HEPATITIS VIRUS

Efrida Warganegara

HEPATITIS
VIRUS

1.
2.
3.
4.
5.
6.
7.
8.

Hepatitis Virus
Hepatitis Virus
Hepatitis Virus
Hepatitis Virus
Hepatitis Virus
Hepatitis Virus
Hepatitis Virus
T T Virus

A
B
C
D
E
F
G

Introduction

Hepatitis means inflammation and damage to the

liver, and can be caused by infection by various
organism, inclufing bacteria (leptospira sp.), viruses
(hepatitis A, B, dan C), or parasites (Schistosoma
mansoni)
Viruses are the most common infectious causess of
hepatitis. at least 5 different viruses are referred to as
Hepatitis virus, and they generally cannot distinguish
clinically
The disease may manifest as acute hepatitis (hepatitis
A, B, or E) or chronic hepatitis (hepatitis B or C).
In hepatitis B or C infection, progressive liver damage,
liver failure, or even liver cancer may result.

KEY CONCEPTS
Display

marked tropism for liver

cells
Use either :

hit & run infectious strategy

(Hepatitis virus A & E)

results in acute infection that is
cleared by the immune system
hide & infiltrate strategy

(Hepatitis virus B, C, Delta, G)

lead to chronic infection

KEY CONCEPTS
Cause

similar symptoms during

the acute stage of infection that
result of liver damage
Can be identified by testing for
presence of specific viral proteins,
specific antibodies against these
proteins or viral nucleic acid
Can be treated with agents such
as interferon, however treatment
for chronic carriers of hepatitis B,
C, D and G generally ineffective
Vaccine exist : A & B

Viral Hepatitis - Historical

Perspectives

Infectious
/ Catarrhal

Viral hepatitis

Serum

Enterically
E
E transmitted

NANB

B
B D
D

C Parenterally
transmitted
F, G, TTV
? other

Virus
Family
Genus

Hepatitis A Hepatitis B

Hepatitis C

Hepatitis D Hepatitis E

Picornaviridae Hepadnaviridae Flaviviridae

None
Hepatovirus Orthohepadna eHep-c-virus
Deltavirus
virus
Virion
Icosahedral
Spherical,
Spherical,
Spherical,
27 nm
42 nm
30-60 nm
35 nm
Envelope
No
Yes (HBsAg)
Yes
Yes(HBsAg)
Genome
ssRNA
dsDNA
ssRNA
ssRNA
Size
7,8 kb
3,2 kb
9,4 kb
1,7 kb
Stability
Heat & acid Acid-sensitive Eter-sensitive Acid-sensitive
stable
Acid-sensitive
Transmission Faecal-oral
Parenteral
Parenteral
Parenteral
Prevalence
High
High
Moderate
Low,
regional
Fulminant
Rare
Rare
Rare
Rare
disease
Chronic
Never
Often
Often
Often
disease
Oncogenic
No
Yes
Yes
?

Caliciviridae
(Unnamed)
Icosahedral,
27-34 nm
No
ssRNA
7,5 kb
Heat-stable
Faecal-oral
Regional
In
pregnancy
Never
No

General symptoms of hepatitis virus

infection
Acute inflammation
Prodromal signs :
Fever
Gastrointestinal symptoms
Jaundice/ icteric
Hepatitis virus type A
Hepatitisenteric
virus type E
Hepatitis
acutevirus type B
parenteral
Hepatitis
virus type C
chronic
Hepatitis virus type D

cirrhosis
Hepatitis
virus type G
hepatocellular-Ca

chronic

Introduction
The

disease picture is a febrille illness of

prolong duration marked by jaundice, fatique
and malaise, abdominal pain, loss of appetite,
anorexia and nausea,

Chronic

hepatitis can be associated with a

rash, due to immune complex-associated
vasculitis, and with arthritis.

Common

risk factor include eating

contaminated seafood (hepatitis A), multiple
sexual partners unprotected intercouse
(hepatitis B), intravenous drug use (hepatitis
C), or blood transfusion.

HEPATITIS
ACUTE
ASYMPTOMATIC
FULMINANT
Severity of the disease depend on :
* virus type
* individual
More than cases asymptomatically
Chronic hepatitis symptoms exist
increasing enzyme levels
> 6 months
Chronic persistent chronic active hepatitis
(mild)
Enzymes levelcirrhosis
Normal hepatic failure
hepatocellular-Ca

Introduction

Clinical diagnosis on the basis of jaundice must

be confirmed by 1) liver function test : level of
serum aminotransferase, bilirubin and alkaline
phosphatase; and 2) hepatitis serologis : virusspecific antigen and antibody markers in serum.

