University of sulaimani

Collage of science
Department of biology
SIMINAR ABOUT :

Hepatitis virus
Prepared by:
Abubakr Sdiq Sargaty

Hepatitis virus

Overview of Hepatitis Virus

Virus

Virus group

Nucleic
acid

Mode of infection

Severity
(chronicity)

HAV

Enterovirus
72(heptovirus)

RNA

Fecal-oral

+(acute)

HBV

hepadnavirus

DNA

Percutaneous;
Permucosal

++(chronic)

HCV

Flavivirus

RNA

Blood(transfusionassociated)

+ (chronic)

HDV

B-dependent
small virus

RNA

blood

+ (chronic)

HEV

Calicivirus

RNA

Fecal-oral

+(acute)

HGV

RNA

Blood

Viral Hepatitis - Overview

Type of Hepatitis

A
Source of
virus
Route of
transmission
Chronic
infection
Prevention

feces

blood/
blood/
blood/
blood-derived blood-derived blood-derived
body fluids
body fluids
body fluids

feces

fecal-oral

percutaneous percutaneous percutaneous

permucosal
permucosal
permucosal

fecal-oral

no

yes

pre/postexposure
immunization

pre/postexposure
immunization

yes

yes

blood donor
pre/postscreening;
exposure
risk behavior immunization;
modification risk behavior
modification

no
ensure safe
drinking
water

Human cytomegalovirus

Epstein-Barr virus

Herpes simplex virus

Yellow fever virus

Rubella.

Hepatitis A virus

Structure

Small, nonenveloped
icosahedral
particle,
27 nm in
diameter
ssRNA

Replication

Unlike other picornaviruses, however, HAV is not

cytolytic and is released by exocytosis.
Laboratory isolates of HAV have been adapted to
growth in primary and continuous monkey kidney cell
lines, but clinical isolates are very difficult to grow in
cell culture.

Resistance
Stable to:
acid at pH 3
Solvents(ether,chloroform)
detergents
saltwater,groundwater(months)
drying(stable)
temperature
4: weeks
56for 30minutes: stable
61for 20minutes: partial inactivation

Resistance
Inactivated by:
chlorine treatment of drinking water
formalin(0.35%,37,72hours)
acetic acid(2%,4hours)
B-propiolactone (0.25%,1hours)
Ultraviolet radiation(2W/ 2/min)

Hepatitis A Virus Transmission

Virus can be transmitted via fecal-oral route

ingestion of contaminated food and water can
cause infection
HAV in shellfish is from sewage-contaminated
water
Virus can be transmitted by food handlers, daycare workers, and children.

Body Fluid

Concentration of Hepatitis A Virus

in Various Body Fluids
Feces

Serum
Saliva

Urine

100

102

104

106

Infectious Doses per

ml
Source: Viral Hepatitis and Liver Disease 1984;9-22
J Infect Dis 1989;160:887-890

108

1010

Geographic Distribution of HAV

Infection

Anti-HAV Prevalence
High
Intermediate
Low
Very Low

Age-specific Mortality Due to

Hepatitis A
Age group
(years)

<5
5-14
15-29
30-49
>49
Total

Case-Fatality
(per 1000)

3.0
1.6
1.6
3.8
17.5
4.1

Source: Viral Hepatitis Surveillance Program, 1983-1989

Hepatitis A - Clinical
Features
Average 30 days
Incubation period
Jaundice by
age group

Range 15-50 days

<6 yrs

<10%

6-14 yrs

40%-50%

>14 yrs

70%-80%

Hepatitis A - Clinical Features

Milder disease than Hepatitis B;

asymptomatic infections are very common,
especially in children.
Adults, especially pregnant women, may develop
more severe disease
no chronic form of the disease.
Complications:
Fulminant hepatitis is rare: 0.1% of cases

Pathogenesis

Pathogenesis of HAV

HAV replicates slowly in the liver without

producing apparent cytopathological effects
(CEPs). In the absence of cytolysis, the virus
readily establishes a persistent infection.
Jaundice, resulting from damage to the liver
Antibody is detected and cell-mediated immune
responses to the virus

For example

An epidemic of HAV that occurred in Shanghai, China,

in 1988 in which 300,000 people were infected with the
virus resulted from eating Anadara subcrenata
obtained from a polluted river.

