1. Dr Hassan K.S
MBBS, Ilorin
21 August, 2013

2. outlines
 Introduction/background
 Epidemiology/burden
 Virology/ pathophysiology
 Mode of transmission
 Management of exposed infants
 Post exposure prophylaxis and follow up
 HBV antigenic markers

3. Introduction
 Hepatitis B virus(HBV) is a hepatotropic
virus discovered in 1966
 Has infected more than 2billions people
worldwide
 An established cause of chronic hepatitis
 Human carcinogen cause of upto 80% of
hepatocellular carcinoma;2nd only to
tobacco
 HBV causes acute and chronic liver
diseases

4. Introduction
 Clinical presentation ranges from
subclinical to symptomatic hepatitis; in rare
instances fulminant hepatitis
 Long term complication include cirrhosis
and HCC
 In addition to human sufferings the social
and economics implications of these
diseases are huge
 More than $1billion dollars are spent yearly
for hep B related hospitalization

5. Epidemiology/global burden
International statistics
 HBV infects more than 350 million people worldwide.
 Approximately 5% of the world's population has
chronic HBV infection
 It is the leading cause of chronic hepatitis, cirrhosis,
and hepatocellular carcinoma worldwide.
 Each year, an estimated 500,000 people die of
cirrhosis and hepatocellular carcinoma caused by
chronic infection
 And an additional 40,000 people die of acute
hepatitis B.
 An estimated 500,000-1,000,000 persons die
annually from HBV-related liver disease.

6. Hepatitis B In the World
 10-30 million will become infected each
year.
 Approximately 2 people die each minute
from hepatitis B.
 25-40% of chronic hepatitis patient die
from liver cirrhosis and HCC

7. Symptomatic Infection
Chronic Infection
Age at Infection
Chronic Infection (%)
SymptomaticInfection(%)
Birth 1-6 months 7-12 months 1-4 years Older Children
and Adults
0
20
40
60
80
100100
80
60
40
20
0
Outcome of Hepatitis B Virus Infection
by Age at Infection
ChronicInfection(%)

8. 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

10. Hepatitis B In the United
States
 12 million Americans have been infected (1
out of 20 people).
 More than one million people are
chronically infected .
 Up to 100,000 new people will become
infected each year.
 5,000 people will die each year from
hepatitis B and its complications.
 Approximately 1 health care worker dies
each day from hepatitis B.

11.  An estimated 25,000 infants are born to
hepatitis B surface antigen (HBsAg)-
positive women annually in the United
States. With no intervention, 40%–90%
of these infants will acquire hepatitis B
virus (HBV) infection
 Approximately 90% of infected infants
develop chronic HBV infection, with a
15%–25% risk for premature death from
cirrhosis or cancer of the liver

12. Hepatitis B Disease Progression
Acute
Infection
Chronic
Infection Cirrhosis
Death
5%-10% of
chronic HBV-
infected
individuals1
Liver
Failure
(Decompensation
)
>30% of
CHB
individuals1
• >90% of infected
children progress to
chronic disease
• <5% of infected
immunocompetent
adults progress to
chronic disease1
24% of patients
decompensate within
5 years of developing
cirrhosis 2
Liver
Cancer
(HCC)
Liver
Transplantation
• Torresi J, Locarnini. Gastroenterology 2000.
• Fattovich G et al. Hepatology 1995

13. Virology
 It is a circular partially dsDNA virus
 Hepadnaviridae family (DNA)
 Numerous antigenic components
 HBsAg,HBeAg, HBcAg
 Humans are only known host
 Resilient virus
 Infectious on surfaces for >7days at room
temp

14. HBV : Structure
 Virion also referred to as Dane particle (ds-stranded
DNA)
 42nm enveloped virus
 Core antigens located in the center (nucleocapsid)
* Core antigen (HBcAg)
* e antigen (HBeAg)- an indicator of transmissibility
(minor component of the core- antigenically distinct from
HBcAg)
 22nm spheres and filaments other forms- no DNA in
these forms so they are not infectious (composed of
surface antigen)- these forms outnumber the actual
virions

15. HBV : Structure

16. Transmission
 Perinatal exposure
 Percutaneous exposure
 Sexual exposure

17. Transmission
 The virus is transmitted via parenteral or mucosal
exposure to HBV infected fluid
 Perinatal transmission from mother at birth is very
efficient
 The precise mechanism of HBV transmission
remains unclear,
 It appears that infection occur predominantly
intrapartum or, rarely, in utero(transpacental).
 Hepatitis B viral DNA and HBsAg have been
detected in amniotic fluid, placental cells, and vaginal
secretions of HBsAg-positive women during
pregnancy and in cord blood of their neonates
 Transmission of HBV through breast milk is not a
significant source of infection

