Hepatitis A-E Viruses: Ni Putu Galuh Wibhutisari (10-169)

HEPATITIS A-E
VIRUSES
Ni Putu Galuh Wibhutisari
Viral Hepatitis - Historical Perspectives

Infectious
Viral
hepatitis
Serum
Enterically
E
transmitted
NANB
Parenteral
B D
C ly
transmitte
F, G, TTV
d
? other
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
pre/postexposure
immunization
yes
yes
yes
pre/postblood donor
pre/postexposure
screening;
exposure
immunization risk behavior immunization;
modification risk behavior
modification
no
ensure safe
drinking
water
Hepatitis A Virus
Hepatitis A - Clinical Features
Incubation period:
Jaundice by
age group:
Complications:
Chronic sequelae:
Average 30 days
Range 15-50 days
<6 yrs, <10%
6-14 yrs, 40%-50%
>14 yrs, 70%-80%
Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
None
Hepatitis A Infection
Typical Serological Course
Total antiHAV
Symptom
s
Titre
ALT
Fecal
HAV
IgM anti-HAV
Months after exposure
1
2
2
4
Hepatitis A Virus Transmission
Close personal contact

(e.g., household contact, sex contact, child day
care centers)
Contaminated food, water

(e.g., infected food handlers, raw shellfish)
Blood exposure (rare)

(e.g., injecting drug use, transfusion)
Global Patterns of
Hepatitis A Virus Transmission
Disease Peak Age
Endemicity
Rate of Infection
High
Transmission Patterns
Low to
High
Early
childhood
Person to person;
outbreaks uncommon
Moderate
High
Late
childhood/
young adults
Person to person;
food and waterborne
outbreaks
Low
Low
Young adults
Very low
Adults
Person to person;
food and waterborne
outbreaks
Travelers; outbreaks
uncommon
Very low
Laboratory Diagnosis
Acute infection is diagnosed by the detection of

HAV-IgM in serum by EIA.
Past Infection i.e. immunity is determined by the

detection of HAV-IgG by EIA.
Hepatitis A Vaccination
Strategies
Epidemiologic Considerations
Many cases occur in community-wide outbreaks
no risk factor identified for most cases

highest attack rates in 5-14 year olds
children serve as reservoir of infection
Persons at increased risk of infection
travelers
homosexual men
injecting drug users
Hepatitis A Prevention Immune Globulin
Pre-exposure
travelers
to
intermediate
HAV-endemic regions
and
high
Post-exposure (within 14 days)

Routine
household and other intimate contacts
Selected situations
institutions (e.g., day care centers)
common source exposure (e.g., food prepared by
infected food handler)
Hepatitis B Virus
Hepatitis B - Clinical
Features
Incubation period:
Clinical illness (jaundice):
Acute case-fatality rate:
Chronic infection:
Premature mortality from
chronic liver disease:
Average 60-90 days

Range 45-180 days
<5 yrs, <10%
5 yrs, 30%-50%
0.5%-1%
<5 yrs, 30%-90%
5 yrs, 2%-10%
15%-25%
Spectrum of Chronic Hepatitis B Diseases
1. Chronic Persistent Hepatitis - asymptomatic

2. Chronic Active Hepatitis - symptomatic
exacerbations of hepatitis
3. Cirrhosis of Liver
4. Hepatocellular Carcinoma
Acute Hepatitis B Virus Infection with

Recovery
Typical Serologic
Course
Symptoms
anti-HBe
HBeAg
Total anti-HBc
Titre
anti-HBs
IgM anti-HBc
HBsAg
12 16 20 24 28 32 36
Weeks after
52
100
Progression to Chronic Hepatitis B Virus

Infection Typical Serologic
Acute
Chronic
Course
(6 months)
(Years)
HBeAg
anti-HBe
HBsAg
Total anti-HBc
Titr
e
IgM anti-HBc
0 4 8 12 16 20 24 28 32 36
Weeks after
52
Years
80
60
40
Chronic Infection
100
80
60
40
Chronic Infection (%)
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 (%)
100
Outcome of Hepatitis B Virus

