hepatitis a, e, b
DESCRIPTION
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 conditionsTRANSCRIPT
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).
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).
Other viruses also infect other sites of the body, and
therefore are not exclusively hepatitis viruses.
• Yellow fever virus.
• Epstein-barr virus.
• Cytomegalovirus.
Other viruses also infect other sites of the body, and
therefore are not exclusively hepatitis viruses.
• Yellow fever virus.
• Epstein-barr virus.
• Cytomegalovirus.
The clinical manifestations of hepatitis are the same,
regardless of which virus is the cause.
is characterized by: Fever+ gastrointestinal symptoms
( anorexia, nausea, vomiting) +
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
icteric hepatitis
Jaundice
icteric hepatitis
No jaundice
anicteric hepatitis
(is more common).
No jaundice
anicteric hepatitis
(is more common).
Hepatotropic virusesHepatotropic viruses
HCV, HBV and HDV HCV, HBV and HDV
Transmitted entericallyTransmitted enterically Transmitted parenterallyTransmitted parenterally
HAV and HEVHAV and HEV
virus is transmitted by contaminated food and water:
-Intravenous route Intramuscular route Subcutaneous route Intradermal route
Enterically transmitted hepatitis
viruses
Hepatitis A virus
Classification
•Family: Picornaviridae
•Genus: hepatovirus
•Only one serotype is known
Enterically transmitted hepatitis
viruses
Hepatitis A virus
Classification
•Family: Picornaviridae
•Genus: hepatovirus
•Only one serotype is known
Properties
• Icosahedral nucleocapsid.
• Nonenveloped.
• Genome: a single stranded RNA.
• The virus is stable to treatment with ether, acid and heat
(60C for 1 hour).
• It can be destroyed by autoclaving boiling for
5 min, or by chlorine.
Properties
• Icosahedral nucleocapsid.
• Nonenveloped.
• Genome: a single stranded RNA.
• The virus is stable to treatment with ether, acid and heat
(60C for 1 hour).
• It can be destroyed by autoclaving boiling for
5 min, or by chlorine.
(to sterilize (
Hepatitis A VirusHepatitis A Virus
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.
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.
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.
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.
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
FecalHAV
Symptoms
0 1 2 3 4 5 6 12
24
Hepatitis A Infection
Total anti-HAV
Titre ALT
IgM anti-HAV
Months after exposure
Typical Serological Course
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.
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.
Prevention and control
Prevention of fecal contamination of food and
water.
Good hygiene-hand washing.
Chlorination of water
Prevention and control
Prevention of fecal contamination of food and
water.
Good hygiene-hand washing.
Chlorination of water
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.
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.
Hepatitis E virus
Properties The virus is a small.
Non enveloped.
Single stranded RNA virus.
Hepatitis E virus
Properties The virus is a small.
Non enveloped.
Single stranded RNA virus.
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.
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.
Diagnosis
Detection of:
Anti-HEV antibodies.
HEV-RNA in serum.
Prevention and control
General measures as with hepatitis A.
There is no vaccine.
Diagnosis
Detection of:
Anti-HEV antibodies.
HEV-RNA in serum.
Prevention and control
General measures as with hepatitis A.
There is no vaccine.
Parenterally-transmitted hepatitis
virusesHepatitis B virus
Properties Member of the hepadnavirus family. 42 nm enveloped virion. Icosahedral nucleocapsid containing a partially
double-stranded circular DNA genome.
Parenterally-transmitted hepatitis
virusesHepatitis B virus
Properties Member of the hepadnavirus family. 42 nm enveloped virion. Icosahedral nucleocapsid containing a partially
double-stranded circular DNA genome.
Electron microscopy of a patient s serum reveals three different types of particles
The virus is one of the smallest enveloped animal viruses, but pleomorphic forms exist
These two forms are made up exclusively of surface antigen *
Hepatitis B VirusHepatitis B Virus
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.
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.
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.
Geographic Distribution of Chronic HBV Infection
Geographic Distribution of Chronic HBV Infection
HBsAg Prevalence
8% - High
2-7% - Intermediate
<2% - Low
Three main modes of transmission.
1-Percutaneous and permucosal exposure
to blood.
2- Sexual transmission.
3- Perinatal transmission.
Three main modes of transmission.
1-Percutaneous and permucosal exposure
to blood.
2- Sexual transmission.
3- Perinatal transmission.
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.
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.
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
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
90-95% recover completely.
Adults
90-95% recover completely.
Infants and young children
80-95% chronic carriers.
Infants and young children
80-95% chronic carriers.
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.
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.
Virologic and serologic events
following exposure to HBV
Virologic and serologic events
following exposure to HBV
Acute Hepatitis B Virus Infection with RecoveryAcute Hepatitis B Virus Infection with Recovery
Typical Serologic CourseTypical Serologic Course
Weeks after ExposureWeeks after Exposure
TiterTiter
Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc anti-HBsHBsAg
0 4 8 12 16 20 24 28 32 36 52 100
Progression to Chronic Hepatitis B Virus InfectionProgression to Chronic Hepatitis B Virus InfectionTypical Serologic CourseTypical Serologic Course
Weeks after ExposureWeeks after Exposure
TiterTiter
IgM anti-HBc
Total anti-HBc
HBsAg
Acute(6 months(
HBeAg
Chronic(Years(
anti-HBe
0 4 8 12 16 20 24 28 32 36 52 Years
Laboratory diagnosis
HBV antigen and antibodies are usually
detected in serum by ELISA.
HBV DNA is detected by PCR.
Laboratory diagnosis
HBV antigen and antibodies are usually
detected in serum by ELISA.
HBV DNA is detected by PCR.
Interpretation of results Serologic tests can identify four stages of HBV infection.
Interpretation of results Serologic tests can identify four stages of HBV infection.
TestAcute disease
Window phase
Complete recovery
Chronic carrier state
HBsAgPositiveNegativeNegativePositive
Anti-HBsNegativeNegativePositiveNegative
Anti-HBcPositivePositivePositivePositive
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.