Time course of HAV infection

Immunity

Antibody protection against reinfection is lifelong

Laboratory Diagnosis

Viral particles in the stool, by electron microscopy

Specific IgM in serum

PCR HAV-specific sequences in stool

Treatment, Prevention and Control

Prophylaxis with immune serum globulin given before

or early in the incubation period

A killed HAV vaccine has been approved and is

available for use in children and adults at high risk for
infection.

A live HAV vaccine has been developed in China.

Hepatitis B virus

Introduction

approximately 350 million people are infected

globally with HBV.

Structure

Small, enveloped DNA

The genome: a small, circular, partly double-stranded

DNA of 3200 base

Although a DNA virus, it encodes a reverse transcriptase

and replicates through an RNA intermediate.

Structure

Dane particle, is 42 nm in
diameter.
Resist to treatment with: ether, a
low pH, freezing, and moderate
heating. This helps transmission
from one person to another.

Decoy Particles

HBsAg-containing particles
are released into the serum of
infected people and
outnumber the actual virions.
Spherical or filamentous
They are immunogenic and
were processed into the first
commercial vaccine against
HBV.

Structure

HBcAg HBsAg HBeAg

42nm
HBsAg

15-25nm

2020200nm

28nm
HBcAg
DNA
HBeAg

Replication

HBV has a very defined tropism for the liver.

Its small genome also necessitates economy, as
illustrated by the pattern of its transcription and
translation.
In addition, HBV replicates through an RNA
intermediate and produces and release antigenic
decoy particles.

Replication

The entire genome can also be integrated into the host

cell chromatin.
HBsAg, but not other proteins, can often be detected in
the cytoplasm of cells containing integrated HBV DNA.
The significance of the integrated DNA in the replication
of the virus is not known, but integrated viral DNA has
been found in hepatocellular carcinomas.

Global Patterns of Chronic HBV Infection

High (>8%): 45% of global population

lifetime risk of infection >60%
early childhood infections common
Intermediate (2%-7%): 43% of global population
lifetime risk of infection 20%-60%
infections occur in all age groups
Low (<2%): 12% of global population
lifetime risk of infection <20%
most infections occur in adult risk groups

High-risk groups for HBVinfection

People from endemic regions

Babies of mothers with chronic HBV
Intravenous drug abusers
People with multiple sex partners
Hemophiliacs and other patients requiting blood
and blood product treatments
Health care personnel who have contact with blood
Residents and staff members of institutions for the
mentally retarded

Concentration of Hepatitis B
Virus
in Various Body Fluids
High

Blood ,Serum,Wound exudates

Moderate

Semen, vaginal and menstrual

secretions, Saliva, amniotic fluid

Low/Not
Detectable

Urine , Feces, Sweat , Tears ,

Breast milk

What determines the development of chronic vs.

acute infection

Age (chronic infections decrease with increasing age)

Sex:
Syndrome:
Males : Females
Chronic Infection:
1.5 : 1
Cirrhosis:
3:1
PHC:
6:1
Route of infection (oral/sexual infections give rise to
less chronic cases than serum infection

Hepatitis B - Clinical
Features
Incubation period:
days

Average 60-90

Range 45-180 days

Clinical illness (jaundice): <5 yrs, <10%
5 yrs, 30%-50%
Acute case-fatality rate:
0.5%-1%
Chronic infection:
<5 yrs, 30%-90%
5 yrs, 2%-10%
Premature mortality from
chronic liver disease:
15%-25%

80

80

60

60

Chronic Infection

40

40

20

20
Symptomatic Infection

0
Birth

1-6 months

7-12 months

Age at Infection

1-4 years

0
Older Children
and Adults

Symptomatic Infection (%)

Chronic Infection (%)

Outcome
of Hepatitis B Virus Infection
100
100
by Age at Infection

Pathogenesis(1)

The virus starts to replicate within 3 days of its

acquisition,
Symptoms may not be observed for 45 days of
longer, depending on the infectious dose, the
route of infection, and the person.

Pathogenesis(2)

Hypoimmune response.
IFN,HLA-ICTL(An insufficient T-cell response )
Cell mediated immunopathogenic damage.
CTL acute hepatitis/chronic hepatitis

Pathogenesis (3)

Immune complexes formed between HBsAg and antiHBs contribute to the development of hypersensitivity
reactions, leading to problems such as vasculitis ,
arthralgia , rash, and renal damage.

