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VIRUS HEPATITIS

Enny Suswati, dr. MKes.


Lab. Mikrobiologi Fakultas Kedokteran
UNEJ
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ICTERUS
CAUSED BY :

Pre hepatic disorder


Malaria, erytrocyt lysis

Hepatic disorder
Viral infection ( cmv, hav, hbv..)
Bacterial infection
Toxic agemt or drug

Post hepatic disorder


Bile obstruction, carcinoma on head of
pancreas
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HEPATITIS
Inflammation on the liver
Ussually caused by:
Viral infection
Toxic agent
Drug abuse

Symptoms : icterus/ joundice, right


abdominal pain, liver enlargement, mild
fever
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HEPATITIS A VIRUS (HAV)


A Picorna virus family
Genus heparna virus
Naked icosahedral form ( non
enveloped)
Genom: single stranded (ss) RNA

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With 7478 nucleotides which encode


for 4 protein : VP 1, VP2,VP3,VP4
Only 1 serotype
Can be propagated in marmosets cell
culture and in vivo in chimpanzees and
marmosets

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EPIDEMIOLOGY

Endemic in all parts of the world


High incidence in developing countries
High proportion of subclinical infections
Transmission is associated with faecally
contaminated food and water

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Common in bad sanitation, and over


crowded population
Traveler can be infected HAV in
hyperendemic area
Mainly fecal oral transmission
Rarely by parenteral mode

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In children, ussually the infection is


subclinical or mild, but in adults ussually
more serious
Incubation periode:
3-5 weeks (15-40 days), with mean 28 days

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PATHOGENESIS
Patholical changes : parenchymal cell
imflamation and necrosis, also
periportal inflamtion
Serum billirubin may be elevated

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Elevated liver enzymes


ALT (alanin amino transferase)
AST (aspartat amino transferase)
SGOT (serum glutamic oksaloasetic
transaminase)
SGPT (serum glutamic piruvic transaminase)

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CLINICAL FEATURES
Commonly after 4 weeks incubation
periode
Non spesific symptoms : fever, chill, muscle
aches / pain, headache, fatigue, malaise.
Followed by spesific symptoms : anorexia,
nousea, vomitt, and right abdominal pain.

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Dark urine and pale stools


Icterus/joundice in few days and persist for
1-2 weeks
Covalescense and complete recovery
ussually within few months.
No cronical features, mortality rate is very
low
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DIAGNOSIS
1. Detection of the virus or antigen
Can be detected in feces, until 2 weeks after
joundice dissapear, also in serum, saliva, urine

2. Antibody detection
Choiced metode for diagnosis of acute
hepatitis A
IgM anti HAV will be detected on recent
infection
IgG anti HAV is used to determining immune
status
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PREVENTION

Symple hygienic
Sanitary disposal of feces
Vaccine from killed or live attenuated virus
Immunoglobulin anti HAV
For closed personal contact with patients
Prophylaxis for traveler to high endemic area
Valid until 6 months

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HEPATITIS B VIRUS

Genome is a double stranded (ds) DNA


Family hepadnaviridae
Diameter about 42 nm (10 -9 m)
Have an outer shell or envelope

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EPIDEMIOLOGY
Hepatitis B is common / high incidence in
asia, africa, south america. Low in europe
and north america
Estimated more than 5 % the global
population were infected by HBV

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Replication

Virus enter the body of a new host


Passed the immune system barrier
Attached to liver cell membrane
Virus core particle entered the liver cell and
release its contents of HBV DNA and
enzyme DNA polymerase into liver cell
nucleus

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HBV DNA, via mRNA force the liver cell


to produce:

Surface protein ( HBs)


Core Protein (HBc)
HBe protein
DNA polymerase

DNA polymerase causes the liver cell make


copies of HBV DNA
New viruses are release from the liver cell
membrane into blood stream
Can infect another liver cell effectively
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HBV ANTIGENS

1. HBV DNA
2. HBV DNA Polymerase
3. Hepatitis B surface (HBsAg)
4. Hepatitis B core (HBc Ag)
5. Hepatitis B envelope ( HBe Ag)

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1. HBV DNA
indicate how fast the virus is replicating.
However, the test for HBV DNA is
expensive and difficult, there for not
frequently used.
2. HBV DNA Polymerase
This enzym also not frequently used

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3. HBs Ag
Frequently used
After infection and 1-6 weeks before symptoms
occur this antigen could be detected
HBs Ag possitive is indicate current infection

4. HBc Ag
Not detectable on blood stream
Can detected by liver biopsy
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5. HBe Ag
HBe Ag is a peptide and detectable in
bloodstream when the HBV reproducing
actively
In Acute infection HBe Ag generally only
transiently present
The presence of HBe Ag in cronic infection
indicate that HBV still actively reproducing