Infection
by Age at Infection
Global Patterns of Chronic

HBV Infection
High (>8%): 45% of global population
Intermediate (2%-7%): 43% of global population
lifetime risk of infection >60%

early childhood infections common
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
Concentration of Hepatitis B
Virus in Various Body Fluids
High
Moderate
blood
serum
wound exudates
semen
vaginal fluid
saliva
Low/Not
Detectable
urine
feces
sweat
tears
breastmilk
Hepatitis B Virus
Modes of Transmission
Sexual - sex workers and homosexuals are
particular at risk.
Parenteral - IVDA, Health Workers are at
increased risk.
Perinatal - Mothers who are HBeAg positive are
much more likely to transmit to their offspring
than those who are not. Perinatal transmission is
the main means of transmission in high
prevalence populations.
Diagnosis
A battery of serological tests are used for the diagnosis of acute and
chronic hepatitis B infection.
HBsAg - used as a general marker of infection.
HBsAb - used to document recovery and/or immunity to HBV
infection.
anti-HBc IgM - marker of acute infection.
anti-HBcIgG - past or chronic infection.
HBeAg - indicates active replication of virus and therefore
infectiveness.
Anti-Hbe - virus no longer replicating. However, the patient can still
be positive for HBsAg which is made by integrated HBV.
HBV-DNA - indicates active replication of virus, more accurate than
HBeAg especially in cases of escape mutants. Used mainly for
monitoring response to therapy.
Treatment
Interferon - for HBeAg +ve carriers with chronic active

hepatitis. Response rate is 30 to 40%.
Lamivudine - a nucleoside analogue reverse transcriptase

inhibitor. Well tolerated, most patients will respond
favorably. However, tendency to relapse on cessation of
treatment. Another problem is the rapid emergence of drug
resistance.
Successful response to treatment will result in the

disappearance of HBsAg, HBV-DNA, and seroconversion
to HBeAg.
Prevention
Vaccination - highly effective recombinant vaccines are now

available. Vaccine can be given to those who are at increased
risk of HBV infection such as health care workers. It is also
given routinely to neonates as universal vaccination in many
countries.
Hepatitis B Immunoglobulin - HBIG may be used to protect

persons who are exposed to hepatitis B. It is particular
efficacious within 48 hours of the incident. It may also be given
to neonates who are at increased risk of contracting hepatitis B
i.e. whose mothers are HBsAg and HBeAg positive.
Other measures - screening of blood donors, blood and body

fluid precautions.
Hepatitis C Virus
capsid envelo
pe
protei
c2
n
2
protease/heli
case
33
c
RNARNA
dependent polymerase
c100
3
cor E1
e
E2
hypervariable
region
NS
2
NS
3
NS
4
NS
5
Hepatitis C - Clinical
Features
Incubation period:
Average 6-7 wks

Range 2-26 wks
Clinical illness (jaundice):
30-40% (20-30%)
Chronic hepatitis:
70%
Persistent infection:
85-100%
Immunity:
No protective
antibody
response identified
Chronic Hepatitis C
Infection
The spectrum of chronic hepatitis C infection is

essentially the same as chronic hepatitis B
infection.
All the manifestations of chronic hepatitis B

infection may be seen, albeit with a lower
frequency i.e. chronic persistent hepatitis, chronic
active hepatitis, cirrhosis, and hepatocellular
carcinoma.
Hepatitis C Virus Infection

Typical Serologic Course
antiHCV
Symptom
s
Titr
e
ALT
3 4
Mont
hsTime
Norma
l
5 6 1
after
Exposure
2 3
Years
Risk Factors
Associated with
Transmission of HCV
Transfusion or transplant from infected donor
Injecting drug use
Hemodialysis (yrs on treatment)
Accidental injuries with needles/sharps
Sexual/household exposure to anti-HCV-positive
contact
Multiple sex partners
Birth to HCV-infected mother
Laboratory Diagnosis
HCV antibody - generally used to diagnose hepatitis C

infection. Not useful in the acute phase as it takes at least 4
weeks after infection before antibody appears.
HCV-RNA - various techniques are available e.g. PCR and

branched DNA. May be used to diagnose HCV infection in
the acute phase. However, its main use is in monitoring the
response to antiviral therapy.
HCV-antigen - an EIA for HCV antigen is available. It is

used in the same capacity as HCV-RNA tests but is much
easier to carry out.
Treatment
Interferon - may be considered for patients with

chronic active hepatitis. The response rate is
around 50% but 50% of responders will relapse
upon withdrawal of treatment.
Ribavirin - there is less experience with ribavirin

