Viral hepatitis is a systemic disease primarily involving the liver.
Hepatotropic viruses : liver is the target organ and the main site of virus replication
Hepatitis A virus (HAV)
hepatitis B virus (HBV)
Hepatitis C virus (HCV)
Hepatitis D virus (HDV, delta virus)
Hepatitis E virus (HEV).
Enterically:
virus is spread from person-to-person by putting something in the mouth that has been contaminated with the stool of a person with hepatitis E. This type of transmission is called "fecal-oral." For this reason, the virus is more easily spread in areas where there are poor sanitary conditions
2. Viral hepatitis is a systemic disease primarily
involving the liver.
Hepatotropic viruses : liver is the target organ and
the main site of virus replication
• Hepatitis A virus (HAV)
• hepatitis B virus (HBV)
• Hepatitis C virus (HCV)
• Hepatitis D virus (HDV, delta virus)
• Hepatitis E virus (HEV).
3. Other viruses also infect other sites of the body, and
therefore are not exclusively hepatitis viruses.
• Yellow fever virus.
• Epstein-barr virus.
• Cytomegalovirus.
4. The clinical manifestations of hepatitis are the same,
regardless of which virus is the cause.
is characterized by: Fever+ gastrointestinal symptoms
( anorexia, nausea, vomiting) +
Jaundice No jaundice
↓ ↓
icteric hepatitis anicteric hepatitis
(is more common).
5. Hepatotropic viruses
Transmitted enterically Transmitted parenterally
-Intravenous route
virus is transmitted by contaminated food Intramuscular route
and water: Subcutaneous route
Intradermal route
HAV and HEV
HCV, HBV and HDV
6. Enterically transmitted hepatitis
viruses
Hepatitis A virus
Classification
• Family: Picornaviridae
• Genus: hepatovirus
• Only one serotype is known
7. Properties
• Icosahedral nucleocapsid.
• Nonenveloped.
• Genome: a single stranded RNA.
• The virus is stable to treatment with ether, acid and heat
(60°C for 1 hour).
• It can be destroyed by autoclaving) to sterilize)boiling for
5 min, or by chlorine.
9. Transmission and epidemiology
HAV is transmitted by the fecal-oral route.
• Under crowded conditions and poor sanitation,
infection occurs at an early age, most children
become immune by age 10.
• With higher levels of poor sanitation, infection
occurs in older persons.
10. Clinical findings
IP: 3-4 weeks
Clinical illness:
• Asymptomatic infection is common in infants and
children.
• Disease is more severe in adults. (is symptomatic
infection)
Outcome of infection:
Almost all cases (99%) recover completely in 2-4
weeks with life long immunity( no repeat infection)
There is no chronicity.
11. Pathogenesis
• Following ingestion, HAV enters the bloodstream
through the epithelium of the oropharynx or
intestine.
• The blood carries the virus to its target, the liver,
where it multiplies within hepatocytes and
Kupffer cells (liver macrophages).
• Virions are secreted into the bile and released in
stool.
• HAV is excreted in large quantities approximately
15 days prior to appearance of symptoms or anti-
HAV IgM antibodies in the blood
12. Hepatitis A Infection
Typical Serological Course
Symptoms Total anti-
HAV
Titre ALT
Fecal
HAV
IgM anti-HAV
0 1 2 3 4 5 6 1 2
2 4
Months after exposure
13. Laboratory diagnosis
Detection of HAV antibodies:
• Anti-HAV IgM → acute hepatitis A
• Anti-HAV IgG → past infection or vaccination.
• ELISA is the method of choice for detecting these
antibodies.
Detection of HAV antigen:
In stools by ELISA.
Detection of HAV RNA:
In stools by PCR and nucleic acid hybridization.
14. Prevention and control
Prevention of fecal contamination of food and
water.
Good hygiene-hand washing.
Chlorination of water
15. Active immunization
A formalin inactivated HAV vaccine IS AVAILABLE
• Safe and effective
• Recommended for use in persons over 1 year of age.
• Two doses should be given: an initial dose , booster dose
6-12 months later.
Passive immunization
Immune (gamma) globulin confers passive protection
when given 1-2 weeks after exposure to hepatitis A.
Immune globulin does not prevent the infection but makes
it mild or subclinical.
17. Transmission
HEV is transmitted enterically.
Clinical findings
IP: ~ 40 days
The disease resembles hepatitis A.
WITH EXCEPTION of A high mortality rate in pregnant
women (fulminant hepatitis).
Chronic liver disease does not occur.
18. Diagnosis
Detection of:
Anti-HEV antibodies.
HEV-RNA in serum.
Prevention and control
General measures as with hepatitis A.
There is no vaccine.
19. Parenterally-transmitted hepatitis
viruses
Hepatitis B virus
Properties
Member of the hepadnavirus family.
42 nm enveloped virion.
Icosahedral nucleocapsid containing a partially
double-stranded circular DNA genome.
20. Electron microscopy of a patient s serum
reveals three different types of particles
These two forms are made
up exclusively of surface
antigen *
The virus is one of the smallest enveloped animal viruses, but
pleomorphic forms exist
22. Pathogenesis
• Although replication takes place in the
liver, the virus spreads to the blood where
viral proteins and antibodies against them
are found in infected people.
