HEPATITIS
Dr. Arshi Nafis
Dep - Microbiology
I.T.S Dental College
OBJECTIVES
To study Hepatitis viruses and diseases
caused by viruses.
HEADINGS
MORPHOLOGY of Hepatitis A virus
Classification of Heparnavirus
Mode of transmission:
Pathogenesis of Hepatitis A virus:
Clinical features of Hepatitis A
I. Mild illness without Jundice
II. Acute hepatitis with jaundice
HEADINGS
Laboratory diagnosis of Hepatitis A
1. Liver function test (LFT):
2. Serology
3. Virus culture:
4. Molecular diagnosis
HEADINGS
Morphology of Hepatitis B virus
Mode of transmission of Hepatitis B
Pathogenesis of hepatitis B virus
Primary infection (acute infection)
Chronic infection
Clinical manifestation
Lab diagnosis of HBV
Treatment of Hepatitis B
Prevention and Control
HEPATITIS A
INTRODUCTION
MORPHOLOGY of Hepatitis A virus
Hepatitis A virus (HAV) ia a member of Family Picornaviridae. It
was previously classified as Enterovirus 72. Now it is assigned to
new genus Heparnavirus (Hepatovirus).
HAV is a RNA virus.( 7.48kb )
Genome: the genome is single stranded positive sense RNA (+ss
RNA).. There are 4 viral proteins ie. VP1, VP2, VP3 and VP4. ( VP1
and VP3 are major antibody binding site)
HEPATITIS A
Shape: Small spherical
Capsid: icosahedral
Size: 27nm
Envelope: absent (No envelope)
HEPATITIS A
HEPATITIS A
Replication: In cytoplasm of Host cell
Resistance: HAV is stable to treatment with 20% ether, acid
(pH 1.0 for 2 hours), heat(60C for 1 hours) and temperature of
4C or below.
Susceptible: HAV is destroyed by Autoclaving, boiling in
water for 5 minutes, by dry heat (180 C for 1 hours), by UV
light, formaldehyde (1: 4000 at 37C for 72 hours0 and
chlorine (10-15 ppm for 30 minutes).
HEPATITIS A
Hepatitis A virus causes an acute highly contagious hepatitis,
also known as infectious hepatitis in children and young
adults.
Classification of Heparnavirus; Hepatitis A virus is the only
known species of the genus Hepatovius. There is only one
serotype of HAV and 4 genotypes.
HEPATITIS A
Mode of transmission:
HAV is mainly transmitted through Faeco-oral route by
eating/drinking contaminated food and water.
also transmitted by direct person to person contact
virus is also transmitted by food handlers and children
Rarely transmitted by blood products, blood transfusion or
intravenous drug use.
HAV is excreted in faeces during incubation period of 3-5 weeks.
HEPATITIS A
Pathogenesis of Hepatitis A virus:
Human is the primary reservoir of Hepatitis A virus. The virus
may survive outside the body for months.
HAV infection is caused by ingestion of contaminated foods or
water. The virus first multiplies in the intestinal epithelium
and then enter the blood stream and then migrates to liver
parenchymal cells.
HEPATITIS A
Virus multiplication occurs in hepatocytes and Kupffer’s cells
causing monuclear infiltrate, ballooning of hepatocytes,
degeneration and acidophilic bodies in the hepatocytes.
Liver damage is not due to HAV but rather due to
immunological response by cytotoxic T cells.
Newly synthesized viruses in liver cells sheds into bile ducts
and excreted in faeces.
HEPATITIS A
Clinical features of Hepatitis A:
The incubation period is between 2-10 weeks.
After about 2 weeks of infection, virus is detectable in the
liver blood and faeces.
clinical features includes-
I. Mild illness without Jaundice with little liver cell
damage
Loss of appetite
HEPATITIS A
Nausea
Gastrointestinal upset
Enlarged and painful liver
HEPATITIS A
II. Acute hepatitis with jaundice with severe liver cell
damage
More acute symptoms especially nausea
Loss of appetite
Fever
Jaundice
Headache
Pain in muscle and joint
Skin rashes
HEPATITIS A
Laboratory diagnosis of Hepatitis A:
Specimen: faece, blood
1. Liver function test (LFT):
Increase in both Alanine aminotransferase (ALT) and
Aspartate aminotransferase enzyme by 4-100 times in
Hepatitis patient than normal.
A sharp rise of ALT with short duration (4-20 days) is
suggestive of HAV infection.
Increase serum bilirubin level (5-20 mg/dl)
Increase serum globulin level
HEPATITIS A
2. Serology:
Antibody detection: rapid kit for detection of anti-HAV IgM in
serum
Antigen detection: detection of hemagglutination antigen or
virus particle in faeces
3. Virus culture:
culture of HAV is difficult and takes upto 4 weeks to get result
In cell line culture, virus does not replicate well and produces
variability till cytopathetic effects.
