Management of hbv exposed infants

MANAGEMENT OF NEWBORN

EXPOSED TO PERINATAL HBV

Dr Hassan K.S

MBBS, Ilorin

21 August, 2013

outlines

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

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

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

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.

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

Symptomatic Infection

Chronic Infection

Age at Infection

Chronic Infection (%)

Sym

ptom

atic Infection

(%)

Birth 1-6 months 7-12 months 1-4 years Older Childrenand Adults

0

20

40

60

80

100100

80

60

40

20

0

Outcome of Hepatitis B Virus Infectionby Age at Infection

Ch

ron

ic I

nfe

ctio

n (

%)

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 populationlifetime risk of infection 20%-60%infections occur in all age groups

Low (<2%): 12% of global populationlifetime risk of infection <20%most infections occur in adult risk groups

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.

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

Hepatitis B Disease Progression

Acute Infection

Chronic Infection

Cirrhosis

Death

5%-10% of chronic HBV-infected individuals1

Liver Failure

(Decompensatio

n)

>30% of CHB

individuals1• >90% of infected

children progress to chronic disease

• <5% of infected immunocompetent adults progress to chronic

disease124% of patients decompensate within 5 years of developing cirrhosis 2

Liver Cancer (HCC)

Liver Transplantatio

n

• Torresi J, Locarnini. Gastroenterology 2000. • Fattovich G et al. Hepatology 1995

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

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

HBV : Structure

Transmission

Perinatal exposure Percutaneous exposure Sexual exposure

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

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

Hepatitis B Perinatal Transmission If mother positive for HBsAg and HBeAg

70%-90% of infants infected90% of infected infants become chronic

carriers If positive for HBsAg only

20% of infants infected90% of infected infants become chronic

carriers

High ModerateLow/Not

Detectable

blood semen urineserum vaginal fluid feces

wound exudates saliva sweat

tearsbreastmilk

Concentration of Hepatitis B Virus

in Various Body Fluids

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.

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.

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.

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.

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

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.

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

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

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

Hep B serological markers

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

Thanks for your attention