Hepatitis B in Pregnancy

Hepatitis B in Pregnancy
Aboubakr elnashar
Benha university Hospital, Egypt
Aboubakr ElnasharAboubakr Elnashar

Contents
Epidemiology
Natural history
Lab markers
Impact on pregnancy
Impact of pregnancy
Transmission
How to minimize the risk of transmission ?
Mode of delivery and Breastfeeding
HBV-Infected Women Who Desire Pregnancy
Algorithm
Take home message

Epidemiology
 Of the 400 million individuals with chronic HBV
worldwide: 50% acquired their infections
perinatally.
 90% of infected infants will become chronic
carriers of hepatitis B
2nd carcinogens after tobacco (WHO)
Gish RG and AC Gadano. J Vir Hep. 2006.Aboubakr ElnasharAboubakr Elnashar

Sequelae:
Chronic hepatitis
Cirrhosis
Carcinoma: Hepatocellular.
Mortality: 25% in perinatally acquired disease
7% in adult acquired disease
2 million/Y
9th leading cause worldwide
Liver International 2009; 29 : 135

Etiology
Double-stranded DNA virus in the core particle.
a hepa DNA virus whose DNA codes for four
viral products.
Incubation period
Long (up to 180 days).

Clinical picture
Most infections during pregnancy: chronic,Most infections during pregnancy: chronic,
asymptomaticasymptomatic
Acute infection:±asymptomatic and anicteric.
50%: asymptomatic.
Physical Exam
Urticarial rash
Arthralgias and arthritis
Myalgias
Hepatomegaly and/or right upper quadrant
tenderness
Jaundice is less common.

Clinical course
After acute hepatitis
90%: recover completely.
10%: chronic hepatitis B: ¼ chronic liver disease
HBeAg positive: at greatest risk for hepatocellular
carcinoma
(Yang and co-workers, 2002).

Hepatitis B Lab Markers
 HBsAgHBsAg:: Marker of current infectionMarker of current infection
 HBeAgHBeAg:: marker of active replication,marker of active replication,
Identification of persons at increasedIdentification of persons at increased
risk for transmitting HBVrisk for transmitting HBV
 HBV DNA:HBV DNA: Viral loadViral load

 Anti-HBs: marker of resolved infection
/immunity after immunization
 AntiAnti--HbeHbe:: Identification of person with lower riskIdentification of person with lower risk
for transmitting HBVfor transmitting HBV

Impact of HBV on Pregnancy
 Yes
Gestational diabetes
lower Apgar scores1,2
PPreterm deliveryreterm delivery
 No association with adverse pregnancy
outcomes3-5
1. Lao J Hepatol 2007 2. Tse J Hepatol 2005 3. Pastorek AJOG 1988
4. Wong Am J Perinatol 1999 5. To Aust N Z J Obstet Gynaecol 2003

Impact of Pregnancy
 Liver disease:Liver disease:
–– No worsening of liver disease in majority ofNo worsening of liver disease in majority of
womenwomen
(Terrault NA, et al, 2007)
---- Case reports of hepaticCase reports of hepatic
exacerbations/fulminant hepatic failuresexacerbations/fulminant hepatic failures
((MahtabMahtab MA, etMA, et al,al, 20082008))

Transmission
By any body fluid, but exposure to virus-laden serum is the most
efficient mode of transmission.
1. Perinatal
Primary mode in E. Asia and SE Asia
2. Horizontal Transmission Infancy/Childhood
Primary mode in Africa
Close contact within households, medical procedures
3. Sexual
Primary mode of transmission in US
by saliva, vaginal secretions, and semen.
4. Parenteral
Second most common mode of transmission in US

Risk of Perinatal Hep B Transmission
 Positive for HBsAg and HBeAg in the absence of
PEP: (MMWR 2005)
- 70%-90% of infants get infected
 Positive for HBsAg only:
<10% of infants infected

Perinatal HBV Transmission Rates
Without
immunoprophylaxis
HBIG and HBV
vaccine series
HBeAg positive 70-90% 5-10%
HBeAg negative 10-40% <5%

 Role of maternal HBV DNA (Role of maternal HBV DNA (2828wks) onwks) on
transmisiontransmision
Measurement of viral DNA has replacedMeasurement of viral DNA has replaced eAgeAg as theas the
most sensitive test of viral activity.most sensitive test of viral activity.
–– HBV DNA <HBV DNA < 101088 copies/mL=copies/mL= 00% transmission% transmission
–– HBV DNA >HBV DNA > 101088 copies/mL=copies/mL= 3232% transmission% transmission
World J GastroenterolWorld J Gastroenterol 20042004;; 1010:: 32153215––77..

