy
      populations. The source of infection for these persons is unknown.
     Minimal person-to-person transmission.


DR.T.V.RAO MD                                                         7
GEOGRAPHICAL DISTRIBUTION
• Hepatitis E is found worldwide and different
  genotypes of the hepatitis E virus determine
  differences in epidemiology. For example,
  genotype 1 is usually seen in developing
  countries and causes community level outbreaks
  while genotype 3 is usually seen in the
  developed countries and does not cause
  outbreaks

DR.T.V.RAO MD                                  8
DR.T.V.RAO MD   9
DISTRIBUTION OF HEPATITIS E
               INFECTION, 2010




DR.T.V.RAO MD                          10
MORBIDITY AND MORTALITY
• Globally, 70 000
  deaths and 3.4
  million cases of
  acute hepatitis E
  are attributable to
  infection with
     hepatitis E virus
     genotypes 1 and 2.
DR.T.V.RAO MD                11
TRANSMISSION OF INFECTION
• The hepatitis E virus
  is transmitted mainly
  through the faecal-
  oral route due to
  faecal contamination
  of drinking water.
  Other transmission
  routes have been
  identified, which
  include
DR.T.V.RAO MD             12
DR.T.V.RAO MD   13
Prevention and Control Measures for
 Travelers to HEV-Endemic Regions

      Avoid drinking water (and beverages with ice) of
       unknown purity, uncooked shellfish, and uncooked
       fruit/vegetables not peeled or prepared by traveler.
      IG prepared from donors in Western countries does not
       prevent infection.
      Unknown efficacy of IG prepared from donors in
       endemic areas.
      Vaccine?

DR.T.V.RAO MD                                             14
TRANSMISSION
•    Foodborne transmission from ingestion of
     products derived from infected animals;
• Zoonotic transmission from animals to humans;
• Transfusion of infected blood products;
• Vertical transmission from a pregnant woman
  to her foetus.

DR.T.V.RAO MD                                     15
INCUBATION PERIOD
• The incubation period following
  exposure to the hepatitis E virus
  ranges from three to eight
  weeks, with a mean of 40 days.
  The period of communicability is
  unknown.
DR.T.V.RAO MD                         16
SYMPTOMS
• The hepatitis E virus causes acute sporadic
  and epidemic viral hepatitis. Symptomatic
  infection is most common in young adults aged
  15–40 years. Although infection is frequent in
  children, the disease is mostly asymptomatic or
  causes a very mild illness without jaundice
  (anicteric) that goes undiagnosed


DR.T.V.RAO MD                                   17
CLINICAL PRESENTATION
Jaundice
•    anorexia (loss of appetite);
•    an enlarged, tender liver (hepatomegaly);
•    abdominal pain and tenderness;
•    nausea and vomiting;
•    fever.

DR.T.V.RAO MD                                    18
HEPATITIS E INFECTION AND
                   PREGNANCY
• In rare cases, acute hepatitis E can result in
  fulminant hepatitis (acute liver failure) and death.
  Overall population mortality rates from hepatitis
  E range from 0.5% to 4.0%. Fulminant hepatitis
  occurs more frequently during pregnancy.
  Pregnant women are at greater risk of obstetrical
  complications and mortality from hepatitis E,
  which can induce a mortality rate of 20% among
  pregnant women in their third trimester.
DR.T.V.RAO MD                                        19
CHRONIC HEPATITIS E
                    INFECTION
• Cases of chronic
  hepatitis E infection
  have been reported in
  immunosuppressed
  people. Reactivation of
  hepatitis E infection has
  also been reported in
  immunocompromised
  people.


DR.T.V.RAO MD                         20
DIAGNOSIS BY DETECTION OF ANTIBODIES

                     • Diagnosis of
                       hepatitis E
                       infection is
                       therefore usually
                       based on the
                       detection of
                       specific antibodies
                       to the virus in the
DR.T.V.RAO MD
                       blood.            21
NEWER METHODS IN DIAGNOSIS
• Reverse
  transcriptase
  polymerase chain
  reaction (RT-PCR) to
  detect the hepatitis E
  virus RNA;
• Immune electron
  microscopy to detect
  the hepatitis E virus.
DR.T.V.RAO MD                      22
TREATMENT
• There is no available treatment capable of
  altering the course of acute hepatitis. Prevention
  is the most effective approach against the
  disease.
• As hepatitis E is usually self-limiting,
  hospitalization is generally not required.
  However, hospitalization is required for people
  with fulminant hepatitis and should also be
  considered for infected pregnant women.
DR.T.V.RAO MD                                       23
PREVENTION
Maintaining quality
standards for public
water supplies ;
 Establishing proper
disposal systems to
eliminate sanitary
waste.


