Viral hepatitis

1. Hepatitis A-G Viruses
Topic 40

2. A
“Infectious”
“Serum”
Viral hepatitis
transmitted
Parenterall
y
F, G, TTV
transmitted
? other
E Enterically
N A N B
B D C
Viral Hepatitis - Historical Perspectives

3. Source of
virus
feces blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
feces
Route of
transmission
fecal-oral percutaneous
permucosal
percutaneous
permucosal
percutaneous
permucosal
fecal-oral
Chronic
infection
no yes yes yes no
Prevention pre/post-
exposure
immunization
pre/post-
exposure
immunization
blood donor
screening;
risk behavior
modification
pre/post-
exposure
immunization;
risk behavior
modification
ensure safe
drinking
water
Type of Hepatitis
B C D E

5. Hepatitis A Virus

6. Hepatitis A Virus
 Naked RNA virus
 Formerly known as enterovirus 72, now it is
in its own family: heptovirus


One stable serotype only
Difficult to grow in cell culture: primary
marmoset cell culture and also in vivo in
chimpanzees and marmosets

7. Hepatitis A Virus….


 Survives well in the general
environment
Somewhat resistant to heat and
freezing
Remain active on the hands for several
hours or in food kept at room
temperature.

8. Hepatitis A can be transmitted:
 Through fecal-oral route



 by infected food handlers
in locations/sites with poor sanitation and hygiene
(e.g., in developing countries)
by poor hygiene standards
after natural disasters, such as floods, when
drinking water can become contaminated with
sewage
 during sex, particularly oral/anal sex

9. 


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)
Summary of Hepatitis A Virus
Transmission

10. Endemicity
Disease
Rate
Peak Age
of Infection Transmission Patterns
High
Moderate
Low to
High
High
Low
Early
childhood
Late
childhood/
young adults
Low Young adults
Very low Very low Adults
Person to person;
outbreaks uncommon
Person to person;
food and waterborne
outbreaks
Person to person;
food and waterborne
outbreaks
Travelers; outbreaks
uncommon
Global Patterns of
Hepatitis A Virus Transmission

11. Infective dose ….
 Infective dose not known
 But since hepatitis A is transmitted so
easily through person to person
contact, it is thought to be a small
amount

12.  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 - Clinical
Features

13. F e c a l
H AV
S y m p t o
m s
0 1 2 1
2
2
4
Hepatitis A Infection
Total anti-
HAV
Titre ALT
IgM anti-HAV
3 4 5 6
Months after exposure
Typical Serological Course

14. Laboratory Diagnosis




Acute infection : HAV-IgM in serum by EIA.
Past Infection i.e. immunity: HAV-IgG by EIA.
Cell culture – difficult and take up to 4 weeks,
not routinely performed
Direct Detection – EM, RT-PCR of faeces. Can
detect illness earlier than serology but rarely
performed.

15.  NO medical treatment available to treat the virus.


Symptoms of hepatitis A : can be relieved to some
extent with rest and a healthy diet, there is
People who have close contact with someone who
has hepatitis A:


should receive normal human immunoglobulin
within 2 weeks of exposure
Hepatitis A vaccine can be given at the same time
as the immunoglobulin.

16.  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 A Prevention - Immune Globulin

17.  There are currently four hepatitis A
vaccines and two combined hepatitis A /
hepatitis B vaccines registered for use
in Australia.

18. Vaccine …
 People at risk of getting both hepatitis A & B, (i.e.
healthcare workers, IV drug user, gay males (MSM)n
and travellers to developing countries ), should
consider receiving the combined hepatitis A /
hepatitis B vaccines.
 Recommendation : persons with hepatitis C be
vaccinated for hepatitis A, as well as for hepatitis B.

19.  Hepatitis A vaccines do not affect liver enzyme levels.
 Pregnant women should delay being immunized
against hepatitis A, unless there is a substantial risk
of them coming into contact with the virus.
 Local pain at the injection site may be experienced,
but this will only be for a short period of time

20.  Vaccination for hepatitis A should give
immunity against the disease for at
least 20 years.

21. 