Pathogenesis(4)

Pathogenic damage caused by autoimmunity

liver specific protein(LSP)
Viral variation
HBeAg

Clinical Syndromes

Major
eterminants of
acute and chronic
HBV infection

Acute Infection

Symptoms of Acute Infection

Clinical
outcomes of
acute
hepatitis B
infection

The serological events associated with the typical course of acute

HBV disease

Typical Serologic Course

Acute Hepatitis B Virus Infection with
Recovery
Symptoms

anti-HBe

HBeAg

Total anti-HBc

Titer

anti-HBs

IgM anti-HBc

HBsAg

12

16

20

24

28

Weeks after

32

36

52

100

Chronic Infection

Chronic hepatitis occurs in 5% to 10% of people

with HBV infections, usually after mild or
inapparent initial disease.
Detected by the finding of elevated liver enzyme
levels

Development of the chronic HBV carrier state

Typical Serologic Course

Progression to Chronic HBV Infectio

Acute
(6 months)

Chronic
(Years)
HBeAg

anti-HBe
HBsAg
Total anti-HBc

Titer

IgM anti-HBc

8 12 16 20 24 28 32 36

52

Weeks after Exposure

Years

Primary Hepatocellular Carcinoma

The WHO estimates that 80% of all cases of

PHC can be attributed to chronic HBV
infections.
HBV may induce PHC by promoting continued
liver repair and cell growth in response to
tissue damage or by integrating into the host
chromosome and stimulating cell growth
directly.

Lab. Diagnosis

The initial diagnosis of hepatitis can be made on

the basis of the clinical symptoms and the
presence of liver enzymes in the blood.
The serology of infection describes the course
and the nature of the disease.
Acute and chronic HBV infect. Can be
distinguished by the presence of HBsAg and
HBeAg in the serum and the pattern of Ab to the
individual HBV antigens.

Diagnosis

During the symptomatic phase of infection,

detection of antibodies to HBeAg and HBsAg is
obscured because the antibody is complexed
with antigen in the serum.
The best way to diagnose a recent acute
infection, especially during the period when
neither HBsAg nor anti-HBs can be detected, is
to measure IgM anti-HBc.

Diagnosis

Detection of serum HBVDNA: nucleic

hybridization; PCR.
Detection of viral DNA polymerase.

Treatment

Interferon-alpha may be effective for treating

a chronic HBV infection.
Hepatitis B immune globulin may be
administered within a week of exposure and to
newborn infants of HBsAg-positive mothers.

Elimination of Hepatitis B Virus

Transmission

Objectives
Prevent chronic HBV Infection
Prevent chronic liver disease
Prevent primary hepatocellular
carcinoma
Prevent acute symptomatic HBV
infection

Elimination of Hepatitis B Virus

Transmission

Strategy

Prevent perinatal HBV

transmission
Routine vaccination of all infants
Vaccination of children in high-risk groups
Vaccination of adolescents
all unvaccinated children at 11-12 years
of age
high-risk adolescents at all ages
Vaccination of adults in high-risk groups


HBsAg

HBeAg

- HBs

- HBe

- HBc

HBV

Hepatitis C Virus

Introduction

The major cause of parenterally transmitted

non A non B hepatitis. It eluded identification
for many years. In 1989, the genome was
cloned from the serum of an infected
chimpanzee.

Features of Hepatitis C Virus Infection

Incubation period
Acute illness (jaundice)
Case fatality rate
Chronic infection
Chronic hepatitis
Cirrhosis
Mortality from CLD
(chronic liver disease )

Average 6-7 weeks

Range 2-26 weeks
Mild (<20%)
Low
75%-85%
70% (most asx)
10%-20%
1%-5%

Common characteristics

Putative Togavirus related to the Flavi and

Pesti viruses.Thus probably enveloped.

Has a ssRNA genome

Does not grow in cell culture, but can infect

Chimpanzees

Transmission

Blood transfusions, blood products

organ donation
Intravenous drug abusers
community acquired: mechanism unclear. ?
Vertical transmission ?
sexual intercourse

Epidemiology

Causes a milder form of acute hepatitis than

does hepatitis B
But 50% individuals develop chronic infection,
following exposure.
Incidence endemic world-wide; high incidence
in Japan, Italy and Spain

Clinical syndromes

HCV can cause acute infections but is more

likely to establish chronic infections.
Viremia
Chronic persistent hepatitis
Chronic active hepatitiw
Cirrhosis
Liver failure

