HEPATITIS B IN PREGNANCY

Dr Sudarshan Krishnamurthi
Queen Elizabeth Hospital
OVERVIEW
• Epidemiology
• Natural history of Hep B
• Diagnosis of hip B
• Terminologies used in Hep B
Epidemiology
• Hep B is a global health problem
• 300 million carriers worldwide
• 600 000 die annually from HBV related causes
• Countries > 10% HBV carriers ; causes 3% total mortality
• 80 % of HCC are related to HBV

Hepatitis B: global importance and need for control. Maynard JE ; Vaccine. 1990;8 Suppl:S18.
Transmission of HBV

Vertical

IVDU Horizontal

HBV

Transplant Sexual

Transfusion
Natural history of HBV
• Double stranded DNA virus
• Incubation period ; 180 days
Clinical Manifestation

Acute Chronic
hepatitis hepatitis

HBV
Acute hepatitis
• 70 % patients are asymptomatic (anicteric)
• Risk of fulminant hepatitis ; 0.5 %
• 1-4 months
• ALT/AST raised ; PT indicator of prognosis
• OUTCOME
• Vertical transmission ; 90 %1 progress to chronic hepatitis
• Horizontal transmission : 20-50 % 2

• Adult acquired infections : 5 % 3

1. Vertical transmission of hepatitis B antigen in Taiwan. Stevens CE, N Engl J Med. 1975;292(15):771.
2. Incidence of hepatitis B virus infections in preschool children in Taiwan. Beasley RP J Infect Dis. 1982;146(2):198.
3. Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults :Tassopoulos ; Gastroenterology. 1987;92(6):1844.
Sequelae of chronic hepatitis B
• Chronic hepatitis to cirrhosis ;12-20%
• Compensated cirrhosis to decompensated ;20%
• Compensated cirrhosis to HCC: 6-15%

Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors :Fattovich G J Hepatol. 2008;48(2):335.
Diagnosis of Hep B
• Who should we screen ?

Lok ASF, McMahon BJ. Chronic hepatitis B: Update 2009. Hepatology 2009; AASLD
Serologic markers
• HBsAg : current infection ;persistence >6 month –chronic
infection
• Anti HBs : resolved infection/immunity
• HBeAg :marker of active replication
• Identifies persons at inc risk of transmission
• AntiHB e :person at lower risk of transmission
• HBcAb; Acute hepatitis ; IgM-HBc
• Viral Load ( HBV DNA) : assess HBV replication and
candidacy for tx
Hep B in Pregnancy
• 1.Introduction
• 2.Spectrum of disease
• 3.Mother-child transmission
• 4.Management of CHB in pregnancy
• 5.Prevention of mother child transmission
Introduction
• Prevention of vertical transmission is an important global
effort
• AIM : reduce burden of HBV infection
• Vertical transmission : responsible for half of Hep B
infections worldwide
• Without vaccination > 90 % of vertical transmission
progress to chronic hep B
• Maternal screening & universal vaccination of infants
;reduced transmission rates
Spectrum of disease
• Acute Hep B
• Most common cause of jaundice in pregnancy
• Usually self-limiting
• Can cause low birth weight & prematurity1
• Transmissions rates depend on time of infection
• Early pregnancy ; 10 %
• At time of delivery : 60 %
• Treatment ;supportive
• Antiviral if high viral DNA in 3rd trimester
• Infants ; HBIG and hep B vaccine

1. Hepatitis and pregnancy.; Hieber JP, J Pediatr. 1977;91(4):545

 Chronic hepatitis

Maternal disease Pregnancy

Effect on Maternal disease
• Pregnancy well tolerated unless patients have CLD
• High levels of corticosteroids in pregnancy may affect
immune response in CHB
• Hepatic flares ; HBeAg + patients1 ; risk 1.5 % during
pregnancy , 25 % during post-partum period
• Progression of liver disease ; rare ; natural progression
takes time .
• Flares may accelerate progression
• Normal physiologic changes in pregnancy can mimic (
drop in albumin , raised ALP AFP )
• HBV DNA ; stable during pregnancy2
1. Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B. Giles M Gut. 2015 Nov;64(11)
2. Hepatitis B virus DNA during pregnancy and post partum: aspects on vertical transmission Söderström A, Scand J Infect Dis. 2003;35(
Effect on pregnancy
• If NO cirrhosis ; NO effect1 on birth weight, prematurity,
congenital abnormalities, neonatal jaundice , perinatal
mortality
• Cirrhosis : inc. risk of complications2 e.g. IUGR, preterm
delivery , gestational hypertension, placenta abruptio,
• Progression of decompensation in cirrhotic mothers
• Variceal bleeding inc esp. in 3rd trimester

1. Hepatitis B carrier and perinatal outcome in singleton pregnancy. Wong S Am J Perinatol. 1999;
2. The outcomes of pregnancy in patients with cirrhosis: a population-based study. Shaheen AA Liver Int. 2010 Feb;30(2
Management of CHB in pregnancy
• Need to consider
• 1.indication
• 2.duration of therapy
• 3.potential adverse events to fetus
• 4.cost and accessibility of anti-virals