Dramatic elevation of serum aminotransferase

(alanine dan aspartat aminotransferas) are
characteristic of acute viral hepatitis

Specific laboratory test for hepatitis A and B

viruses have been available for some years,
originally referred to as nonA-nonB viruses are
now becoming available.

Introduction

More than half the liver must be damaged or

destroyed before liver function fails.

Regeneration of liver cells is rapid but fibrous repair,

especially when infection persist can lead to cirrhosis

Managemen is mostly symptomatic,

Except in the cases of hepatitis A and B, there are no

licensed vaccine, and

although specific treatments are available chronic

stage of hepatitis B and C (e.g. interferron), there are
no specific treatmens for this disease.

Chronic hepatitis C is the most common cause of

liver failure and subsequent liver transplantation

Control
Screening blood
donor for
hepatitis
viruses B, C
Immunization (active
or
passive)
Treatment :
Interferon

HEPATITIS A VIRUS (HAV)

Discovered by Cockayne tahun 1912
Cause infectious hepatitis, acute
A distinct member of the Picornaviridae family
(previously
Enterovirus 72), a new genus
:
Hepatovirus
Only 1 serotype
27 32 nm, spherical particle, cubic symetry
Containing a linear ss-RNA genome with a size
7.5 kb,
surround by capsid consist of 4 polypeptide
:
VP1 VP4, nonenveloped
The most likely mode of transmission : fecal-oral

Virus stability :
Virus is destroyed by :
Autoclaving 121oC, 20 minutes
Boiling in water for 5 minutes
Oven (dry heat 1800C), for 1 hour
UV irradiation, 1 minute at 1,1 watts
Treatment with formalin 1 : 4000 for
3 days at
370C or chlorine 10 15 ppm, 30
minutes
Stable to treatment with 20%
ether, acid (pH 1.0
for 2 hours)
Infectivity can be preserved

LABORATORY DIAGNOSIS
Virus particles have been detected
by immune electron microscopy in
fecal extracts of
hepatitis A patients
Virus appears early in the disease,
and disappears
within 2 weeks
following onset
of jaundice
HAV can be detected in the liver,
stool, bile, and
blood of naturally
infected humans and experimental

Serology :
IgM specific anti-HAV fraction appears
during the acute phase peaking about
2
weeks after elevation of liver enzyme
Anti-HAV IgM usually decline to
undetectable levels within 3 6 months
Anti-HAV IgG appears soon after the
onset of the disease and eventually
replace IgM
IgG persist for decades
Methods for measuring Ab :
RPHA
ELISA
R I A

IMMUNOLOGIC AND BIOLOGIC

EVENTS ASSOCIATED WITH HAV
INFECTION
Jaundice
Ig
M
Aminotransferases
Ig
G

VIF
VIB
0

Weeks after exposure

VIF=virus in feces
VIB=virus in blood

10

12

HEPATITIS B VIRUS
(HBV)
Discovered by Blumberg
(1923)
Patients & aborigin
Australian Ag.
Cause serum hepatitis
Australian antigen

HBV Morphology
Structure & antigen
complex
3 shapes in serum
. Dane particles : 42
nm
. Spherical particles :
22 nm
. Filament particles :
22 nm

Hepatitis B virus particle

Virion 42 nm
HBsAg / Dane
particle

Nucleus
virion 28 nm
HBcAg

Lysis nucleus
virion (HBeAg)

Antigen structure :
1. HBsAg
HBs

Anti-

2. HBcAg
HBc

Anti-

STABILITY
Temperature 20oC more than
20 years
Dry, 25oC stay for 1 week
Temperature 100oC, 1 minute
pH 2,4 for 6 hours
Sodium hypochlorite 5% for 3
minutes

Viral replication :
Attachment Uncoating
DNA within nucleus
(transcription) mRNA
(translation) RNA
(reverse transcription)
cDNA re enter to
previous cycle

Attachment

Reenter cycle
Uncoating

Host DNA repair

cccD
NA
Nucle
us

Cytoplasm

AAA
AAA
AAA

mRNA

Positivestrand
DNA
synthesis

Translati
on

Encapsidat
ion
3.5 kb
RNA
HBV replication cycle

Negativestrand
DNA
synthesis

MODE OF
TRANSMISSION
- Parenteral
- Mucosal (per oral &
sexual
contact)
- Vertically from

Laboratory examination
Isolation : cell culture
difficult
Diagnosis :
Serology (Ag Ab)
Transaminase enzyme
(LFT)
Histology (biopsy)
PCR (molecular)
Electron Microscopy

Prodrome,
Acute diseases
Incubation
period

Important
diagnosis
tests

HBsAg

Convalescence
Early

HBsAg

IgM-anti HBc
Anti HBs
IgG anti-HBc

Relative
concentration
of reactants

Anti-HBc

HBsAg
Level of
detection

ALT
Symptoms

Anti HBs

HBeAg

Month after
exposure

Anti-HBe

Clinical and serologic events occurring in patient with acute

hepatitis B infection

SEROLOGICAL INTERPRETATION OF HBV

Results

INFECTION
Interpretation

HBsAg (+)