 In utero (<10%)1
––TransplacentalTransplacental viral infection is uncommonviral infection is uncommon
{viral DNA is rarely found in{viral DNA is rarely found in amnionicamnionic fluidfluid
or cord blood}or cord blood}
(Towers et al, 2001).
–Associated with
Acute HBV in 3rd trimester
Maternal HBeAg and high HBV DNA
History of threatened preterm labor
HBV in the placenta

 At the time of delivery1
––Most neonatal infection is verticallyMost neonatal infection is vertically
transmitted bytransmitted by peripartumperipartum exposureexposure
 After birth
–Breastfeeding not associated with
transmission 2
–May be related to scarification, other
parenteral exposures
1. Gambarin-Gelwan Clinics Liv Disease 2007 2. Beasley
Lancet 1975

How to minimize the risk of
transmission ?
I. Antivirals to suppress HBV in mother
(reduce vertical transmission)
II. Post Exposure Prophylaxis (PEP) to
infant

Drug Pregnancy Category
IFN alfa-2b C
PegIFN alfa-2a C
Adefovir C
Entecavir C
Lamivudine (Epivir) C
Telbivudine (Tyzeka) B
Tenofovir (Viread) B
Drugs [package insert].
I. Antivirals

 Lamivudine
100100 mg/daymg/day
From 28 t0 32 w
in patients with HBV DNA > 108 copies/m
Decreased transmission from 28.0% to 12.5%
No adverse events
No complete prevention of transmission, even in
case of successful LAM treatment
(van Zonneveld M, et al. J Viral Hepat. 2003;10:294-297).

 10 RCTs
Shi Obstet Gynecol 2010;116:147–59

TelbivudineTelbivudine ((TyzekaTyzeka))
600mg/d
From 28-32 w
Han G, 2010

II. Prevention of HBV Transmission by =
Post Exposure Prophylaxis (PEP)Post Exposure Prophylaxis (PEP)
 Active plus passive immunization:
most effective to prevent vertical transmission
protective efficacy of 95%
No Vaccine Passive
Immunization
Passive + Active
Immunization
Infants without HBV, % 5 72 95
1. Ranger-Rogez S, et al. Expert Rev Ant Infect Ther. 2004;2:133-145.
2. USPSTF, Screening for Hepatitis B infection. Recommendation statement 2004Aboubakr ElnasharAboubakr Elnashar

 Mode of delivery
has No effect on HBV transmissionhas No effect on HBV transmission
(Yang J, et al. 2008)
 Breast feeding
Although virus is present in breast milk, theAlthough virus is present in breast milk, the
incidence of transmission is not lowered byincidence of transmission is not lowered by
formula feeding: All Neonates who are correctlyformula feeding: All Neonates who are correctly
immunized can beimmunized can be breast-fed
(Cornberg et al, 2008)

High-risk mothers who are seronegative
CDC, 2010
Vaccine can be given during pregnancy.
Her husband infected with hepatitis B,
household contacts of people infected with hepatitis
B
Jobs that expose them to human blood or other
body fluids
travel to countries where hepatitis B is common
Chronic liver or kidney disease,
kidney dialysis patients
Diabetes
HIV infection.