DR.T.V.RAO MD                24
PREVENTION
• Maintaining hygienic practices such as hand
  washing with safe water, particularly before
  handling food;
• Avoiding drinking water and/or ice of unknown
  purity;
• Avoiding eating uncooked shellfish, and
  uncooked fruits or vegetables that are not
  peeled or that are prepared by people living in or
  travelling in highly endemic countries
DR.T.V.RAO MD                                      25
VACCINATION - UPDATE
• China has
  produced and
  licensed the first
  vaccine to prevent
  hepatitis E virus
  infection, although
  it is not yet
  available globally.

DR.T.V.RAO MD                 26
• Programme Created by Dr.T.V.Rao MD for
       Medical and Paramedical Students in the
                  Developing World
                        • Email
                • doctortvrao@gmail.com



DR.T.V.RAO MD                                    27

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Hepatitis E infection

  • 1. HEPATITIS E INFECTION Dr.T.V.Rao MD DR.T.V.RAO MD 1
  • 2. WHAT IS VIRAL HEPATITIS E • Hepatitis E is a viral hepatitis caused by infection with a virus called hepatitis E virus (HEV). HEV is a positive-sense single-stranded RNA icosahedral virus with a 7.5 kilobase genome. HEV has a fecal-oral transmission route. It is one of five known hepatitis viruses: A, B, C, D, and E. Infection with this virus was first documented in 1955 during an outbreak in New Delhi, India DR.T.V.RAO MD 2
  • 3. A TRUE STORY OF HEPATITIS E INFECTION • In 1983, Dr. Balayan was investigating an outbreak of non-A, non-B hepatitis in a central Asian part of the Soviet Union. Though he wanted to bring samples back to his Moscow laboratory, he lacked refrigeration. So he made a shake of yogurt and an infected patient’s stool, drank it, went back to Moscow, and waited. When he became seriously ill a few weeks later, he started collecting and analysing his own samples. In these he found a new virus that produced liver injury in laboratory animals and could be seen by electron microscopy. It looked a lot like hepatitis A virus, but he could show that it was not, because he already had antibodies against the hepatitis A virus and these did not react with the new virus. • ( National Institute of Allergy and Infectious Diseases ) DR.T.V.RAO MD 3
  • 4. ROBERT PURCELL, ALBERT KAPIKIAN, AND STEPHEN FEINSTONE WITH AN ELECTRON MICROSCOPE. (CREDIT: NIAID) DR.T.V.RAO MD 4
  • 5. HEPATITIS E - GENOME • The genome is approximately 7200 bases in length, is a polyadenylated single-strand RNA molecule that contains three discontinuous and partially overlapping open reading frames (ORFs) along with 5' and 3' cis-acting elements, which have important roles in HEV replication and transcription. ORF1 encode a methyltransferase, protease, helicase and replicase; ORF2 encode the capsid protein and ORF3 encodes a protein of undefined function. A three-dimensional, atomic-resolution structure of the capsid protein in the context of a virus-like particle has been described. An in vitro culture system is not yet available DR.T.V.RAO MD 5
  • 6. Hepatitis E - Clinical Features  Incubation period: Average 40 days Range 15-60 days  Case-fatality rate: Overall, 1%-3% Pregnant women, 15%-25%  Illness severity: Increased with age  Chronic sequelae: None identified DR.T.V.RAO MD 6
  • 7. Hepatitis E Epidemiologic Features  Most outbreaks associated with faecally contaminated drinking water.  Several other large epidemics have occurred since in the Indian subcontinent and the USSR, China, Africa and Mexico.  In the United States and other nonendemic areas, where outbreaks of hepatitis E have not been documented to occur, a low prevalence of anti-HEV (<2%) has been found in healthy populations. The source of infection for these persons is unknown.  Minimal person-to-person transmission. DR.T.V.RAO MD 7
  • 8. GEOGRAPHICAL DISTRIBUTION • Hepatitis E is found worldwide and different genotypes of the hepatitis E virus determine differences in epidemiology. For example, genotype 1 is usually seen in developing countries and causes community level outbreaks while genotype 3 is usually seen in the developed countries and does not cause outbreaks DR.T.V.RAO MD 8