4. Molecular diagnosis:
Electron microscopy
RT-PCR
HEPATITIS B
HEPATITIS B
Hepatitis B virus
Hepatitis B is the most widespread and most important type of
viral hepatitis. Hepatitis B virus (HBV) infects the liver and
to less extent kidney and pancreas.
It belongs to Hepadna viridiae family
It is ds DNA virus. However one of the strand is shorter than
another strand
It has circular DNA
HEPATITIS B
Morphology
HBV is a small, enveloped DNA virus measuring 42
nm in diameter. It has an outer envelope and an inner
core which is 27 nm in diameter enclosing the viral
genome and a DNA polymerase.
Three types of morphological form can be seen;
◦ Small 20-22nm circular or spherical form: this is the most
abundant form and it comprises of viral surface proteins.
◦ 20 x 200 nm filamentous form known as Australia antigen
◦ Double walled 42nm spherical form called Dane particle: this
particle is the complete hepatitis B virus.
HEPATITIS B
Envelope consists of at least three membrane spanning
proteins;
◦ Large Hepatitis B virus surface (LHBS) protein: LHBS
consists of S-domain as well as pre-S-domain (pre-S1 and
pre-S2), both internally and externally. LHBS is important
for infection.
◦ Medium hepatitis B virus surface (MHBS)
protein: MHBS is made up of S-domain and pre-S2 domain
◦ Small hepatitis B virus (SHBS) protein: SHBS consists
of only S-domain. It is the main constituent of virus
envelope and is important for virion assembly
HEPATITIS B
HEPATITIS B
Antigen present in Hepatitis B virus:
There are different types of group specific surface
antigen (HBs Ag.
HEPATITIS B
Surface antigen (HBs Ag) encircles 25-28nm core.
The core antigen is made up of nucleo-capsid which consists
of DNA and capsid (HBc Ag)
HEPATITIS B
Mode of transmission of Hepatitis B:
Hepatitis B is transmitted by the exchange of body fluids-
blood, serum, semen, breast milk and in some circumstances
saliva.
Concentration of HBV in various body fluid:
◦ High: blood, serum, wound exudates
◦ Moderate: semen, vaginal fluids, saliva
◦ Low: urine, feces, sweat, tears, breast milk
HEPATITIS B
Transmission of HBV occurs by following routes:
◦ From infected mother to child
◦ Transfusion of HBV infected blood or blood products
◦ Sexual contact with infected person.
HEPATITIS B
Pathogenesis of hepatitis B virus:
Hepatitis B virus infection is an immune-pathological disease.
HBV after entering the blood infects hepatocytes with the
expression of viral antigen on the surface of infected cells.
Copies of HBV genome integrate into hepatocyte
chromosome and remain latent.
HEPATITIS B
Adaptive immunity is more involved than the innate
immunity in causing tissue destruction.
Primary infection (acute infection):
The incubation period of HBV is usually 4-10 weeks
HBs Ag begins to appear in the serum during the incubation
period and continues to increase..
HEPATITIS B
Anti-HBc IgM antibody begins to rise with the onset of
symptoms and this is the marker of acute infection.
As HBs Ag become detectable, there is also marked increase
in viral titer which can peak upto 109 to 1010 virions/ml.
HBe Ag also become detectable. By this time 70-80% of liver
cells are infected.
HEPATITIS B
Once the response begins, viral titers from liver and blood
begin to decline.
With clearance of virus, HBs Ag and HBe Ag level disappear.
Subsequently level of anti-HBs Ag begins to rise.
HEPATITIS B
Chronic infection:
A chronic carrier of HBV is an important event in
the pathogenesis.
Persistent infection of hepatocytes result in
presence of HBV and HBs Ag in blood for at least 6
months. Whether an infected host cell will become
a chronic carrier state or will be free of infection
depends on the cytotoxic T-cell response.
HEPATITIS B
Clinical manifestation:
Clinical disease in susceptible host can be symptomatic or
asymptomatic. Asymptomatic cases are more common in
children.
Infection in adults whether it is symptomatic or asymptomatic,
is self-limited which may be due to virus clearance or immune
response of individuals towards the virus.
HEPATITIS B
Acute hepatitis B:
It is characterized by gradual onset of anorexia,
malaise and fatigue.
During Acute (icteric) phase, the liver become
tender with the development of jaundice, nausea,
vomiting and passing of dark colored urine
HEPATITIS B
Chronic hepatitis B:
5% of the adults may develop persistent infection.
Persistent infection can also be symptomatic or
asymptomatic.
In people with sub-clinical persistent infection, normal level
of serum amino-transferase and normal or nearly normal
findings on liver biopsy indicates asymptomatic chronic
persistent infection.