than interferon. However, recent studies suggest
that a combination of interferon and ribavirin is
more effective than interferon alone.
Prevention of
Hepatitis C
Screening of blood, organ, tissue donors
High-risk behavior modification
Blood and body fluid precautions
Hepatitis D (Delta)
antigenVirus
HBsAg
RNA
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.
may present as an acute hepatitis.
Hepatitis D Virus
Modes of
Transmission
Percutanous exposures
injecting drug use
Permucosal exposures
sex contact
HBV - HDV
Coinfection
Symptoms
ALT
Elevated
Titre
anti-HBs
IgM antiHDV
HDV RNA
HBsAg
Time after
Total anti-HDV
HBV - HDV
Coinfection
Symptoms
ALT
Elevated
Titre
IgM antiHDV
antiHBs
HDV RNA
HBsAg
Total antiHDV
Time after
HBV - HDV
Typical Serologic
Superinfection
Course
Jaundice
Symptoms
Titre
Total anti-HDV
ALT
HDV RNA
HBsAg
IgM anti-HDV
Time after
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
Hepatitis E - Clinical Features
Incubation period:
Case-fatality rate:
Average 40 days
Range 15-60 days
Overall, 1%-3%
Pregnant women,
15%-25%
Illness severity:
Increased with age
Chronic sequelae:
None identified
Hepatitis E Virus Infection

Typical Serologic
Course Symptom
s
IgG anti-HEV
ALT
Titer
IgM anti-HEV
Virus in stool
Weeks after
1
0
1
1
1
2
1
3
Hepatitis E Epidemiologic
Features
Most outbreaks associated with faecally contaminated drinking

water.
Several other large epidemics have occurred since in the Indian
subcontinent and the USSR, China, Africa and Mexico.
In the United States and other nonendemic areas, where
outbreaks of hepatitis E have not been documented to occur, a
low prevalence of anti-HEV (<2%) has been found in healthy
populations. The source of infection for these persons is
unknown.
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?
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HEPATITIS A-E

Ni Putu Galuh Wibhutisari

Viral Hepatitis - Historical Perspectives

percutaneous percutaneous percutaneous

Hepatitis A - Clinical Features

Months after exposure

Hepatitis A Virus Transmission

Close personal contact

Contaminated food, water

Blood exposure (rare)

Acute infection is diagnosed by the detection of

Past Infection i.e. immunity is determined by the

Many cases occur in community-wide outbreaks

no risk factor identified for most cases

Persons at increased risk of infection

Hepatitis A Prevention Immune Globulin

Post-exposure (within 14 days)

Average 60-90 days

Spectrum of Chronic Hepatitis B Diseases

1. Chronic Persistent Hepatitis - asymptomatic

Acute Hepatitis B Virus Infection with

Progression to Chronic Hepatitis B Virus

Chronic Infection (%)

Symptomatic Infection (%)

Chronic Infection (%)

Outcome of Hepatitis B Virus

Global Patterns of Chronic

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

Intermediate (2%-7%): 43% of global population

lifetime risk of infection >60%

Low (<2%): 12% of global population

lifetime risk of infection <20%

Interferon - for HBeAg +ve carriers with chronic active

Lamivudine - a nucleoside analogue reverse transcriptase

Successful response to treatment will result in the

Vaccination - highly effective recombinant vaccines are now

Hepatitis B Immunoglobulin - HBIG may be used to protect

Other measures - screening of blood donors, blood and body

Average 6-7 wks

Clinical illness (jaundice):

The spectrum of chronic hepatitis C infection is

All the manifestations of chronic hepatitis B

Hepatitis C Virus Infection

HCV antibody - generally used to diagnose hepatitis C

HCV-RNA - various techniques are available e.g. PCR and

HCV-antigen - an EIA for HCV antigen is available. It is

Interferon - may be considered for patients with

Ribavirin - there is less experience with ribavirin

Pre or postexposure prophylaxis to prevent

Hepatitis E - Clinical Features

Increased with age

Hepatitis E Virus Infection

Most outbreaks associated with faecally contaminated drinking

Prevention and Control

Avoid drinking water (and beverages with ice) of

IG prepared from donors in Western countries

Unknown efficacy of IG prepared from donors in

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