Hepatitis B infection active, acute/ chronic

Anti-HBs (+)

Protection to reinfection (immunity)

HBsAg (-)

(+) after > 16 weeks, persist for years

Anti-HBc (+)

Might be HBV active infection

Anti-HBs (-)

Should be confirm IgM anti-HBc, 3 months

Total anti-HBc persist 5-6 years

HBeAg (+)

Infectious active hepatitis, acute / chroni

HBsAg (+)

Potential infectious

Anti-HBe (+)

Non infectious blood

Carrier state

Prevaccination screening hepatitis B

HBsAg (+)
Anti-HBs (-)
Anti-HBc (-/+)

HBsAg (-)
HBsAg (-)
Anti-HBs (-) Anti-HBs (+)
Anti-HBc (+) Anti-HBc (+/-)
Titer > 10 mU/ml

HBsAg (-)
HBsAg (-)
Anti-HBs (+)
Anti-HBs (-)
Anti-HBc (+/-) Anti-HBc (-)
Titer < 10 mU/ml

No
Vaccination

Postpone
No
vaccination vaccination

Booster

Vaccination

LFT
examination

Check
Measure titer
anti-HBs
anti-HBs
3-6 months

Measure titer
anti-HBs

Measure titer
anti-HBs

HEPATITIS C VIRUS (HCV)

NANB hepatitis virus

parenteral

1960 - 1980 blood screening for HBV

post transfusion hepatitis
First reported by HOUGHTON
&BRADLEY
using molecular
biology technique, and
virus
clone (1984 )
Family Flaviviridae
Genus Hep-C-virus
Mode of transmission
- Blood transfusion

Structure & composition

ssRNA genome 9.4 kb, positive
strand
6 genotype :
(1a,b, 2a,b,c, 3a,b, 4, 5 and 6)
enzyme specific to HCV &
essential
the
replication of the virus
Protease
RNA-dependent RNA

Pat hology
Clinical symptoms
mild
Elevation of liver
enzymes mild to
moderate
Disease develop to :
-Chronic infection

Laboratory diagnosis
Specimen : blood & liver biopsy
Microscopic : detection of virus
particle
Tissue culture : can not grow
Inoculation in chimpansee
Serology : antibody detection antiHCV (ELISA)
P C R : Molecular detection of
RNA virus

Treatment :
Interferon
Ribavirin : synthetic guanosine nucleoside
analog with activity against a number of
viruses

Ribavirin alone :
has only small effect on the
biochemical parameters of hepatic
function & replication of HCV
combination with IFN-2b

Hepatitis D Virus (HDV)

Reported first by RIZETTO,
CANESE &
ARICO
(1977)
Family?
Genus Deltavirus
Transmission : parenteral
parallel with
HBV
Develop to chronic

Structure & composition

Genome : ssRNA 1.7 kb, 35
37 nm
Delta antigen surrounding by
HBsAg
Defective virus, need hepatitis
B virus for replication

Hepatitis D virus particle surround

hepatitis B
virus particle

by

Hepatitis E virus(HEV)
NANB hepatitis virus
oral
Family Caliciviridae
Incubation period 3 7
weeks

Structure &
composition
Genome ssRNA
7.5 kb
32 34 nm
Positive strand
Envelope
Heat stable

Laboratory diagnosis
Specimen : stool and liver
biopsy
Electron microscopy :
detection of virus particle
Serology : Specific antibody
in serum
fluorescence

Hepatitis F Virus
(HFV)
Reported in France at
1997
Morphology

unclea
r

Hepatitis G virus(HGV)
The

newest virus identified

Reported at 1995 1996
Family Flaviviridae
3 genotype :
GB-A
plant viruses
GB-B
GB-C
human virus

Morphology :
- Genome RNA positive-strand,
2900 bp
enzyme : RNA polimerase;
Helicase ; Protease
Mode of transmission
parenteral
- Blood transfusion
- Transplantation
- Sexual contact (probably)
Might be single infection or
with HBV/ HBC

Laboratory diagnosis
P C R : molecular
EM : virus particle
Serology : antibody
test
under
development

T T Virus
Reported in Japan, 1997
Hepatitis post transfusion
New classification of virus
Family Circinoviridae
Similar with Circinoviridae :
palnts &
vertebrates
Morphology :
DNA virus ss linear, size30 50
nm
Non envelope, 3739 nucleotide
Fulminant hepatitis : chronic

Kepustakaan
1.Jawetz
2.Boyd
3.Human Virology Leslie Collier
and Jhons Oxford