Hepatitis A-E Viruses

An Overview
 Viral Hepatitis - Historical Perspectives

“ Infectious” A Enterically
E
transmitted

Viral NANB
hepatitis

Parenteral
“ Serum” B D C ly
transmitte
F, G, TTV
d
? other
 Type of Hepatitis
A B C D E

Source of feces blood/ blood/ blood/ feces

virus blood-derived blood-derived blood-derived
body fluids body fluids body fluids

Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral

transmission permucosal permucosal permucosal

Chronic no yes yes yes no

infection

Prevention pre/post- pre/post- blood donor pre/post- ensure safe

exposure exposure screening; exposure drinking
immunization immunization risk behavior immunization; water
modification risk behavior
modification
Hepatitis A Virus
 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
 Hepatitis A Infection
Typical Serological Course

Symptom Total anti-

s HAV

Titre ALT

Fecal
HAV
IgM anti-HAV

0 1 2 3 4 5 6 1 2
2 4
Months after exposure
 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 Transmission Patterns

High Low to Early Person to person;

High childhood outbreaks uncommon
Moderate High Late Person to person;
childhood/ food and waterborne
young adults outbreaks
Low Low Young adults Person to person;
food and waterborne
outbreaks
Very low Very low Adults Travelers; outbreaks
uncommon
 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 and high
HAV-endemic regions
 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: 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%
 Premature mortality from
chronic liver disease: 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

Symptoms
HBeAg anti-HBe

Total anti-HBc
Titre

HBsAg IgM anti-HBc anti-HBs

0 4 8 12 16 20 24 28 32 36 52 100

Weeks after
Progression to Chronic Hepatitis B Virus
Infection
Acute Chronic
(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 52 Years
Weeks after Exposure
 Outcome of Hepatitis B Virus
100 Infection 100
by Age at Infection
80
Chronic Infection (%)

80

Symptomatic Infection (%)

60 60
Chronic Infection

40 Chronic Infection (%) 40

20 20

Symptomatic Infection
0 0
Birth 1-6 months 7-12 months 1-4 years Older Children
and Adults
Age at Infection
 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
 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
 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 protease/heli RNA- RNA

pe case dependent polymerase
protei
c2 n 33c c-
2 100
5’ 3’

cor E1 E2 NS NS NS NS
e 2 3 4 5

hypervariable
region
 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

anti-
HCV
Symptom
s

Titre

ALT

Norma
l
0 1 2 3 4 5 6 1 2 3 4
Mont Years
hsTime
after Exposure
 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 anti-
HDV

HDV RNA

HBsAg
Total anti-HDV

Time after Exposure

 HBV - HDV
Coinfection
Symptoms

ALT Elevated

Titre
anti-
IgM anti- HBs
HDV

HDV RNA

HBsAg
Total anti-
HDV

Time after Exposure

 HBV - HDV
Superinfection
Jaundice

Symptoms

Total anti-HDV
ALT
Titre

HDV RNA
HBsAg

IgM anti-HDV

Time after Exposure

 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
s

ALT IgG anti-HEV

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 Exposure
 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?