Hepatitis refers to inflammation of the liver caused by various factors, primarily viral infections such as hepatitis A, B, and C. The document explains the nature, transmission, clinical manifestations, prevention, and vaccination strategies for these viral hepatitis types, emphasizing the importance of sanitation and vaccination in reducing disease incidence. It highlights the difference between acute and chronic cases, the epidemiology of the infections, and the necessity of public health measures to control outbreaks.

1. VIRAL HEPATITIS
VIRAL HEPATITIS
A
A,B
,B,C
,C,
,D
D,
,E
E G
G ……..
……..
Dr.T.V.Rao MD
Dr.T.V.Rao MD

2. What Is Hepatitis?
What Is Hepatitis?
 The word "
The word "hepatitis
hepatitis" means inflammation of the
" means inflammation of the
liver
liver. Toxins, certain drugs, some diseases,
. Toxins, certain drugs, some diseases,
heavy alcohol use, bacterial and viral infections
heavy alcohol use, bacterial and viral infections
can all cause hepatitis. Hepatitis is also the
can all cause hepatitis. Hepatitis is also the
name of a family of viral infections that affect the
name of a family of viral infections that affect the
liver; the most common types in the United
liver; the most common types in the United
States are hepatitis A, hepatitis B, and hepatitis
States are hepatitis A, hepatitis B, and hepatitis
C.
C.

3. Hepatitis
Hepatitis
 Hepatitis
Hepatitis (plural
(plural hepatitides
hepatitides) implies
) implies
injury to the liver characterized by the
injury to the liver characterized by the
presence of inflammatory cells in the
presence of inflammatory cells in the
tissue of the organ. The name is from
tissue of the organ. The name is from
ancient Greek
ancient Greek hepar
hepar or
or hepato
hepato, meaning
, meaning
liver
liver, and suffix
, and suffix -itis
-itis, meaning
, meaning
"inflammation" (c. 1727)
"inflammation" (c. 1727)

4. Viral Hepatitis
Viral Hepatitis
 A group of
A group of viruses
viruses known as the hepatitis
known as the hepatitis
viruses cause most cases of liver damage
viruses cause most cases of liver damage
worldwide. Hepatitis can also be due to toxins
worldwide. Hepatitis can also be due to toxins
(notably alcohol), other infections.
(notably alcohol), other infections.
 Common viruses cause hepatitis include
Common viruses cause hepatitis include
A,B,C,D,E. G ……….
A,B,C,D,E. G ……….
 Acute hepatitis
Acute hepatitis
 Viral Hepatitis: Hepatitis A through E (more than
Viral Hepatitis: Hepatitis A through E (more than
95% of viral cause), Herpes simplex,
95% of viral cause), Herpes simplex,
Cytomegalovirus, Epstein-Barr, yellow fever
Cytomegalovirus, Epstein-Barr, yellow fever
virus, adenoviruses.
virus, adenoviruses.

5. A
A
“Infectious”
“Serum”
Viral
hepatitis
Enterically
transmitted
Parenteral
y
transmitte
d
F, G, TTV
? other
E
E
NANB
NANB
B
B D
D C
C
Viral Hepatitis - Historical Perspectives

6. 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
A B C D E

7. Hepatitis A
Hepatitis A
 Hepatitis A
Hepatitis A is an acute liver disease
is an acute liver disease
caused by the hepatitis A virus (HAV),
caused by the hepatitis A virus (HAV),
lasting from a few weeks to several
lasting from a few weeks to several
months. It does not lead to chronic
months. It does not lead to chronic
infection.
infection.

9. Hepatitis A Virus

10. Hepatitis A Virus
Hepatitis A Virus
 Naked RNA virus
Naked RNA virus
 Related to enteroviruses, formerly known as
Related to enteroviruses, formerly known as
enterovirus 72, now put in its own family: heptovirus
enterovirus 72, now put in its own family: heptovirus
 One stable serotype only
One stable serotype only
 Difficult to grow in cell culture: primary marmoset
Difficult to grow in cell culture: primary marmoset
cell culture and also in vivo in chimpanzees and
cell culture and also in vivo in chimpanzees and
marmosets
marmosets
 4 genotypes exist, but in practice most of them are
4 genotypes exist, but in practice most of them are
group 1
group 1

11. Nature of HAV virus
Nature of HAV virus
 HAV is a 27 – 30 nm
HAV is a 27 – 30 nm
spherical particle with
spherical particle with
cubic symmetry
cubic symmetry
 Contain linear single
Contain linear single
stranded RNA
stranded RNA
genome with size of
genome with size of
7.5 kb.
7.5 kb.
 Only one serotype
Only one serotype

