Dr. MOHINISH CHHABRA DM Gastroenterology

SENIOR CONSULTANT

DEPARTMENT OF GASTROENTEROLOGY

FORTIS MULTISPECIALITY, HOSPITAL

MOHALI

Management of hepatitis B in pregnancy

Hepatitis B and pregnancy

• Perinatal transmission of HBV is major mode of transmission worldwide

• Immunoprophylaxis is of proven benefit in prevention of perinatal HBV transmission and is recommended

• High maternal viremia is associated with higher rate of perinatal transmission

• Should treatment be initiated in pregnancy?

Implementation of newborn vaccination world wide 2006 WHO data

HBV prevalence

High > 8%

Intermediate 2-8%

Countries with HBV vaccine birth dose

44%

53%

Case

• 24 yr female presented with incidental detection of HBsAg + during blood donation

• PMH Non contributory• Recently married, no children• Family history unknown• ROS Non contributory• P/E NORMAL

CaseLaboratory

• HBsAg positive

• HBeAg positive

• Anti HBe Negative

• ALT 18, AST 20, AP 100, TSB 0.8

• CBC Normal

• USG abdomen Normal

• HBV DNA 5 x 109 IU/ml

CASE

Phase HBsAg HBeAg Anti-HBe

HBV

DNA

ALT Histology

Immune Tolerant

phase

+ + - >20000 IU/ml

Normal Minimal

activity

Chronic Hepatitis B

+ + - >20000 IU/ml

Elevated

Persist

Moderate or severe inflammation

CASE

• Immune tolerant – Elect not to treat her

• 8 months later she presents with pregnancy

• What to do?

Treatment during pregnancy2 separate issues

• Treatment for woman’s benefit

Why treat now? Advanced disease Already on treatment – concern for withdrawal flare Concern for progression

• Prevention of transmission to infant No clear AASLD guidelines on treatment Risk / benefit of treatment in 3rd TM

HBV DNA level and perinatal transmission of HBV (N=138)

Maternal HBV status

• HBV DNA + • HBeAg +

HBV DNA < 105 copies/ml• 105-108 copies/ml• > 108 copies/ml

Perinatal transmission

• 3%• 7% p = .039

• 0%• 0%• 8.5% p= .031

Wiseman et al, Med J Aust 2009;190:489492

Transplacental spread

• Xu et al 402 HBsAg + pregnant women – 3.7% newborn infants were HBsAg + within 24 hours of birth, HBeAg + mothers intrauterine infection 9.8% , placental infection rate 44%

Xu DZ et al J Med VIROL 2002;67:20-26

• Indian study- 11524 pregnant mothers screened 133 HBsAg +, babies screened for HBsAg, HBeAg, HBV DNA in serum and cord blood- 66% babies positive for HBV DNA in cord blood, 4% positive serum markers. Maternal HBV DNA 1.5 X 105 copies/ml significantly associated with intrauterine transmission

Pande C et al, Abstract 252 DDW May

2008

Hepatitis B and pregnancyTreatment dilemmas

• Transmission risk > 8% is it worth treating the mother during pregnancy?

• Do we know how much treatment will decrease the risk?

• Concern that HBIG + vaccine at birth may not prevent infection in those born already infected supports the need to treat during pregnancy

Third trimester use of Lamivudine reduces the risk of perinatal transmission

Infant outcomes at week 52

Lamivudine

(N=56)• HBsAg + 18%• HBV DNA + 20%• Anti HBs + 84%

Control

(N=59)

39% P= .014

46% P=.003

65% P=.008

Xu WM et al J Virol Hepat 2009;16:94-1003

HBV transmissionTreated vs. Non treated

% of infants HBsAg +

Telbivudine Untreated n= 95 n=92At birth 6.32% 30.43% p=<.001

28 Weeks 2.15% 13.04% p=.004

Han G et al, 615 AASLD 2010

Antiviral agents used for treatment of chronic hepatitis B

Agent Pregnancy category

Adefovir C

Entecavir C

Lamivudine C

Telbivudine B

Tenofovir B

Safety profile of LAM or TDF during pregnancy – The Antiretroviral pregnancy registry study

Birth defect rate

1st TM 2nd/3rd TMAny retroviral 2.8% 2.5%Exposure (n) 4702 6100

LAM 2.9% 2.5%Exposure (n) 3314 5017

TDF 2.4% 1.7%Exposure (n) 756 461

Normal pregnancy 2-3%

CASE

• After discussion of risk/benefits of treatment patient opts for treatment in 3rd TM starting at 32 weeks

• HBV DNA drops by 5 logs by delivery

• Infant receives HBIG/ vaccine within 12 hours

• Mother expresses her desire to breast feed the baby for at least 5 months a) Stop antiviral treatment b) Advise against breastfeeding to minimize the risk of transmission of HBV to newborn c) Continue antiviral given its safety profile in pregnancy d) Switch to Tenofovir/Telbivudine as Pregnancy category B drug

Hepatitis B and breast feeding

• Is HBV transmitted through the breast milk?

• Are anti viral safe to take while breast feeding?

• What is the risk to the mother of discontinuing anti viral during the breast feeding period?

TAKE HOME PEARLS

• Vaccination/ immunoprophylaxis is the MOST important preventive strategy

• Perinatal transmission risk is greatest in those with high maternal viremia : HBV DNA > 8 logs

• Third trimester treatment may reduce the risk of HBV transmission, but data is limited: Risks /benefit to be discussed

• Breast feeding is safe