Hepatitis viruses can cause liver infection. There are six main types: A, B, C, D, E, and G. Type B virus (HBV) is unique as it is a DNA virus while the others are RNA. HBV can cause both acute and chronic infection. It is transmitted through blood and bodily fluids. While types A, E, and some cases of B can be prevented through vaccination, there is currently no vaccine for types C and D. HBV infection requires monitoring of antigen and antibody blood markers to determine infection status and risk of progression to chronic liver disease or cancer.

1. Hepatitis Viruses
II MBBS
Dr. Sudheer Kher
Microbiology

2. Introduction
• Primary infection of liver
• Divided into six types:A, B, C, D, E, G
• Type F : transfusion associated hepatitis
a mutant (HBx) of HBV.
• All are RNA virus except HBV which is a
DNA virus.

3. A
“Infectious”
“Serum”
Viral
hepatitis
Enterically
transmitted
Parenterally
transmitted
others – F, G
E
“NANB”
B D
C
Viral Hepatitis – Clinical Classification

4. Viral Hepatitis Overview
Types of Viral Hepatitis
A B C D E
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
infectio
n
no yes yes yes no
Prevention pre-
exposure
pre/post
-
exposure
blood donor
screening;
pre/post
-
exposure
ensure safe
drinking
immunization immunization risk behavior immunization; water
modification risk behavior
modification

5. A, B, Cs of Viral Hepatitis
• A
– fecal-oral spread: hygiene, drug use, men having sex
with men, travelers, day care, food
– vaccine-preventable
• B
– sexually transmitted – 100x more infectious than HIV
– blood-borne (sex, injection drug use, mother-child, and
health care)
– vaccine-preventable
• C
– blood borne (injection drug use primarily)
– 4-5 times more common than HIV
– NOT vaccine-preventable!

6. Acute Hepatitis – Clinical Symptoms
Asymptomatic > Symptomatic > Fulminant Liver
Failure > Death
Symptoms (if present) are the same, regardless of
cause (e.g., A, B, C, other viruses, toxins)
Pre- icteric stage
– Nausea, vomiting
– Abdominal pain
– Loss of appetite
– Fever
– Diarrhea
Icteric stage
– Light (clay) colored stools
– Dark urine
– Jaundice (yellowing of eyes, skin)

7. Hepatitis B Virus (HBV)
Historical Aspect
• 1965
• Blumberg
• Australia antigen

8. Structure of HBV
• Hepadnaviridae family
• 42 nm DNA virus with an outer envelope
and inner core
Envelope (HBsAg)
Nucleocapsid / Core
(HBcAg, HBeAg)
DNA polymerase
Circular DNA : partly
double stranded

9. Structure of HBV
• Exists in 3 different forms in
serum of infected
individuals:
1. Spherical particle – 22nm, most
abundant
2. Tubular or filamentous particle –
22nm
3. Dane particle – 42nm, few in no,
double walled spherical
structure, true infectious form of
HBV.
Spherical & tubular particles
constitute the surface Ag of HBV.

10. Hepatitis B Antigens
• Hepatitis B surface antigen(S): HBs Ag – the
envelope protein – detectable in blood
• Hepatitis B core antigen (HBcAg) – not
detectable in blood.
• Hepatitis B e antigen (HBeAg) - Detectable in
blood during active viral multiplication,
generally at the same time as HBsAg

11. HBsAg Antigenic Diversity
• Two different antigenic components
 Group reactive Ag : “a” , common to all
 Type specific Ags : two pairs “d -y, w –r” ; only one member of each pair
present at a time
• Four major antigenic subtypes of HBsAg – adw, adr, ayw, ayr
• Distinct geographical distribution :
 ayw – West asia
 adw – Europe, Australia & the Americas
 adr – south & east India, far East
 ayr – very rare
• Role in outbreaks – index case & contacts have same subtype

12. • Incubation period: long Average 60- 90 days
Range 45-180 days
• Fever is not prominent
• 90- 95% with acute hepatitis recover within 1-2
months of onset.
• Mortality in about 0.5-2 % of cases.
• 1-10% develop chronic infection.
Hepatitis B – Clinical Features

13. Outcome of HBV Infection
Infection
Asymptomatic
Symptomatic
acute hepatitis B
Resolved
Immune
Chronic infection
Asymptomatic
Cirrhosis
Liver cancer
Resolved
Immune
Chronic
infection
Asymptomatic
Cirrhosis
Liver cancer

14. Epidemiology
• Natural infection occurs only in humans.
• Virus maintained in carriers.
• Largest carrier pool in China followed by
India.
• Carrier – a person with detectable HBsAg in
blood for more than 6 months.
• Carrier state is more common in males.
• Carriers - two types:
1.Super carriers – high titre HBsAg, along with HBeAg,
DNA polymerase and HBV in circulation, with elevated
transaminases.
2.Simple carriers – low infectivity & low titres of HBsAg.