18.  The overall rate of transmission of HBV
from an infected HBsAg-positive mother to
her neonate during the perinatal period
ranges from 5-90%
 This risk depends on whether the mother
also has a positive hepatitis B e antigen
(HBeAg) test or/and high viral load
 The mode of delivery (vaginal versus
caesarean) does not appear to have an
impact on the risk for perinatal HBV
infection

19. Hepatitis B Perinatal
Transmission
 If mother positive for HBsAg and
HBeAg
 70%-90% of infants infected
 90% of infected infants become
chronic carriers
 If positive for HBsAg only
 20% of infants infected
 90% of infected infants become
chronic carriers

20. 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

21. Management of exposed
infants
 Mother is HBsAg Positive
 Give 0.5 mL of HBIG and 0.5 mL of single-
antigen hepatitis B vaccine within 12 hours of
birth. Both HBIG and vaccine should be given
intramuscularly at different sites.
 Give subsequent doses of hepatitis B vaccine
according to the immunization schedule for a
child born to a mother who is HBsAg positive.
 All children born to women who are HBsAg
positive should receive follow-up to ensure the
child has completed the vaccine series and that
immunoprophylaxis was successful.

22.  Test for HBsAg and hepatitis B surface antibody
(anti-HBs) 1-2 months after completing at least three
dose in the HBV vaccine series (e.g. at 9-18 months
of age, generally at the next well-child visit).
○ Screening should not be performed before 9 months of
age, or earlier than 4 weeks following the last vaccine
dose.
○ Children with anti-HBs levels 10 mIU/mL or greater
have responded appropriately to the vaccine series and
thus do not need additional follow-up.
○ Children with anti-HBs levels less than 10 mIU/mL
should be revaccinated with a second three-dose
hepatitis B series and retested for anti-HBs 1-2 months
after completing the vaccine series.
○ HBsAg positive children will need life-long follow-up for
their HBV infection.

23.  Low birth weight infants (less than 2000 grams)
should receive a single-antigen birth dose but
this dose should not be counted towards the
three dose series. The full three dose series
should be started at 1-2 months of age; thus,
these children should receive a total of four
vaccine doses due to the theoretical risk of a
poor immune response to immunization.
○ Test for HBsAg and hepatitis B surface antibody
(anti-HBs) 1-2 months after completing the fourth
dose in the HBV vaccine series and then manage
as in 1.d.i-iii.

24. Mother Has Unknown HBsAg
Status at Time of Birth
 Begin the single-antigen hepatitis B vaccine
series within 12 hours of birth while the
mother's HBsAg test is pending.
 If the mother's HBsAg test result is positive,
the child should receive 0.5 mL of HBIG
intramuscularly as soon as possible (within
72hrs of birth) and the vaccine series and
screening should be completed.
 If the mother's HBsAg test result is negative,
the child should receive the routine series of
preventive hepatitis B vaccine.

25.  Low birth weight infants (less than 2,000 grams)
should receive both single-antigen hepatitis B
vaccine and HBIG (0.5 mL) if the mother's HBsAg
status cannot be determined within 12 hours of birth.
 The birth dose of vaccine should not be counted
towards the three dose series.
 The full three dose series should be started at 1
months of age; thus, these children should receive a
total of four vaccine doses due to the theoretical risk
of a poor immune response to immunization.
○ Test for HBsAg and hepatitis B surface antibody (anti-
HBs) 1-2 months after completing the fourth dose in the
HBV vaccine series and then manage accordingly

26. Mother is HBsAg Negative
 Give 0.5 mL of single-antigen hepatitis B
vaccine intramuscularly before the infant is
discharged from the hospital and complete
the series accordingly .
 If a child is not immunized before discharge,
single-antigen vaccine should be given
within a month of birth and the series should
be completed accordingly.
 Medically stable, low birth weight infants
(less than 2,000 grams) should receive
their first dose 1 month after birth.

27.  The child should complete the remaining
three doses of vaccine per the
immunization schedule for full term
infants, making sure the 2nd dose is
given at least 1month after the first dose

28.  Impact of perinatal HBV transmission
○ Unlike adults who have a high rate of
spontaneous clearance of HBV following
acute infection, approximately 90% of children
infected during the perinatal period develop
chronic infection, and up to 25% will develop
chronic active hepatitis as adults.
 Susceptible children not infected in the
perinatal period are at risk for infection
from horizontal transmission of HBV in
the first five years of life

29.  In those mothers with HBeAg, the risk of
HBV perinatal transmission is reduced
from 70-90% to approximately 5-15%
when the infant receives postnatal
immunoprophylaxis with both hepatitis B
immune globulin (HBIG) and hepatitis B
vaccine series
 the risk is reduced to approximately 20%
with regimens that use multiple doses of
HBIG only or the vaccine series alone

30. Hep B serological markers

31. Prevention of perinatal
transmission of HBV
 Universal prenatal HBsAg screening
 Further evaluation of HBsAg +ve
pregnant women
 Antiviral therapy/immunotherapy before
delivery to lower viral load
 Infant immunoprophylaxis