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
H e p a t it is A V a c c in a t io n
S t r a t e g ie s
E p id e m io lo g i c
C o n s id e r a t io n s

22. Epidemiology
Hepatitis A virus is closely linked to social and
environmental situations, patterns of the virus are
recognized in:



areas where there is poor sanitation and hygiene
regions where there have been recent improvements
in the environment or economy
areas with high standards of hygiene and sanitation
but which are susceptible to new infections because
people may not have been previously exposed to
such viruses

24. Hepatitis A Prevention
To avoid transmission of hepatitis A,
always wash hands thoroughly:



after going to the toilet
before preparing food
after handling nappies and condoms

25. Hepatitis A Prevention
 Avoid sharing food, cutlery, crockery,
cigarettes and drinks with other
people.
 In a natural disaster, listen to warnings
about contaminated drinking water and
follow any instructions issued by the
relevant authorities.

27. H e p a titis B
V ir u s

28. Hepatitis B Virus - Virology






ds DNA
Complete Dane particle 42 nm ( the virus)
28 nm electron dense core ( include the HBcAg
and HBeAg
coat and the 22 nm free particles contain HBsAg
At least 4 phenotypes of HBsAg are recognized;
adw, adr, ayw and ayr.
The HBcAg is of a single serotype

29. Hepatitis B Virus - Virology
 It has not yet been possible to propagate
the virus in cell culture.

30.  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.
Hepatitis B Virus
Modes of Transmission

31. Transmission…



sharing toothbrushes or razors
unsterilised tattooing and body piercing
equipment
needle –stick injury

32.  Hepatitis B is found in body fluids
including blood, saliva, semen, mucus,
vaginal fluid and breast milk.

33. High Moderate
Low/Not
Detectable
blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
Concentration of Hepatitis B
Virus in Various Body Fluids

34.  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%
Hepatitis B - Clinical Features

35. 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

36. Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc anti-HBs
HBsAg
52 100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
0 4 8 12 16 20
W e e k s
24 28 32 36
a f t e r
Titre

37. IgM anti-HBc
HBsAg
Total anti-HBc
Acute
(6 months)
HBeAg
Chronic
(Years)
anti-HBe
0 4 8 Years
12 16 20 24 2832 36 52
Weeks after Exposure
Tit
r e
Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course

38. Chronic Infection
Chronic Infection (%)
Symptomatic
Infection
(%)
Birth
Symptomatic Infection
1-6 months 7-12 months
Age at Infection
1-4 years Older Children
and Adults
0
20
40
60
80
100
100
80
60
40
20
0
Outcome of Hepatitis B Virus Infection
by Age at Infection
Chronic
Infection
(%)

40. Diagnosis : Battery of serological Tests
MARKERS USED



 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.

41. Diagnosis…..



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.

42. Treatment


Interferon - for HBeAg +ve carriers with chronic active
hepatitis. Response rate is 30 to 40%.
 alpha-interferon 2b (original)
 alpha-interferon 2a (newer, claims to be more
efficacious and efficient)
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.

43. Treatment…..


Adefovir – less likely to develop resistance than
Lamivudine and may be used to treat Lamivudine
resistance HBV. However more expensive and
toxic
Entecavir – most powerful antiviral known,
similar to Adefovir
 Successful response to treatment will result in the
disappearance of HBsAg, HBV-DNA, and
seroconversion to HBeAg.

44. Prevention of Hepatitis B.. Ways to
reduce transmission
 wash hands after touching blood or body fluids



wear disposable gloves if giving someone first
aid or cleaning up blood or body fluids
avoid sharing toothbrushes, razors, needles,
syringes, personal hygiene items and grooming
aids or any object that may come into contact
with blood or body fluids
use new and sterile injecting equipment for each
injection

45. Prevention of Hepatitis B.. Ways to
reduce transmission…




cover all cuts and open sores with a bandage
wipe up any blood spills and then clean the
area with household bleach
throw away personal items such as tissues,
menstrual pads, tampons and bandages in a
sealed plastic bag
practice safe sex

46. 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.

47. Prevention….
 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.

49. Hepatitis C Virus
 Resembles flavivirus
 + stranded RNA genome of around 10,000 bases
 enveloped virus; morphological structure remains unknown
 HCV has been classified into a total of six genotypes
(type 1 to 6 on the basis of phylogenetic analysis
 Genotype 1 and 4 has a poorer prognosis and response
to interferon therapy,
 In Hong Kong, genotype 1 accounts for around 67%
of cases and genotype 6 around 25%.