12. HAV characters
HAV characters
 HAV are stable to treatment with 20% ether,acid
HAV are stable to treatment with 20% ether,acid
and heat at 60
and heat at 600
0
c for 1 hour.
c for 1 hour.
 The virus are destroyed by autoclaving at 121
The virus are destroyed by autoclaving at 1210
0
c
c
for 20 minutes, boiling in water for 5 minutes
for 20 minutes, boiling in water for 5 minutes
 Treatment with chlorine 1 ppm for 30 minutes
Treatment with chlorine 1 ppm for 30 minutes
 Heating food > 85
Heating food > 850
0
c for 1 minute destroys
c for 1 minute destroys

13. Culturing HAV virus
Culturing HAV virus
 Various primate cell lines will support
Various primate cell lines will support
grwoth of HAV,though fresh isolates of
grwoth of HAV,though fresh isolates of
virus are difficult to adapt and grow.
virus are difficult to adapt and grow.
 Usually to cytopathic effects are apparent
Usually to cytopathic effects are apparent

14. Pathology in Viral Hepatitis
Pathology in Viral Hepatitis
 Indicates inflamation of liver.
Indicates inflamation of liver.
 Microscopically there is spotty parenchymal cell
Microscopically there is spotty parenchymal cell
degeneration, with necrosis of Hepatocytes, with
degeneration, with necrosis of Hepatocytes, with
disruption of liver cell cords
disruption of liver cell cords
 The parenchymal changes are accompanied by
The parenchymal changes are accompanied by
Reticuloendothelial ( KUFFER) cell
Reticuloendothelial ( KUFFER) cell
hyperplasia,periportal infiltration by monoculear
hyperplasia,periportal infiltration by monoculear
cells and cell degeneration.
cells and cell degeneration.

15. Causes liver damage
Causes liver damage
 Localised areas of necrosis are frequently
Localised areas of necrosis are frequently
observed
observed
 Later accumulation of macrophages near
Later accumulation of macrophages near
degenerating Hepatocytes
degenerating Hepatocytes

16. Transmission Of Hepatitis A
Transmission Of Hepatitis A
:
: Ingestion of food or water contaminated
Ingestion of food or water contaminated
with faecal matter, Even in
with faecal matter, Even in
microscopic amounts, From close
microscopic amounts, From close
person-to-person
person-to-person

17.  Close personal contact
Close personal contact
(e.g., household contact, child day care
(e.g., household contact, child day care
centers)
centers)
 Contaminated food, water
Contaminated food, water
(
(e.g., infected food handlers, raw shellfish)
e.g., infected food handlers, raw shellfish)
 Blood exposure (rare)
Blood exposure (rare)
(e.g., injecting drug use, transfusion)
(e.g., injecting drug use, transfusion)
Not transmitted by Transplacental route
Not transmitted by Transplacental route
Hepatitis A Virus Transmission

18. Endemicity
Disease
Rate
Peak Age
of Infection Transmission Patterns
High 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 Person to person;
food and waterborne
outbreaks
Very low Very low Adults Travelers; outbreaks
uncommon
Global Patterns of
Hepatitis A Virus Transmission

19. Clinical Manifestations
Clinical Manifestations
 Incubation period 2 – 6 weeks
Incubation period 2 – 6 weeks
 May be asymptomatic
May be asymptomatic
 Overt illness in 5%
Overt illness in 5%
 Present as two stages,
Present as two stages,
1 Preicteric
1 Preicteric
2 Icteric
2 Icteric

20. Clinical features
Clinical features
 Malaise
Malaise
 Anorexia
Anorexia
 Nausea, omitting liver tenderness
Nausea, omitting liver tenderness
 Onset of Jaundice
Onset of Jaundice
 Recovery in 4-6 weeks
Recovery in 4-6 weeks
 Mortality 0.1 – 1 %
Mortality 0.1 – 1 %

21.  Complications: Fulminant hepatitis
Cholestatic
hepatitis
Relapsing
hepatitis
 Chronic sequelae: None
Hepatitis A - Clinical
Complications

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

23. Fecal
HAV
Symptoms
0 1 2 3 4 5 6 1
2
2
4
Hepatitis A Infection
Total anti-
HAV
Titer ALT
IgM anti-HAV
Months after exposure
Typical Serological Course

24. Treatment
Treatment
 No specific antiviral drug is available
No specific antiviral drug is available
 Treatment is symptomatic
Treatment is symptomatic
 Specific passive prophylaxis by pooled
Specific passive prophylaxis by pooled
normal human immunoglobulin given
normal human immunoglobulin given
before exposure or in early incubation
before exposure or in early incubation
period can prevent or attenuate clinical
period can prevent or attenuate clinical
illness.
illness.