Chronic Hepatitis C
Factors Promoting Progression or Severity

Increased alcohol intake

Age > 40 years at time of infection

HIV co-infection

?Other

Male gender
Other co-infections (e.g., HBV)

Serologic Pattern of Acute HCV Infection

with Recovery
anti-HCV
Symptoms +/-

Titer

HCV RNA

ALT

Normal
0

3
4
Months

Time after Exposure

2
3
Years

Serologic Pattern of Acute HCV Infection with

Progression to Chronic Infection
anti-HCV
Symptoms +/-

Titer

HCV RNA

ALT

Normal
0

3
4
Months

Time after Exposure

2
3
Years

HCV Prevalence by Selected Groups

United States
Hemophilia
Injecting drug users
Hemodialysis
STD clients
Gen population adults
Surgeons, PSWs
Pregnant women
Military personnel

10

20
30
40
50
60
70
80
Average Percent Anti-HCV Positive

90

Laboratory diagnosis

1) Serology
Reliable serological tests have only recently
become available.
HCV-specific IgG indicates exposure, not
infectivity
2) PCR detects viral genome in patient's serum

Treatment, Prevention, and Control

Recombinant interferon-alpha is the only

known effective treatment for HCV.
Illicit drug abuse and transfusion are the most
identifiable sources of HCV viruses.

Hepatitis D virus

Introduction

Defective virus which requires Hepatitis B virus

as a helper virus in order to replicate. Infection
only occurs in patients who are already infected
with Hepatitis B.

Structure

Virus particle 36
nm in diameter
encapsulated with
HBsAg, derived
from HBV
Delta antigen is
associated with
virus particles
ssRNA genome

Hepatitis D (Delta) Virus

antigen

HBsAg

RNA

Replication

Transcription and replication of the HDV

genome are unusual. Specifically, the host cells
RNA polymerase II makes an RNA copy,
replicates the genome, and makes mRNA.

Geographic Distribution of HDV Infection

Taiwan
Pacific Islands

HDV Prevalence
High
Intermediate
Low
Very Low
No Data

Pathogenesis

Spread in blood, semen, and vaginal secretion.

It can replicate and cause disease only in
people with active HBV infections.
Replication of the delta agent results in
cytotoxicity and liver damage.

Clinical Syndromes

Increases the severity of HBV infections.

Fulminant hepatitis

Hepatitis D - Clinical
Features
Coinfection
severe acute disease
low risk of chronic infection
Superinfection
usually develop chronic HDV infection
high risk of severe chronic liver
disease

HBV - HDV Coinfection

Symptoms

Typical Serologic Cours

Titer

ALT
Elevated

IgM antiHDV

antiHBs

HDV RNA
HBsAg
Total antiHDV

Time after
Exposure

HBV - HDV Superinfection

Jaundice

Typical Serologic Course

Symptoms
Total anti-HDV

Tite
r

ALT

HDV RNA
HBsAg
IgM anti-HDV

Time after

Laboratory Diagnosis

Detect the delta antigen of antibodies

ELISA and RIA

Hepatitis D - Prevention
HBV-HDV Coinfection
Pre or postexposure prophylaxis to
prevent HBV infection
HBV-HDV Superinfection
Education to reduce risk behaviors
among persons with chronic HBV
infection

Hepatitis E Virus

Structure and Genome

30-32nm non-enveloped particle

s/s (+)sense RNA genome , ~7.5Kb.
Genetic organization similar (not identical) to
Caliciviruses

Hepatitis E - Clinical
Features
Incubation period:

Average 40 days
Range 15-60 days

Case-fatality rate:
Overall, 1%-3%
Pregnant women, 15%-25%
Illness severity:
Chronic sequelae:

Increased with age

None identified

Geographic Distribution of
Hepatitis E

Hepatitis E Epidemiologic Features

Most outbreaks associated with
fecally contaminated drinking
water
Minimal person-to-person
transmission

Prevention and Control Measures

for Travelers to HEV-Endemic
Regions
Avoid drinking water (and beverages with
ice) of unknown purity, uncooked shellfish,
and uncooked fruit/vegetables not peeled or
prepared by traveler
IG prepared from donors in Western
countries does not prevent infection
Unknown efficacy of IG prepared from donors
in endemic areas
Vaccine?

Epidemiology

The delta agent infects children and adults

with underlying HBV infection, and people
who are persistently infected with both HBV
and HDV are a source for the virus.