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HUMAN BODY RESPONS


90 % will recover completely, its mean no HBs
Ag found and HBs Ab is present. HBs Ab
ussually persist for live after recovery
Anti bodies (Ab) to HBs Ag : (HBs Ab)
Anti bodies (Ab) to HBc Ag : (HBc Ab)
Anti bodies (Ab) to HBe Ag : (HBe Ab)
ALT , AST and SGOT , SGPT increase
Interferon produce to fighting HBV
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TRANSMISSION
HBV transmitted by exchange of the body
fluids e.g.: blood, serum, semen, breastmilk,
saliva, vaginal fluids.
High risk people:
Unprotected sexual intercourse, hetero or homo
sexual
Drugs user who share needles
Babie born to mothers with the HBV
Health Care Worker
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Clinical Features

The incubation : 6-25 weeks


Can be asymptomatic
Joundices
The symptoms are like in HAV infection :
fatigue, lost of appetite, nousea, vomitt,
right abdominal pain, icterus

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90 % infected people will be recover


completely and immune to this virus
10% infected people will develope into
chronic infection
Chronic infection if HBs Ag persist for
more 6 months

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Chronic infection:
Persistens chronic hepatitis
Progressive chronic hepatitis

20%-30% of Chronic infection will


progress to cirrhosis
Can lead to hepatocellular carcinoma
(hepatoma)
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DIAGNOSIS

1.
2.
3.
4.

Serological tests are used for diagnosis of acute


and chronic hepatitis B infection:
HBs Ag
Used as general marker of HBV infection
HBs Ab
used to document recovery and immunity to
HBV infection
IgM anti HBc
marker of acute HBV infection
IgG anti HBc
marker of past or chronic HBV infection

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5. HBe Ag
indicate active replication of the virus and
infectiveness
6. Anti HBe
virus no longer replicating.
7. HBV DNA
indicate active replication of virus. Rarely
used
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PREVENTION
Before infection
Give HBIG ( Hepatitis Immuno Globulin)
Vaccination
3 times sub cutaneous injection, in 6 months
(0,1,6)
Give immunity in 90 - 95 % of people treated
Booster dose every 5-10 years to ensure
immunity
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Dont share razors, toothbrush, needle, ect.


Use latex condom if your sex partner were
infected or suspected
Screening for blood donor

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After exposed with HBV:


E.g. needle injury, new infants / babies born to
HBs Ag possitive mother
Give HBIG (Hepatitis Immuno Globulin)
Ideally within 24 hours of exposure no later
than 7 days

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HEPATITIS C VIRUS

Formerly called Non A non B virus


Family flaviviridae
Genom single sranded (ss) RNA
Icosahedral with envelope

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Epidemilogy
Majority of infected people are from blood
transfusion
Transmission :
Trans venous drug admisssion, transfusion,
sexual intercourse, from mother to infant

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Clinical features
The symptoms are simmilar with Heaptitis
A and B infection
85% people who infected by HCV are
become chronic
Once chronically infection, the viru is
almost never cleared
Some go on to develop cirrhosis and Hepato
Cellular Carcinoma
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Diagnosis
Serologic test
Presence of anti-HCV antibodies
Liver biopsy to assess the degree of liver
inflammation and fibrosis and presence of
cirrhosis
Patients with advance cirrhosis should be
evaluated for possible liver transplantation
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HEPATITIS D VIRUS (HDV)


HDV cannot produce invective virions
without the coinfecting helper virus
This helper virus is HBV that supplies the
HBs Ag surface protein
In budding out of the cell, HDV acquires a
membranes containing HBs Ag

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HDV is a small circular genome, The RNA


encodes a protein called delta antigen
The RNA is single stranded. With envelope

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Transmission
Parenteral exposure
Injection, transfusion, ect.

Permucosal exposures
Sexual contact

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Clinical features
HDV can be acquired either as:
A co-infection (occur simultaneously) with
HBV or
A super infection in persons with existing
chronic HBV infection

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HDV HBV co infection:


More severe acute, higher risk to develop acute
liver failure than HBV alone

HDV HBV super infection:


Chronic HBV carrier who acquired HDV
superinfection ussually develop chronic HDV
infection
Progressive to cirrhosis
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HEPATITIS E VIRUS

Causes enteric Non A non B hepatitis


Simmilar to Calicivirus
Icosahedral
Ss RNA virus
Hane not envelope

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Epidemiology
Most outbreaks Associated with faecally
contaminated drinking water
Large epidemics have occurred in indian,
USSr, China, Africa and Mexico
Minimal person to person transmission

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Clinical features
Incubation period:
Average 40 days, range 15-60 days

Case fatality rate:


Overall 1 - 3%
In pregnant women 15-25 %

Illness severity : increased with age


Crhonic sequele : none identified
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Prevention
Avoid drinking water ( and baverage with
ice) of unknown purity, uncooked shellfish
and uncooked fruits/vegetable not peeled.
Vaccine : ?

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