25.  Many cases occur in community-wide outbreaks
Many cases occur in community-wide outbreaks
 no risk factor identified for most cases
no risk factor identified for most cases
 highest attack rates in 5-14 year olds
highest attack rates in 5-14 year olds
 children serve as reservoir of infection
children serve as reservoir of infection
 Persons at increased risk of infection
Persons at increased risk of infection
 travelers
travelers
 homosexual men
homosexual men
 injecting drug users
injecting drug users
Hepatitis A Vaccination Strategies
Epidemiologic Considerations

26. Vaccination for HAV
Vaccination for HAV
 Hepatitis A vaccination is recommended for all
Hepatitis A vaccination is recommended for all
children starting at age 1 year, travellers to
children starting at age 1 year, travellers to
certain countries, and others at risk.
certain countries, and others at risk.
 A safe and effective formalin inactivated alum
A safe and effective formalin inactivated alum
conjugated vaccine containing HAV grown in
conjugated vaccine containing HAV grown in
human diploid cell culture is available
human diploid cell culture is available
 A full course containing two intramuscular
A full course containing two intramuscular
injections of the vaccine
injections of the vaccine
 Protection starts after 4 weeks after injection and
Protection starts after 4 weeks after injection and
lasts for 10 – 20 years
lasts for 10 – 20 years

27.  Many cases occur in community-wide outbreaks
Many cases occur in community-wide outbreaks
 no risk factor identified for most cases
no risk factor identified for most cases
 highest attack rates in 5-14 year olds
highest attack rates in 5-14 year olds
 children serve as reservoir of infection
children serve as reservoir of infection
 Persons at increased risk of infection
Persons at increased risk of infection
 travelers
travelers
 homosexual men
homosexual men
 injecting drug users
injecting drug users
Hepatitis A Vaccination Strategies
Epidemiologic Considerations

28. Epidemiology
Epidemiology
 A major communicable disease in the
A major communicable disease in the
Devloping world
Devloping world.
.
 Well cooked food and sanitary water
Well cooked food and sanitary water
supply will protect the individual living
supply will protect the individual living
 Community hygiene is important in
Community hygiene is important in
schools, hostels and jails, as overcrowding
schools, hostels and jails, as overcrowding
and poor sanitation favour the spread
and poor sanitation favour the spread

29. Prevention of Hepatitis A
Prevention of Hepatitis A
Infection
Infection
 Pre-exposure
Pre-exposure
 travelers to intermediate and high
travelers to intermediate and high
HAV-endemic regions
HAV-endemic regions
 Post-exposure (within 14 days)
Post-exposure (within 14 days)
Routine
Routine
 household and other intimate contacts
household and other intimate contacts
Selected situations
Selected situations
 institutions (e.g., day care centers)
institutions (e.g., day care centers)
 common source exposure (e.g., food prepared by infected
common source exposure (e.g., food prepared by infected
food handler)
food handler)

30. Hepatitis B
Hepatitis B
Infection
Infection

31. Most Important Infectious
Most Important Infectious
Disease
Disease
 There are more than 350 million carriers
There are more than 350 million carriers
 25% of them will develop chronic active
25% of them will develop chronic active
hepatitis.
hepatitis.
 World wide 1 million deaths a years are
World wide 1 million deaths a years are
attributed to HBV related liver disease and
attributed to HBV related liver disease and
Hepatocellular Carcinoma
Hepatocellular Carcinoma

32. Hepatitis B
Hepatitis B
 Hepatitis B
Hepatitis B is a liver disease caused by the
is a liver disease caused by the
hepatitis B virus (HBV). It ranges in
hepatitis B virus (HBV). It ranges in
severity from a mild illness, lasting a few
severity from a mild illness, lasting a few
weeks (acute), to a serious long-term
weeks (acute), to a serious long-term
(chronic) illness that can lead to liver
(chronic) illness that can lead to liver
disease or liver cancer.
disease or liver cancer.

33. Hepatitis B Virus
 Blumberg in 1965
Blumberg in 1965
discovers, names as
discovers, names as
Australia antigen.
Australia antigen.
 1968 identified with
1968 identified with
association in serum
association in serum
hepatitis.
hepatitis.
 Surface component of
Surface component of
HBV called as surface
HBV called as surface
antigen.
antigen.