• Patients should be referred to hepatologist for co-

management
• NOT all pregnant women require treatment
• Pregnant while on antiviral
• Inform clinician immediately
• Need to discuss risk and benefits with patient
• Treatment strategy
• 1. if no cirrhosis ; can consider withholding
• 2.switch to tenofovir ; if on entecavir, adefovir , or IFN
Indication for antiviral during pregnancy
• Decision to treat based on presence of cirrhosis, HBeAg,
HBeAb , ALT , Viral load
• Indication for antiviral same as those non-pregnant
• HBeAg + ve ; VL > 20000 , ALT > 2x ULN
• HBeAg –ve : VL > 2000 , ALT > 2x ULN

• Some caveats : can defer if no cirrhosis , despite high VL

or ALT ( borderline high)
• Anti-viral started at 3rd trimester ; to prevent perinatal
transmission
• Tenofovir preferred agent
Women without indication for antiviral
• Monitor closely for flares
• Monitor LFT’s 3monthly during pregnancy and extend to 6
month post partum
• HBV DNA ; if any elevation of ALT
• HBV DNA at week 26-28 ; to decide if antiviral for
peripartum prophylaxis
Cirrhotic patients
• Antiviral to reduce risk of progression
• Variceal screening ; OGDS safe in pregnancy
• Variceal bleed ; tx with EVL , sclerotherapy
• Octretide : avoid can cause uterine ischemia
• B-Blockers ; IUGR , fetal bradycardia,neonatal
hypoglycemia
Women planning on pregnancy
• Need for treatment determined by HBeAg status, Viral
load , stage of liver disease (cirrhotic, ALT )
• 2 strategies
• 1. Defer treatment ; till family complete
• If no evidence of cirrhosis
• 2.treat before pregnancy
• IFN preferred ; finite duration ( 48 weeks) ; advise on
barrier contraception
• Tenofovir is the alternative
Breastfeeding
• Can breastfeed once infants receive first dose of HBIG
and Hep B vaccine
• Mothers exercise care ; avoid bleeding (cracked nipples)
• Patients on anti-viral ; drug labels advise to avoid
• Case reports1 : tenofovir maybe safe

1. Tenofovir disoproxil fumarate for prevention of vertical transmission of hepatitis B virus infection by highly viremic pregnant women: a case
series. Pan CQ Dig Dis Sci. 2012 Sep;57(9
Mother to child transmission
• Risk of transmission1 > 90 % without immunization
• Infection occurs during delivery when maternal
blood/fluids came into contact with infants mucous
membranes
• HBIG and hepB vaccine reduce transmission2 = 1 %

1. Vertical transmission of hepatitis B antigen in Taiwan. Stevens CE, N Engl J Med. 1975;
2. Outcomes of infants born to women infected with hepatitis B Schillie S Pediatrics. 2015 May;135(5):
Risk factors for transmission
• 1. HBV replicative status : HepB e Ag + and high viral
load
• Important factor for risk of transmission
• Viral load : > 106 copies /ml ; transmission risk increases
50 % 1

1. Effect of hepatitis B immunoglobulin on interruption of HBV intrauterine infection Li XM World J Gastroenterol. 2004;
Risk of transmission
Risk factors for transmission
• 2. Transplacental : minority of infections
• Placental leakage during threatened abortion
• 3.Amniocentesis : low risk1 esp if mother is e Ag – ve
and , low viral load
• 4.Preterm premature rupture of membranes : limited
data
• 5.Cesarean delivery : no clear benefit 2

1. Chronic viral infections and invasive procedures: risk of vertical transmission and current recommendations. López Fetal Diagn Ther. 2010;
2. Effect of delivery mode on maternal-infant transmission of hepatitis B virus by immunoprophylaxis Wang J Chin Med J (Engl). 2002 Oct;
Prevention of Mother child transmission
• Involves :
• 1. screening mothers
• 2.antiviral for mothers with high infectivity
• 3.passive-active immunization for newborns
Maternal screening
• HBsAg screening in ALL pregnant women during 1st
antenatal visit
• If HBsAG + ; further test ; HBeAg , HBeAb , ALT , HBV
DNA
• Early referral to hepatologist ; high viral load ,HBeAg +,
ALT raised
• May need early antiviral
• Other children /spouse should be tested
Maternal antiviral therapy
• AASLD ; recommends antiviral for mothers with high viral
load in addition to immunization of infants
• If not on treatment
• Repeat viral load at week 26-28 of gestation
• If viral load > 106 copies/ml ; start antiviral ( week 28-30)
• Sufficient time for viral load to decrease before delivery
Choice of antiviral
• 1. Tenofovir : drug of choice
• Safe in pregnancy 1

• Resistance is rare ; important if long term tx required

• 2.Alternative : lamivudine & telbivudive
• Safe in pregnancy but high resistance rates
• Important to discuss about post-partum period (
breastfeeding , risk of flares)

1. Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus Chen HL Hepatology. 2015
Post-partum
• If patient was started for the purpose of reducing perinatal
transmission & planning to breast feed – STOP
• If planning to continue : risk of breast feeding
• Monitor for flares ; LFTs every 3 months for at least 6
months ( regardless of decision on antiviral)
Newborn immunization
• Infants MUST receive passive-active immunization
• HBIG & 1st dose of Hep B vaccine series must be given
within 12 hours of delivery
• Both administered at different sites
Management of Hep B in Pregnancy
Summary
• Vertical transmission important cause of HBV infection
• ALL pregnant mothers must be screen for Hep B
• Baseline work up if HBsAg + ve
• Refer to hepatologist
• Repeat viral load at week 26-28
• If high viremia ; start antiviral
• Newborn : passive + active immunization
• Post partum : monitor for flares