REFERENCE

Knipe, D. M. and P. M. Howley, Eds. (2001). Field' Virology.

Philadelphia, Lippincott Williams & Wilkins.
Viral Hepatitis
Differential Features
Features Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E
Genome type Ss RNA Ds DNA Ss RNA Ss RNA Ss RNA

Familiy Picornaviridae Hepadnavirida Flaviviridae Deltaviridae Clciviridae

e
Genome size 7.5 kB 3.2 kB 9.4 kB 1.7 kB 7.5 kB

Incubation 15-49 (30) 28-160 15-160 21-140 15-65 (42)

period, days (70-80) (50) (35)
(mean)
Fecal-oral yes no no no yes
transmission
Parenteral rare yes yes yes no
transmission
Sexual no yes, common yes, yes, no
transmission uncommon uncommon
Fulminant <1% <1% rare 2-7.5% ~1%, 30% in
hepatitis pregnancy
Chronic no 10% 85% 90% with no
hepatitis superinfection
Hepatitis Virus A
 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)
Resisten etanol 70%, isopropanolol, dilute lysol, ammonium
compound
Hepatitis A - Clinical Features
Incubation period: Average 30 days
Range 15-50 days

Jaundice by <6 yrs, <10%

age group: 6-14 yrs, 40%-50%
>14 yrs, 70%-80%

Complications: Fulminant hepatitis

Cholestatic hepatitis
Relapsing hepatitis
Chronic sequelae: None
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.
Viral Hepatitis
5 types:
A: fecal-oral transmission
B: sexual fluids & blood to blood
C: blood to blood
D: travels with B Vaccine
Preventable
E: fecaloral transmission
Adapted from Corneil, 2003
 Hepatitis A Vaccination
Strategies
Epidemiologic
Considerations
Persons at increased risk of infection
travelers
homosexual men
injecting drug users
Person who work with HAV
Person residing in area where extended
community outbreak exist
Hepatitis B Virus
FUSION OF HBV
 Hepatitis B - Clinical
Features
Incubation period: Average 60-90 days
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%
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.
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.
 Concentration of Hepatitis B
Virus in Various Body Fluids

Low/Not
High Moderate Detectable

blood semen urine

serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
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 C Virus
 HCV is a member of flavivirus family.
HCV genome is a single stranded positive-
sense RNA and contains 9.4kb
Antigen-antibody system
The concentration of HCV in blood is low,
HCV Ag has not be detected, anti-HCV is the
indicator of infection and the marker of
infectivity
HCV-RNA
HCV-RNA may be detected from blood or liver
tissue, its the direct evidence of infectivity
 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
 Hepatitis C Virus Infection
Typical Serologic Course
anti-
HCV
Symptom
s

Titr
e

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4
Month Years
s
Time after
Exposure
 Risk Factors
Associated with
Transmission
Transfusion of infected
or transplant from HCV 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.
 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 Virus
Modes of
Transmission
Percutanous exposures
injecting drug use
Permucosal exposures
sex contact
 HBV - HDV
Coinfection
Symptoms Typical Serologic
ALT
Course
Elevated
Titre
anti-HBs
IgM anti-HDV

HDV RNA

HBsAg
Total anti-HDV

Time after
 HBV - HDV
Superinfection
Typical Serologic
Course
Jaundice

Symptoms

Total anti-HDV
ALT
Titre

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: Average 40 days
Range 15-60 days
Case-fatality rate: Overall, 1%-3%
Pregnant women,
15%-25%
Illness severity: Increased
with age
Chronic sequelae: None identified
 Hepatitis E Virus
Infection
Symptom
Typical s
Serologic ALT IgG anti-HEV
Course

Titer IgM anti-HEV

Virus in stool

0 1 2 3 4 5 6 7 8 9 1 1 1 1
0 1 2 3
Weeks after
 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?
Baltimore classification

The Baltimore Classification of viruses is based on the

method of viral mRNA synthesis.