HEPATITIS B
However abnormal liver function test and histological
findings on biopsies indicate symptomatic chronic
persistent infection.
Depending upon the extent of viremia and host response,
chronic infection can lead to liver cirrhosis and hepato-
cellular carcinoma (HCC).
HEPATITIS B
Lab diagnosis of HBV:
The initial diagnosis of Hepatitis B is made on the basis of
clinical features and laboratory findings on serum bilirubin
and enzymes transaminase, ALT and AST
Specimen: Blood, serum, body secretions
Microscopy: Immunofluorescence staining:
◦ Immunofluorescence staining of infected hepatocytes show HBV core
antigen in the nucleus and infectious Dane particle in cytoplasm.
Molecular diagnosis:
◦ Detection of viral DNA by molecular methods such as PCR in tissue
sample and serum reflects the degree of virus replication in liver.
HEPATITIS B
Serology: Appear Standard serological test of HBV is
detection of HBs Ag.
HBs Ag is the first marker to appear in blood after
infection. It can be detected even before elevation of
transaminase enzymes and onset of clinical symptoms.
HBs Ag remains in blood circulation throughout the acute
phase of disease.
When HBs Ag is no longer detectable, its antibody (anti-
HBs) appears and is detectable for longer period.
HEPATITIS B
Detection of IgM anti HBs indicates recent infection while
detection of IgG anti-HBs indicates past infection.
Presence of anti-HBs without other serological virus
marker indicates immunity following vaccination.
HBc Ag is not detectable in blood because it is enclosed
within HBs Ag. But anti-HBc antibody appears in serum
1-2 weeks after appearance of HBs Ag.
HBe Ag appears in blood concurrently with HBs Ag or
soon afterwards. The disappearance of HBe Ag coincides
with the fall of transaminase levels in blood which is
followed by anti-HBe Antibody.
HEPATITIS B
Antigen detection
Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen
(HBeAg) are the acute Hepatitis B infection markers.
HBsAg: It is the surface antigen of hepatitis B and is also
called Australia antigen or hepatitis-associated antigen.
HBsAg generally appears before the onset of symptoms and
peaks during overt disease. In patients who successfully clear
the HBV infection and do not progress to the chronic carrier
stage, HBsAg typically is undetectable 4 to 6 months after
infection. The presence of HBsAg even after six months
indicates chronic infection.
HEPATITIS B
HBeAg: HBeAg is a soluble protein in the core of the
hepatitis B virus (HBV). It is generally considered to be a
marker of HBV replication and infectivity. HBeAg arises
during incubation and is present during the prodrome, early
acute disease, and certain chronic carriers. Its presence in
chronic carriers indicates a high likelihood of
transmissibility; conversely, the absence of HBeAg
indicates a low likelihood of transmission.
HEPATITIS B
Treatment of Hepatitis B
No specific antiviral therapy is available to treat acute
hepatitis B infection. Treatment of symptoms is the only
measure in treating acute disease. The antiviral therapy is
recommended for chronic cases. The treatment with
interferons and nucleoside analogs is the standard method
used. These do not cure HBV but only prevent morbidity and
complications related to HBV infections.
HEPATITIS B
Prevention and Control
The preferable method to prevent and control HBV
infections is both vaccines and immunoglobulins .
Immunoglobulin: The passive immunization just before
or after exposure to the virus with HBIg. It is obtained
from the patients who have recovered from the infection
and contains a high titer of HBsAb. It is recommended to
those in recent contact with infected people, who are to be
in household contact with the infected people, infants
born with HBsAg positive mothers, and those in sexual
contact with acutely infected patients..
HEPATITIS B
Vaccines: Plasma-derived and recombinant
DNA HBV vaccines are the two types of
vaccines available with HBsAg that generates
anti-HBs. Recommended vaccine schedule for
adults is at 0,1 and 6 months, and infants are
at birth, at 1-2 months, and 6-18 months.
CONCLUSION
MORPHOLOGY of Hepatitis A virus
Classification of Heparnavirus
Mode of transmission:
Pathogenesis of Hepatitis A virus:
Clinical features of Hepatitis A
Laboratory diagnosis of Hepatitis A
CONCLUSION
Morphology of Hepatitis B virus
Mode of transmission of Hepatitis B
Pathogenesis of hepatitis B virus
Clinical manifestation
Lab diagnosis of HBV
Treatment of Hepatitis B
Prevention and Control
Suggested books
Text book of microbiology C P Baveja.
Ananthnarayan, Paniker, Textbook of Microbiology
PYQ
Clinical features and diagnosisof Hepatitis B.
Reference
Text book of microbiology C P Baveja.
Ananthnarayan, Paniker, Textbook of Microbiology
THANK
Dr. Arshi Nafis
Asst. Professor
Microbiology
I.T.S Dental College