  • 10. DISTRIBUTION OF HEPATITIS E INFECTION, 2010 DR.T.V.RAO MD 10
  • 11. MORBIDITY AND MORTALITY • Globally, 70 000 deaths and 3.4 million cases of acute hepatitis E are attributable to infection with hepatitis E virus genotypes 1 and 2. DR.T.V.RAO MD 11
  • 12. TRANSMISSION OF INFECTION • The hepatitis E virus is transmitted mainly through the faecal- oral route due to faecal contamination of drinking water. Other transmission routes have been identified, which include DR.T.V.RAO MD 12
  • 14. Prevention and Control Measures for Travelers to HEV-Endemic Regions  Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruit/vegetables not peeled or prepared by traveler.  IG prepared from donors in Western countries does not prevent infection.  Unknown efficacy of IG prepared from donors in endemic areas.  Vaccine? DR.T.V.RAO MD 14
  • 15. TRANSMISSION • Foodborne transmission from ingestion of products derived from infected animals; • Zoonotic transmission from animals to humans; • Transfusion of infected blood products; • Vertical transmission from a pregnant woman to her foetus. DR.T.V.RAO MD 15
  • 16. INCUBATION PERIOD • The incubation period following exposure to the hepatitis E virus ranges from three to eight weeks, with a mean of 40 days. The period of communicability is unknown. DR.T.V.RAO MD 16
  • 17. SYMPTOMS • The hepatitis E virus causes acute sporadic and epidemic viral hepatitis. Symptomatic infection is most common in young adults aged 15–40 years. Although infection is frequent in children, the disease is mostly asymptomatic or causes a very mild illness without jaundice (anicteric) that goes undiagnosed DR.T.V.RAO MD 17
  • 18. CLINICAL PRESENTATION Jaundice • anorexia (loss of appetite); • an enlarged, tender liver (hepatomegaly); • abdominal pain and tenderness; • nausea and vomiting; • fever. DR.T.V.RAO MD 18
  • 19. HEPATITIS E INFECTION AND PREGNANCY • In rare cases, acute hepatitis E can result in fulminant hepatitis (acute liver failure) and death. Overall population mortality rates from hepatitis E range from 0.5% to 4.0%. Fulminant hepatitis occurs more frequently during pregnancy. Pregnant women are at greater risk of obstetrical complications and mortality from hepatitis E, which can induce a mortality rate of 20% among pregnant women in their third trimester. DR.T.V.RAO MD 19
  • 20. CHRONIC HEPATITIS E INFECTION • Cases of chronic hepatitis E infection have been reported in immunosuppressed people. Reactivation of hepatitis E infection has also been reported in immunocompromised people. DR.T.V.RAO MD 20
  • 21. DIAGNOSIS BY DETECTION OF ANTIBODIES • Diagnosis of hepatitis E infection is therefore usually based on the detection of specific antibodies to the virus in the DR.T.V.RAO MD blood. 21
  • 22. NEWER METHODS IN DIAGNOSIS • Reverse transcriptase polymerase chain reaction (RT-PCR) to detect the hepatitis E virus RNA; • Immune electron microscopy to detect the hepatitis E virus. DR.T.V.RAO MD 22
  • 23. TREATMENT • There is no available treatment capable of altering the course of acute hepatitis. Prevention is the most effective approach against the disease. • As hepatitis E is usually self-limiting, hospitalization is generally not required. However, hospitalization is required for people with fulminant hepatitis and should also be considered for infected pregnant women. DR.T.V.RAO MD 23
  • 24. PREVENTION Maintaining quality standards for public water supplies ; Establishing proper disposal systems to eliminate sanitary waste. DR.T.V.RAO MD 24
  • 25. PREVENTION • Maintaining hygienic practices such as hand washing with safe water, particularly before handling food; • Avoiding drinking water and/or ice of unknown purity; • Avoiding eating uncooked shellfish, and uncooked fruits or vegetables that are not peeled or that are prepared by people living in or travelling in highly endemic countries DR.T.V.RAO MD 25
  • 26. VACCINATION - UPDATE • China has produced and licensed the first vaccine to prevent hepatitis E virus infection, although it is not yet available globally. DR.T.V.RAO MD 26
  • 27. • Programme Created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World • Email • doctortvrao@gmail.com DR.T.V.RAO MD 27