23. Epidemiology and Transmission
HBV is worldwide in distribution. Egypt lies within
the zone of moderate prevalence of chronic carriers
(2-7% of the population is HBsAg positive).
High titers of the virus: blood and serum.
Moderate levels: semen, saliva and vaginal secretion.
24. Geographic Distribution of Chronic HBV
Infection
HBsAg Prevalence
≥8% - High
2-7% - Intermediate
<2% - Low
25. Three main modes of transmission.
1-Percutaneous and permucosal exposure
to blood.
2- Sexual transmission.
3- Perinatal transmission.
26. 1-Percutaneous and permucosal exposure to blood.
Transfusion of blood and blood products.
Sharing of contaminated needles and syringes.
The use of improperly sterilized instruments (even
in tattooing and ear piercing).
Sharing of razors and tooth brushes.
2- Sexual transmission.
3- Perinatal transmission from mother to newborn.
During birth or breast feeding.
In-utero transmission is rare.
27. Clinical features
The mean incubation period is 10-12 weeks.
Many HBV infections are asymptomatic. Symptoms are
similar to that of hepatitis A, but tend to be more severe.
Outcome of infection
Adults Infants and young children
↓ ↓
90-95% recover completely. 80-95% chronic carriers.
28. Spectrum of chronic hepatitis B diseases
Most chronic carriers are asymptomatic.
Some develop chronic hepatitis → cirrhosis, liver failure
and death.
Chronic carriers are at high risk of developing
hepatocellular carcinoma, especially those infected as
infants.
HBV vaccine is the first vaccine to prevent a human
cancer.
30. Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg anti-HBe
Total anti-HBc
Titer
HBsAg IgM anti-HBc anti-HBs
0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure
31. Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Acute Chronic
(6 months) (Years)
HBeAg anti-HBe
HBsAg
Total anti-
HBc
Titer
IgM anti-HBc
0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure
32. Laboratory diagnosis
HBV antigen and antibodies are usually
detected in serum by ELISA.
HBV DNA is detected by PCR.
33. Interpretation of results
Serologic tests can identify four stages of HBV infection.
Test Acute Window Complete Chronic
disease phase recovery carrier
state
HBsAg Positive Negative Negative Positive
Anti-HBs Negative Negative Positive Negative
Anti-HBc Positive Positive Positive Positive
34. Persons immunized with HBV vaccine have anti-HBs but
not anti-HBc because the vaccine is purified HBsAg.
The presence of HBeAg → high probability of
transmissibility.
The presence of anti-HBe → lower probability, but
transmission can still occur.
The detection of viral DNA in the serum is strong
evidence that infectious virions are present.
35. Prevention and control
I-Hepatitis B vaccination is the most effective measure
to prevent HBV and its consequences.
1 .Plasma derived vaccine:
Purified HBsAg from healthy HBsAg positive carriers.
2. Recombinant DNA derived vaccine:
HBsAg produced in yeast cells by recombinant DNA
techniques.
36. The vaccine is recommended for:
1. All infants as part of their regular immunization
schedule.
2. Heath care personnel frequently exposed to blood or
blood products.
3. Patients receiving multiple transfusions or dialysis.
The vaccine is given in a three-dose regimen
0, 1, 6 months.
37. II-Hepatitis B immune globulin (HBIG) is used to
provide immediate, passive protection if it is given
soon after exposure.
Both the vaccine and HBIG should be administered
simultaneously (at different sites) to:
Persons exposed to HBV percutaneously or by
contamination of mucosal surfaces.
Infants born to HBV-positive mothers.
Both immediate and long term protection are
provided.
38. III-General measures
1. All blood for transfusion should be screened for HBV.
2. Proper sterilization of endoscopes and surgical instruments.
3. Only disposable needles and syringes should be used.
4. Standard precautions to prevent percutaneous injuries or
contact of non intact skin or mucous membrane with blood or
body fluids:
Gloves should be worn when handling potentially
infectious material.
Proper handling and disposal of sharps.
Decontamination of spillage accidents with chlorine.
Notas del editor
Enterically: virus is spread from person-to-person by putting something in the mouth that has been contaminated with the stool of a person with hepatitis E. This type of transmission is called "fecal-oral." For this reason, the virus is more easily spread in areas where there are poor sanitary conditions.
An autoclave is a device used to sterilize equipment and supplies by subjecting them to high pressure saturated steam at 121 °C for around 15–20 minutes depending on the size of the load and the contents
9 Following exposure to HAV , Virus particles are found in the stools from about 2 -3 weeks before the onset of jaundice During the acute stage of the infection, the liver enzyme alanine transferase (ALT) is present in the blood at levels much higher than is normal. The enzyme comes from the liver cells that have been damaged by the virus Anti HAV IgM appears during the acute phase and declines to undetectable levels within 3 – 6 months Anti HAV IgG appears later and gives life long protection
The outer shell or enveloppe is host cell derived and contains a protein called hepatitis B surface antigen ( HBsAg) The inner core ( nucleocapsid) is composed of the core protein ( HBcAg) and encloses the viral genome associated with viral DNA polymerase Another core antigen known as HBeAg is secreted in a soluble form