34. HBV Viruses Under Electron
HBV Viruses Under Electron
Microscope
Microscope
 Spherical particles 22 nm in
Spherical particles 22 nm in
diameter
diameter
 Filamentous or tubular 22 nm
Filamentous or tubular 22 nm
with varying length
with varying length
 Called as HBs Ag surface
Called as HBs Ag surface
components which are
components which are
produced in excess.
produced in excess.
 Third type double walled
Third type double walled
spherical structure 42 nm
spherical structure 42 nm
diameter called HBV
diameter called HBV
 Called as Dane
Called as Dane
particle
particle

35. HBV – Surface antigens
HBV – Surface antigens
 Enveloped proteins on
Enveloped proteins on
surface of virions and
surface of virions and
surplus 22 nm diameter
surplus 22 nm diameter
spherical and filamentous
spherical and filamentous
particles constitute the B
particles constitute the B
surface antigens
surface antigens
 HBs Ag consists two
HBs Ag consists two
major polypeptides and is
major polypeptides and is
glycolated
glycolated

37. Structure 0f Hepatitis B virus
Structure 0f Hepatitis B virus

38. HBV shows antigenic
HBV shows antigenic
diversity
diversity
 HBV shows antigenic diversity, two different
HBV shows antigenic diversity, two different
antigenic components and common group
antigenic components and common group
reactive antigen
reactive antigen a
a
 Two contain specific antigens
Two contain specific antigens
d y
d y
w r
w r
Only one member of each pair being present at a
Only one member of each pair being present at a
time
time
Divided into four Major antigenic subtypes
Divided into four Major antigenic subtypes
adw, adr, ayw, and ayr
adw, adr, ayw, and ayr

39. Geographic distribution
Geographic distribution
 ayw
ayw – common in Europe,Australia,and
– common in Europe,Australia,and
America.
America.
 adr - Prevalent in south, East India and Far
adr - Prevalent in south, East India and Far
east,
east,
 ayr
ayr - very rare
- very rare
 Core antigen HB c ag
Core antigen HB c ag
 Be HBe is a soluble non particle nucelocapsid
Be HBe is a soluble non particle nucelocapsid
protein
protein
 Both Hbc and Hbe are coded by same genes
Both Hbc and Hbe are coded by same genes

40. Replication
Replication
 The RNA dependent DNA synthesis takes
The RNA dependent DNA synthesis takes
place within the newly assembled Virion
place within the newly assembled Virion
core in the cytoplasam.
core in the cytoplasam.
 Hepadnaviruses the only virus that
Hepadnaviruses the only virus that
produce genome DNA by reverse
produce genome DNA by reverse
transcription with mRNA as the
transcription with mRNA as the
template
template

41. Pathogenesis of HBV infection
Pathogenesis of HBV infection
 Disease is Immune mediated
Disease is Immune mediated
 Hepatocytes carry viral antigen
Hepatocytes carry viral antigen
 Immune response subject to antibody dependent.
Immune response subject to antibody dependent.
 N K cell and cytotoxic T cell attack
N K cell and cytotoxic T cell attack
 In the absence of adequate immune response HBV
In the absence of adequate immune response HBV
infection may not cause hepatitis.
infection may not cause hepatitis.
 But lead to carrier state.
But lead to carrier state.
 Infection – Immunodeficient person are likely to because
Infection – Immunodeficient person are likely to because
asymptomatic carrier followed infection
asymptomatic carrier followed infection

42.  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%
Hepatitis B - Clinical Features

43. What are the clinical symptoms
What are the clinical symptoms
of Hepatitis B??
of Hepatitis B??

44. Spectrum of Chronic Hepatitis B
Spectrum of Chronic Hepatitis B
Diseases
Diseases
1
1Chronic Persistent Hepatitis -
Chronic Persistent Hepatitis -
asymptomatic
asymptomatic
2.
2. Chronic Active Hepatitis -
Chronic Active Hepatitis -
symptomatic exacerbations of hepatitis
symptomatic exacerbations of hepatitis
3. Cirrhosis of Liver
3. Cirrhosis of Liver
4. Hepatocellular Carcinoma
4. Hepatocellular Carcinoma

45. Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc anti-HBs
HBsAg
0 4 8 12 16 20 24 28 32 36 52 100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Weeks after Exposure
Titre

46. IgM anti-HBc
Total anti-HBc
HBsAg
Acute
(6 months)
HBeAg
Chronic
(Years)
anti-HBe
0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure
Titr
e
Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course

47.  High
High (>8%): 45% of global population
(>8%): 45% of global population
 lifetime risk of infection >60%
lifetime risk of infection >60%
 early childhood infections common
early childhood infections common
 Intermediate
Intermediate (2%-7%): 43% of global population
(2%-7%): 43% of global population
 lifetime risk of infection 20%-60%
lifetime risk of infection 20%-60%
 infections occur in all age groups
infections occur in all age groups
 Low
Low (<2%): 12% of global population
(<2%): 12% of global population
 lifetime risk of infection <20%
lifetime risk of infection <20%
 most infections occur in adult risk groups
most infections occur in adult risk groups
Global Patterns of
Chronic HBV Infection

49. 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

50. How Hepatitis B is transmitted
How Hepatitis B is transmitted
Contact with infectious blood, semen, and
Contact with infectious blood, semen, and
other body fluids from having sex with an
other body fluids from having sex with an
infected person, sharing contaminated
infected person, sharing contaminated
needles to inject drugs, or from an infected
needles to inject drugs, or from an infected
mother to her newborn.
mother to her newborn.