15. Epidemiology
• Prevalence of hepatitis carriers - varies in
different countries
1.High endemicity: carrier rate >8% as in SE Asia,
China, parts of S. America
2.Intermediate: 2 to 7 % as in ME Asia, India, S. Asia
3.Low endemicity: <2% as in Western Europe,
N. America, Australia

16. • Sexual
• Parenteral
• Perinatal
HBV Modes of Transmission

17. High Moderate
Low/Not
Detectable
blood
serum
wound exudates
semen
vaginal fluid
saliva
urine
feces
sweat
tears
breast milk
Concentration of HBV
in Various Body Fluids

18. • IV drug abuse – HBV transmission is
Four times more common than HIV
• Transfusion or transplant from
infected donor
• Occupational exposure to
blood - Mostly needle sticks
• Iatrogenic – dialysis, unsafe
injection practices (reuse of
needles/syringes, contaminated multiple
dose medication vials), dental
procedures, blood bank
Risk Factors Associated with
Transmission of HBV

19. • Transmission from Carrier mothers
– by contact of maternal blood with the skin
& mucosa of the fetus during birth
– Very high (60-90%) if the mother is
HBeAg +ve and low (5-15%) if negative
• High risk Sexual behaviour -
Multiple sex partners, homosexuals &
those diagnosed with STDs like HIV,
gonorrhea etc
Risk Factors Associated with
Transmission of HBV

20. Household Transmission of HBV
• Rare but not absent
• Could occur through
percutaneous / mucosal
exposures to blood
– Theoretically through sharing of
contaminated personal articles
(razors, toothbrushes)
– Contaminated equipment used
for home therapies
► IV therapy
► Injections

21. Laboratory Diagnosis
• Serology – specific diagnosis, demonstration of
serological markers
• HBV DNA levels – indicator of viral replication &
great infectivity
- measured by PCR, DNA:DNA hybridization.
• Histopathology – ground
glass appearance of
infected hepatocytes due
to HBsAg.

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

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

24. Interpretation of serological markers
Virus/ Antibody markers
Interpretation
HBsAg HBeAg Anti
-
HBc
Anti-
HBs
Anti-
HBe
+ + Ig M - - Acute infection, highly
infectious
+ + Ig G - - Late/chronic or carrier
state, highly infectious
+ - Ig G - +/ - Late/chronic or carrier
state, low infectivity
- +/ - Ig M - +/ - Infectious,rarely seen,
window phase
- - Ig G +/ - +/ - Remote infection, nil or
very low infectivity
- - - + - Following vaccination

25. Reduce or Eliminate Risks for
Acquiring HBV Infection
• Screening and testing donors of blood, organs,
and tissues
• Virus inactivation of plasma-derived products
• Risk-reduction counselling and services
– Obtain history of high-risk drug and sex behaviors
– Provide information on minimizing risky behavior,
including referral to other services
– Vaccinate against hepatitis A and/or hepatitis B
• Infection control practices
• Blood and body fluid precautions

26. Passive Immunisation - HBIG
• Hyperimmune hepatitis B immune globulin
(HBIG) given soon after exposure to infection
– 300-500 IU I.M., single dose
– Prepared from human volunteers with high titres of anti-
HBs
– Also given to protect patient from severe recurrent HBV
infection following liver transplantation
– Protects against illness & carrier state, may not prevent
infection.

27. Active Immunisation – Hep. B vaccine
• 1st vaccine licensed for use in 1982
• Prepared from pooled plasma of healthy
human carriers with high level antigenemia
• 22nm HBs Ag particles were used
• Disadvantages:
– limited availability
- not totally free from possible risk of unknown
pathogens.

28. Recombinant Vaccine
• Currently used
• Genetically engineered by cloning the
S gene of HBV in baker’s yeast
• Given with alum adjuvant
• Route & Site - IM into deltoid or, in infants
into the anterolateral aspect of thigh
• Three doses: 0, 1 & 6 months
• Booster only for those who are at high risk
• Seroconversion occurs in 90% of vaccinees.

29. New Vaccine
• Special vaccine containing all antigenic
components (S, Pre S1 & Pre S2) of HBsAg.
• Gives greater seroconversion.

30. Post Exposure Prophylaxis (PEP)
• For non immune persons exposed to HBV:
1.Percutaneous or mucosal exposure to HBsAg +ve
blood
2.Sexual exposure to HBsAg +ve person
3.Perinatal exposure of an infant to HBsAg +ve
mother.
• PEP includes HBIG +full course of Hep B
vaccine.

31. 6 months old
Hepatitis B
Vaccine
Baby Shots for Hepatitis B
if the mother has Hepatitis B
1 - 2 months old
Hepatitis B
Vaccine
+
Birth
H-BIG
Hepatitis B
Vaccine

32. If you have never had hepatitis B,
you can get 3 shots . . .
. . . and get long lasting protection.
3
2
1
Hepatitis B can be prevented!

33. Treatment
• Supportive care
• Therapy
1.IFN alpha 2b – mimics cells natural defense
mechanisms
2.Adevofir Dipivoxil – inhibits HBV DNA polymerase,
chronic hepatitis
3.Lamivudine – inhibits reverse transcriptase

34. HBsAg
RNA
d antigen
Hepatitis D (Delta) Virus

35. Structure & Properties
• Identified in 1977.
• Spherical, 36 nm
• Outer coat made up of HBsAg
• Defective RNA virus which depends on HBV
for its replication and expression
• Can survive & replicate only as long as HBV
infection persists in the host.

36. Two types of infection occurs:
• Coinfection with HBV
– HBV & HDV are transmitted together
– severe acute disease
– low risk of chronic infection
• Superinfection on top of chronic HBV
– usually develop chronic HDV infection
– high risk of severe chronic liver disease
Hepatitis D - Clinical Features

37. Laboratory Diagnosis
• Detection of viral Ag in liver cell nuclei – IF
• Detection of Abs: ELISA
1. Ig M Ab: appears 2-3 weeks after infection
2. Then appears Ig G
3. Persistence of Ig G Abs for years – chronic
infection
• RNA sequencing
• PCR

38. • Percutanous exposures
injecting drug use
• Permucosal exposures
sexual contact
Hepatitis D Virus
Modes of Transmission

39. • HBV-HDV Coinfection
– Pre or postexposure prophylaxis to prevent HBV
infection (HBIG and/or Hepatitis B vaccine)
• HBV-HDV Superinfection
– Education to reduce risk behaviors among persons
with chronic HBV infection
Hepatitis D - Prevention

40. 29/05/07 Dr Ekta Chourasia, Microbiology