50. Incubation period:
Clinical illness (jaundice):
Chronic hepatitis:
Persistent infection:
Immunity:
Average 6-7 wks
Range 2-26 wks
30-40% (20-30%)
70%
85-100%
No protective
antibody
response identified
H e p a t it is C - C l in ic a l
F e a t u r e s

51. 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, but with a lower frequency
i.e. chronic persistent hepatitis, chronic active
hepatitis, cirrhosis, and hepatocellular carcinoma.

52. S y m p t o
m s
a n ti-
H C V
A LT
N o rm
a l
H e p a t it is C V ir u s In f e c t io n
Typical Serologic Course
Titr
e
0 1 2 3 4 5 6 1 2 3 4
M o n Ye a r
s
t hTsim e a f t er
E x p o s u r e

53. R is k F a c t o rs
A s s o c ia t e d w it h
T r a n s m i s sio n o f
 Transfusion or tranHsplCantVfrominfected 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

55. Laboratory Diagnosis
 HCV antibody - 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 - by PCR, may be used to diagnose HCV
infection in the acute phase. 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.

56. 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.

57.  Screening of blood, organ, tissue donors
 High-risk behavior modification
 Blood and body fluid precautions
P r e v e n tio n o f
H e p a t it is C

59.  Hepatitis D, also called delta virus, is a
virus that is only found in people who
are already infected with hepatitis B.

60. RNA
H e p a t it is D
 antigen( D e lta H
)B
s
VA
g
ir u s

61. Hepatitis D Virus


The delta agent is a defective virus which
shows similarities with the viroids in plants.
It is a particle 35 nm in diameter


with delta antigen surrounded by an outer coat of
HBsAg.
The genome of the virus is very small and consists
of a single-stranded RNA

62.  Same way as hepatitis B


 through blood and infected blood products
through sexual intercourse
small risk of perinatal (maternal to infant)
transmission, but this is rare.

63. Those most at risk include people with
hepatitis B who:
 inject drugs
 practice unsafe sex
 have unsafe tattooing or body piercing

64.  Percutanous exposures
injecting drug use
 Permucosal exposures
sex contact
Hepatitis D Virus ,
Summary Modes of Transmission

65. The symptoms for hepatitis D are similar to
hepatitis B, such as:






 fatigue
abdominal pain
loss of appetite
nausea and vomiting
fever
joint aches
Jaundice

66. Hepatitis D - Clinical Features
 A person can be co-infected with
hepatitis D and hepatitis B at the same
time.
 severe acute disease.
 low risk of chronic infection

67. anti-HBs
IgM anti-HDV
HDV RNA
HBsAg
HBV - HDV Coinfection
Total anti-HDV
Time after Exposure
Typical Serologic Course
Symptoms
ALT
Elevated
Titre

68. – A person who is infected with hepatitis D
after becoming infected with hepatitis B is
said to have a super-infection.
 usually develop chronic HDV infection.
 high risk of severe chronic liver disease.
 may present as an acute hepatitis.
H e p a t it is D - C l in i c a l
F e a t u r e s

69. Jaundice
Symptoms
A LT
T o t a l a n t i-
H D V
Ig M a n ti-
H D V
H D V R N A
H B s A g
H B V - H D V
S uT
y
pp
i
ec
a
rlS
in
e
r
o
fleogcictC
io
ou
r
ns
e
T im e a f t er
E x p o s u r e
T itr e

70.  There is no specific treatment for
hepatitis D.
 There is some indication that antiviral
medication, such as interferon or
lamivudine, used to treat hepatitis B,
will also treat hepatitis D.

71.  Hepatitis D infection can be avoided by
being vaccinated against hepatitis B.
 A full course of hepatitis B vaccine for
children, adolescents and adults
consists of three doses with a specified
interval in-between each dose.

72. Vaccination…


Neonates should be given hepatitis B vaccination at
birth.
Babies born to hepatitis B carrier mothers should
also receive hepatitis B immunoglobulin to provide
immediate passive protection.
 Combination hepatitis A/hepatitis B vaccination is
recommended for those at risk of getting these
infections, and would offer protection against
hepatitis D.

73. 

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 D - Prevention

76.  Hepatitis E is a contagious viral
infection which causes acute
hepatitis but does not lead to
chronic hepatitis.
 Hepatitis E is found mostly in
developing countries, especially in
India, Asia, Africa and Central America.