51.  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

52. Diagnosis
Diagnosis
 A battery of serological tests are used for the diagnosis of
A battery of serological tests are used for the diagnosis of
acute and chronic hepatitis B infection.
acute and chronic hepatitis B infection.
 HBsAg
HBsAg - used as a general marker of infection.
- used as a general marker of infection.
 HBsAb
HBsAb - used to document recovery and/or immunity to
- used to document recovery and/or immunity to
HBV infection.
HBV infection.
 anti-HBc IgM
anti-HBc IgM - marker of acute infection.
- marker of acute infection.
 anti-HBcIgG
anti-HBcIgG - past or chronic infection.
- past or chronic infection.
 HBeAg
HBeAg - indicates active replication of virus and therefore
- indicates active replication of virus and therefore
infectiveness.
infectiveness.
 Anti-Hbe
Anti-Hbe - virus no longer replicating. However, the
- virus no longer replicating. However, the
patient can still be positive for HBsAg which is made by
patient can still be positive for HBsAg which is made by
integrated HBV.
integrated HBV.
 HBV-DNA
HBV-DNA - indicates active replication of virus, more
- indicates active replication of virus, more
accurate than HBeAg especially in cases of escape mutants.
accurate than HBeAg especially in cases of escape mutants.
Used mainly for monitoring response to therapy.
Used mainly for monitoring response to therapy.

53. Treatment
Treatment
 Patients with Hepatitis needs supportive
Patients with Hepatitis needs supportive
treatment
treatment
 Recombinant Interferon alfa therpay is
Recombinant Interferon alfa therpay is
beneficial in HBV and HCV
beneficial in HBV and HCV

54. Treatment
Treatment
 Interferon -
Interferon - for HBeAg +ve carriers with chronic active hepatitis. Response
for HBeAg +ve carriers with chronic active hepatitis. Response
rate is 30 to 40%.
rate is 30 to 40%.
 alpha-interferon 2b (original)
alpha-interferon 2b (original)
 alpha-interferon 2a (newer, claims to be more efficacious and efficient)
alpha-interferon 2a (newer, claims to be more efficacious and efficient)
 Lamivudine
Lamivudine - a nucleoside analogue reverse transcriptase inhibitor. Well
- a nucleoside analogue reverse transcriptase inhibitor. Well
tolerated, most patients will respond favorably. However, tendency to
tolerated, most patients will respond favorably. However, tendency to
relapse on cessation of treatment. Another problem is the rapid emergence of
relapse on cessation of treatment. Another problem is the rapid emergence of
drug resistance.
drug resistance.
 Adefovir – less likely to develop resistance than Lamivudine and may be
Adefovir – less likely to develop resistance than Lamivudine and may be
used to treat Lamivudine resistance HBV. However more expensive and
used to treat Lamivudine resistance HBV. However more expensive and
toxic
toxic
 Entecavir – most powerful antiviral known, similar to Adefovir
Entecavir – most powerful antiviral known, similar to Adefovir
 Successful response to treatment will result in the disappearance of HBsAg,
Successful response to treatment will result in the disappearance of HBsAg,
HBV-DNA, and seroconversion to HBeAg.
HBV-DNA, and seroconversion to HBeAg.

55. High Risk Individuals
High Risk Individuals
 Medical and Dental surgeons
Medical and Dental surgeons
 Pathologists
Pathologists
 Physicians
Physicians
 Laboratory technicians
Laboratory technicians
 Blood bank personnel
Blood bank personnel

56. HBV is common in
HBV is common in
 Patients undergoing Dialysis
Patients undergoing Dialysis
 Staff of Hem dialysis Units
Staff of Hem dialysis Units

57. Vaccination Genetically
Vaccination Genetically
Engineered
Engineered
 Vaccination
Vaccination - highly effective
- highly effective
recombinant vaccines are now available.
recombinant vaccines are now available.
Vaccine can be given to those who are
Vaccine can be given to those who are
at increased risk of HBV infection such
at increased risk of HBV infection such
as health care workers. It is also given
as health care workers. It is also given
routinely to neonates as universal
routinely to neonates as universal
vaccination in many countries.
vaccination in many countries.