Recommendations for HBV-Infected
Women Who Desire Pregnancy
 Mild liver disease, lowMild liver disease, low viremiaviremia:: Pregnancy beforePregnancy before
treatmenttreatment
 Moderate liver disease, no cirrhosis: TreatmentTreatment
before pregnancy; if response, stop treatmentbefore pregnancy; if response, stop treatment
before pregnancybefore pregnancy
 Advanced liver disease: Treatment before andTreatment before and
during pregnancy; continue treatment afterduring pregnancy; continue treatment after
deliverydelivery
Wedemeyer H, et al. Dtsch Med Wochenschr. 2007;132:1775-1782.
EASL Clinical Practice Guidelines. J Hepatol.
ManagementLiver disease
Treatment before and during
pregnancy; continue treatment
after delivery
Advanced
Treatment before pregnancy; if
response, stop treatment before
pregnancy
Moderate, no cirrhosis
Treatment in last trimester with
“B” category drug with post-
partum discontinuation
Mild , very high
viraemia
Pregnancy before treatmentMild, low viraemia

Algorithm for management of HBV
Pregnant woman
First trimester: HBsAg
HBsAg (-ve)
High risk: maternal HBV
vaccination
Infant receives
vaccine at birth
HBsAg (+)
28 wks
HBV DNA
< 108 copies/mL
Infant receives HBIg
+ vaccine at birth
HBV DNA
> 108 copies/mL
? treatment with
lamivudine at 32
wks
CLEVELAND J OF MEDICINE (76) MAY 2009

Take Home Message
 Perinatal is the most common mode of transmission
 Best prevention for transmission is active/passive
immunization
 PerinatalPerinatal transmission occurs despite appropriatetransmission occurs despite appropriate
infant passiveinfant passive--active immunizationactive immunization
 AntepartumAntepartum antiviral therapy can prevent MTCTantiviral therapy can prevent MTCT
 Neonates that are correctly immunized can beNeonates that are correctly immunized can be
breastbreast--fedfed

Sex partners of HBsAg-positive persons
CDC2010
should be counseled to use methods
(e.g., condoms) to protect themselves from sexual
exposure to infectious body fluids (e.g., semen and
vaginal secretions),
unless they have been demonstrated to be
immune after vaccination (anti-HBs >10 mIU/mL)
or
previously infected (anti-HBc positive).

Thank you
Aboubakr elnashar

Management of HBsAg-Positive Persons CDC
To verify the presence of chronic HBV infection
1. HBsAg-positive persons should be retested.
2. Absence of IgM anti-HBc or the persistence of
HBsAg for 6 months indicates chronic HBV
infection.
Persons with chronic HBV infection should be
referred for evaluation to a physician experienced in
the management of CLD.
1. Some patients with chronic hepatitis B will
benefit from early intervention with antiviral
treatment or
2. screening to detect HCC at an early stage.

Household, sexual, and needle-sharing contacts
of chronically infected persons should be identified.
Unvaccinated sex partners and household and
needle-sharing contacts should be tested for
susceptibility to HBV infection and should receive
the first dose of hepatitis B vaccine immediately
after collection of the blood sample for serologic
testing. Susceptible persons should complete the
vaccine series by using an age-appropriate vaccine
dose and schedule. Persons who are fully
vaccinated should complete the vaccine series.

To prevent or reduce the risk for transmission to
others
1. HBsAg-positive persons should be advised
concerning the risk for transmission to
household, sexual, and needle-sharing contacts
and the need for such contacts to receive
hepatitis B vaccination.
2. HBsAg-positive persons also should be advised
to use methods (e.g., condoms) to protect
nonimmune sex partners from acquiring HBV
infection from sexual activity until the partner
can be vaccinated and immunity documented;
3. cover cuts and skin lesions to prevent the
spread of infectious secretions or blood;

4. refrain from donating blood, plasma, body
organs, other tissue, or semen; and refrain from
sharing household articles (e.g., toothbrushes,
razors, or personal injection equipment) that
could become contaminated with blood.

To protect the liver from further harm
1. HBsAg-positive persons should be advised to
avoid or limit alcohol consumption because of
the effects of alcohol on the liver;
2. refrain from starting any new medicines,
including OTC and herbal medicines, without
checking with their health-care provider; and
3. obtain vaccination against hepatitis A if liver
disease is determined to be present.

When seeking medical or dental care, HBsAg-
positive persons should be advised to inform those
responsible for their care of their HBsAg status so
that they can be appropriately evaluated and
managed.
HBV is not spread by hugging, coughing, food or
water, sharing eating utensils or drinking glasses, or
casual contact.
Persons should not be excluded from work, school,
play, child care, or other settings because they are
infected with HBV.

Hepatitis B in Pregnancy

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