77. Hepatitis E Virus




 Calicivirus-like viruses
unenveloped RNA virus, 32-34nm in
diameter
+ve stranded RNA genome, 7.6 kb in
size.
very labile and sensitive
Can be grown in cellculture

78. H e p a titis E
V ir u s

79.  By ingestion of contaminated water
 Easily transmitted by person to person
contact where household and personal
hygiene is poor

80. Transmission..
 Hepatitis E is most often spread
through fecal-oral route
 NO evidence of transmission through
needles, blood, body fluids or through
sexual contact

81.  Symptoms of hepatitis E are very similar to
those of hepatitis A:
fever
weakness
fatigue







loss of appetite
nausea
vomiting
The majority of people with hepatitis E
recover with no lasting immunity

82.  1-2% chance of developing sudden and
severe liver disease
 Hep E in pregnant women :with greater risk
of acute illness and liver failure, and
occasionally death.
 occurs mainly in developing countries
where hepatitis E is endemic, and where
there is limited ante-natal care and
maternal health is poor.

83.  Incubation period:
 Case-fatality rate:


Illness severity:
Chronic sequelae:
Average 40 days
Range 15-60 days
Overall, 1%-3%
Pregnant women,
15%-25%
Increased with age
None identified
Hepatitis E - Clinical Features

84. m s
A LT Ig G a n ti-
H E V
Ig M a n ti-
H E V
V ir u s in
s t o o l
0 1 2 3 4 5 6 7 8 9 1 1 1 1
0 1 2 3
Hepatitis E Virus Infection
T y p ic al
S e r o lo gSiy
cm
p t o
C o u r s e
i t er
W e e k s a f t er

85.  There is no medical treatment for
hepatitis E.
 The aim of treatment : to alleviate
symptoms through:


bed rest
fluid replacement

86.  There is no vaccination for hepatitis E.

87.  contaminated
Most outbreaks associated with faecally
drinking water.
 Large epidemics occurred in :Indian subcontinent, USSR,
China, Africa and Mexico.


USA and other nonendemic areas: 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.
H e p a t it is E -
E p id e m io lo g ic
F e a t u r e s

89.  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?
Prevention and Control Measures for
Travelers to HEV-Endemic Regions

91.  The hepatitis G virus is an RNA virus
(ribonucleic acid) similar to, but
distinct from, the hepatitis C virus.

92. •Hepatitis G virus: newly identified virus.
• Found among people who had blood transfusion --
developed post transfusion hepatitis which could not be
identified as any known virus.
•Infection with the hepatitis G virus can lead to persistent
infection in 15 - 30% of adults.
• Long term outcomes of the infection are not yet known.
• People with hepatitis A, B, or C can be co- or super-
infected with hepatitis G.
•There is no vaccination available for hepatitis G.

93. The transmission route known is through
infected blood products. This means that
those at risk of infection may include people
who:


 inject drugs
receive blood transfusions, haemodialysis,
tissue and organ transplants
have being unsafely tattooed and/or body
pierced.

94.  Can cause persistent viremia lasting for
several years.
 Means ‘presence of virus in the blood’ and
may not mean the person is sick.
 Like any viral infection, a person with
hepatitis G may experience some flu-like
symptoms.

95.  To date: no links established between
infection with hepatitis G virus and chronic
liver disease.
 People with hepatitis G who also have
hepatitis A, B or C do not appear to have
worse health outcomes because of the co-
infection.

96.  There is no treatment currently
available for hepatitis G.

97.  There is no vaccination for hepatitis G

98. Hepatitis TT

99. History and characteristics
 In 1997, a novel DNA virus was isolated from
the serum of a patient with post-transfusion
hepatitis of unknown etiology in Japan
 It was named TT virus (TTV) after the initials
of the index patient.
 TTV is a nonenveloped, single-stranded and
circular DNA virus, and its entire sequence of
~3.9 kb has been determined.

100. Transmission
 Recent reports indicate that TTV can be
transmitted via blood/blood products
 In another study, a high rate of cervical
carriage (66%) of TTV DNA was found
by PCR, which suggests that perinatal
and sexual transmission is possible.

101. Hepatitis F
 Hepatitis F is a hypothetical virus
linked to hepatitis.
 Several hepatitis F candidates emerged
in the 1990s; none of these reports
have been substantiated

102. End of lecture, thank you!