58. Hepatitis B Immunoglobulin
Hepatitis B Immunoglobulin
 Hepatitis B Immunoglobulin
Hepatitis B Immunoglobulin - HBIG may be
- HBIG may be
used to protect persons who are exposed to
used to protect persons who are exposed to
hepatitis B. It is particular efficacious within
hepatitis B. It is particular efficacious within
48 hours of the incident. It may also be given
48 hours of the incident. It may also be given
to neonates who are at increased risk of
to neonates who are at increased risk of
contracting hepatitis B i.e. whose mothers are
contracting hepatitis B i.e. whose mothers are
HBsAg and HBeAg positive
HBsAg and HBeAg positive

59. Blood screening is Mandatory
Blood screening is Mandatory
 Other measures
Other measures -
-
screening of blood
screening of blood
donors, blood and
donors, blood and
body fluid
body fluid
precautions is
precautions is
mandatory in
mandatory in
majority of
majority of
Countreis
Countreis

60. Universal Precautions
Universal Precautions
 Universal precautions," as defined by
Universal precautions," as defined by
CDC, are a set of precautions designed to
CDC, are a set of precautions designed to
prevent transmission of human
prevent transmission of human
immunodeficiency virus (HIV), hepatitis B
immunodeficiency virus (HIV), hepatitis B
virus (HBV), and other blood borne
virus (HBV), and other blood borne
pathogens when providing first aid or
pathogens when providing first aid or
health care.
health care.

61. Universal Precautions
Universal Precautions
 Under universal precautions, blood and
Under universal precautions, blood and
certain body fluids of all patients are
certain body fluids of all patients are
considered potentially infectious for HIV,
considered potentially infectious for HIV,
HBV and other blood borne pathogens.
HBV and other blood borne pathogens.

62. Hand washing Minimal health
Hand washing Minimal health
precaution to Medical and
precaution to Medical and
Paramedical staff
Paramedical staff

63. Hepatitis C Infection
Hepatitis C Infection
Hepatitis C Virus
Hepatitis C Virus
Non A, non B
Non A, non B
Hepaci virus
Hepaci virus

64. What is Hepatitis C Virus
What is Hepatitis C Virus
 Hepatitis C virus also known as Non A or
Hepatitis C virus also known as Non A or
Non B virus found while doing experiments
Non B virus found while doing experiments
on Chimpanzees.
on Chimpanzees.
 HCV infections are seen only in humans
HCV infections are seen only in humans
 The epidemiology is like HBV infection.
The epidemiology is like HBV infection.

65. HCV Virology
HCV Virology
 The virus is not been
The virus is not been
grown in culture
grown in culture
 The virus is 50- 60 nm with
The virus is 50- 60 nm with
linear single stranded RNA
linear single stranded RNA
genome surrounded by an
genome surrounded by an
enveloped carrying
enveloped carrying
glycoprotein spikes
glycoprotein spikes
 Now classified as
Now classified as
Hepacivirus in the family
Hepacivirus in the family
of Flaviviridae
of Flaviviridae
 Six genotypes are
Six genotypes are
identified, with high
identified, with high
mutability
mutability

66. hypervariable
region
capsid envelop
e
protein
protease/
helicase
RNA-
dependent
RNA polymerase
c22
5’
cor
e
E1 E2 NS
2
NS
3
33c
NS
4
c-100
NS
5
3’
Hepatitis C Virus

67. Hepatitis C Virus
Hepatitis C Virus
Genome resembled that of a flavivirus
Genome resembled that of a flavivirus
positive stranded RNA genome of around
positive stranded RNA genome of around
10,000 bases
10,000 bases
1 single reading frame, structural genes at the
1 single reading frame, structural genes at the
5' end, the non-structural genes at the 3' end.
5' end, the non-structural genes at the 3' end.
enveloped virus, virion thought to 30-60nm in
enveloped virus, virion thought to 30-60nm in
diameter
diameter
 Morphological structure remains unknown
Morphological structure remains unknown

68. Hepatitis C virus
Hepatitis C virus
Genotype 1 and 4 has a poorer
Genotype 1 and 4 has a poorer
prognosis and response to interferon
prognosis and response to interferon
therapy,
therapy,
In Hong Kong, genotype 1 accounts
In Hong Kong, genotype 1 accounts
for around 67% of cases and genotype
for around 67% of cases and genotype
6 around 25%.
6 around 25%.
Now 6 genotypes are identified
Now 6 genotypes are identified.
.

69. Terminology
Terminology
Term Definition % Nucleotide
Similarity
Genotype Genetic heterogeneity among
different HCV isolates
65.7-68.9
Subtype Closely related isolates within each
of the major genotypes
76.9-80.1
Quasispecies Complex of genetic variants within
individual isolates
90.8-99
Family Genus Species Genotype Subtype Quasispecies

70. Pathogenesis
Pathogenesis

71. 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 - Clinical
Features

72. How HCV transmitted
How HCV transmitted
 Blood transfusions
Blood transfusions
 Transplantation of organs
Transplantation of organs
 Injectable drug abusers
Injectable drug abusers
 Immunocompromised
Immunocompromised
 Sexual transmission ?
Sexual transmission ?
 Less important
Less important
 Vertical transmission is possible
Vertical transmission is possible

73. Clinical features
Clinical features
 Overt Jaundice is seen in 5% of patients
Overt Jaundice is seen in 5% of patients
 About 50 – 80% patients progress to
About 50 – 80% patients progress to
chronic hepatitis
chronic hepatitis
 May progress to Cirrhosis, or
May progress to Cirrhosis, or
Hepatocellular carcinoma
Hepatocellular carcinoma

74. Chronic Hepatitis C Infection
Chronic Hepatitis C Infection
 The spectrum of chronic hepatitis C infection is
The spectrum of chronic hepatitis C infection is
essentially the same as chronic hepatitis B
essentially the same as chronic hepatitis B
infection.
infection.
 All the manifestations of chronic hepatitis B
All the manifestations of chronic hepatitis B
infection may be seen, albeit with a lower
infection may be seen, albeit with a lower
frequency i.e. chronic persistent hepatitis, chronic
frequency i.e. chronic persistent hepatitis, chronic
active hepatitis, cirrhosis, and hepatocellular
active hepatitis, cirrhosis, and hepatocellular
carcinoma
carcinoma.
.

75. Transmission of HCV
Transmission of HCV
 Percutaneous
Percutaneous
 IV drugs
IV drugs
 Clotting factors before viral inactivation
Clotting factors before viral inactivation
 Transfusion, transplant from infected donor
Transfusion, transplant from infected donor
 Therapeutic (contaminated equipment, unsafe
Therapeutic (contaminated equipment, unsafe
injection practices)
injection practices)
 Occupational (needle stick)
Occupational (needle stick)
 Per mucosal
Per mucosal
 Perinatal
Perinatal
 Sexual
Sexual

76. HCV - Occupational
HCV - Occupational
Transmission
Transmission
 Inefficiently transmitted
Inefficiently transmitted
 Average incidence 1.8% following needle stick from
Average incidence 1.8% following needle stick from
HCV-positive source
HCV-positive source
 10 times lower than HBV infection
10 times lower than HBV infection
 Hollow-bore needles
Hollow-bore needles
 Case reports from blood splash to eye
Case reports from blood splash to eye
 No reports from skin exposures to blood
No reports from skin exposures to blood
 Prevalence 1-2% among health care workers
Prevalence 1-2% among health care workers
 Lower than in the general population
Lower than in the general population

77.  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
Risk Factors Associated
with Transmission of HCV

78. Symptoms
anti-
HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Hepatitis C Virus Infection
Typical Serologic Course
Titre
Mont
hs
Years
Time after
Exposure

80. Laboratory Diagnosis
Laboratory Diagnosis
 HCV antibody
HCV antibody - generally used to diagnose
- generally used to diagnose
hepatitis C infection. Not useful in the acute
hepatitis C infection. Not useful in the acute
phase as it takes at least 4 weeks after
phase as it takes at least 4 weeks after
infection before antibody appears.
infection before antibody appears.
 ELISA test results to be confirmed with
ELISA test results to be confirmed with
Immunoblotting assay
Immunoblotting assay

81. Molecular Methods in
Molecular Methods in
Diagnosis
Diagnosis
 HCV-RNA
HCV-RNA - various techniques are available e.g.
- various techniques are available e.g.
PCR and branched DNA. May be used to diagnose
PCR and branched DNA. May be used to diagnose
HCV infection in the acute phase. However, its main
HCV infection in the acute phase. However, its main
use is in monitoring the response to antiviral therapy.
use is in monitoring the response to antiviral therapy.
 HCV-antigen
HCV-antigen - an EIA for HCV antigen is available.
- an EIA for HCV antigen is available.
It is used in the same capacity as HCV-RNA tests but
It is used in the same capacity as HCV-RNA tests but
is much easier to carry out.
is much easier to carry out.

82. Prognostic Tests
Prognostic Tests
 Genotyping – genotype 1 and 4 have a worse prognosis overall and
Genotyping – genotype 1 and 4 have a worse prognosis overall and
respond poorly to interferon therapy. A number of commercial and
respond poorly to interferon therapy. A number of commercial and
in-house assays are available.
in-house assays are available.
 Genotypic methods – DNA sequencing, PCR-hybridization e.g. INNO-
Genotypic methods – DNA sequencing, PCR-hybridization e.g. INNO-
LIPA.
LIPA.
 Serotyping – particularly useful when the patient does not have
Serotyping – particularly useful when the patient does not have
detectable RNA.
detectable RNA.
 Viral Load – patients with high viral load are thought to have a
Viral Load – patients with high viral load are thought to have a
poorer prognosis. Viral load is also used for monitoring response to
poorer prognosis. Viral load is also used for monitoring response to
IFN therapy. A number of commercial and in-house tests are
IFN therapy. A number of commercial and in-house tests are
available.
available.

83. HCV Treatment
HCV Treatment
 α
α-
-Interferon
Interferon
 Ribavirin
Ribavirin
 Effective in about 50% of cases
Effective in about 50% of cases
 No vaccine
No vaccine

84. Treatment
Treatment
 Interferon
Interferon - may be considered for patients with
- may be considered for patients with
chronic active hepatitis. The response rate is
chronic active hepatitis. The response rate is
around 50% but 50% of responders will relapse
around 50% but 50% of responders will relapse
upon withdrawal of treatment.
upon withdrawal of treatment.
 Ribavirin
Ribavirin - there is less experience with ribavirin
- there is less experience with ribavirin
than interferon. However, recent studies suggest
than interferon. However, recent studies suggest
that a combination of interferon and ribavirin is
that a combination of interferon and ribavirin is
more effective than interferon alone.
more effective than interferon alone.

85.  Screening of blood, organ, tissue donors
 High-risk behavior modification
 Blood and body fluid precautions
Prevention of Hepatitis
C

86. Hepatitis D
Hepatitis D
Delta agent
Delta agent

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

89.  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 - Clinical
Features

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

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

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

93. Jaundice
Symptoms
ALT
Total anti-HDV
IgM anti-HDV
HDV RNA
HBsAg
HBV - HDV Superinfection
Typical Serologic Course
Time after
Titre

95.  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

96. Hepatitis E infection
Hepatitis E infection
NANB
NANB

97. Hepatitis E Virus
Hepatitis E Virus
 Calicivirus-like viruses
Calicivirus-like viruses
 unenveloped RNA virus, 32-34 nm in
unenveloped RNA virus, 32-34 nm in
diameter
diameter
 +ve stranded RNA genome, 7.6 kb in size.
+ve stranded RNA genome, 7.6 kb in size.
 very labile and sensitive
very labile and sensitive
 Can only be cultured recently
Can only be cultured recently

98. Hepatitis E Virus

99.  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 - Clinical Features

100. Symptoms
ALT IgG anti-HEV
IgM anti-HEV
Virus in stool
0 1 2 3 4 5 6 7 8 9 1
0
1
1
1
2
1
3
Hepatitis E Virus Infection
Typical Serologic
Course
Titer
Weeks after

101.  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.
Hepatitis E -
Epidemiologic Features

103.  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

104. Hepatitis G virus
Hepatitis G virus
 A new virus recently identified in Humans.
A new virus recently identified in Humans.
 Not grown in culture lines
Not grown in culture lines
 RNA genome is cloned
RNA genome is cloned
 Its role still for debate
Its role still for debate
 HGV RNA was found in acute, chronic, fulminant
HGV RNA was found in acute, chronic, fulminant
hepatitis , hemophiliacs, patients with multiple
hepatitis , hemophiliacs, patients with multiple
transfusions
transfusions
 It resembles HCV In all other aspects
It resembles HCV In all other aspects

105. Protect yourself
Protect yourself
Medical and Paramedical staff can
Medical and Paramedical staff can
reduce, avoid the incidences of
reduce, avoid the incidences of
accidental infection with
accidental infection with
HBV,HCV,HDV,and Hepatitis G
HBV,HCV,HDV,and Hepatitis G
infections with, safe handling of
infections with, safe handling of
needles
needles

106. Prevent needle stick injuries
Prevent needle stick injuries

107. Report your needle stick injuries
Report your needle stick injuries
to higher authorities
to higher authorities

108. Created for benefit of
Created for benefit of
Medical and Paramedical
Medical and Paramedical
Students in Developing
Students in Developing
World
World
Dr.T.V.Rao MD
Dr.T.V.Rao MD
Email
Email
doctortvrao@gmail.com
doctortvrao@gmail.com