MANAGEMENT OF HBV AND HCV IN

PREGNANCY
ULFA KHOLILI, , dr., Sp.PD, K-GEH, FINASIM
 INTRODUCTION
 It has been estimated that up to 29,000 HCV-infected women
gave birth each year from 2011 to 2014.

 Up to 8% of pregnant women are infected with Hepatitis C

virus (HCV) 3

3 HCV in Pregnancy.; 2014. www.HCVGuidance.org

 WHAT IS NATURAL COURSE OF HCV?

ACUTE CHRONIC
The first 6 months after Asymptomatic, although it can
exposure to HCV. cause progressive liver damage
with serious consequences.

Asymptomatic in 75% of 15-30% of patients with chronic

cases; when symptoms occur, HCV infection develop cirrhosis
they include abdominal pain, within 20 years.
nausea, anorexia, jaundice, or
malaise. 27% of those with cirrhosis
develop hepatocellular carcinoma
15% of infected individuals (HCC) within 10 years.
spontaneously clear HCV
within 6 months of infection. HCC is a primary cause of
mortality from HCV infection.
Brenna L. Hughes et al. 2017. Hepatitis C in pregnancy: screening, treatment, and
management. Society for Maternal-Fetal Medicine (SMFM) Consult Series
WHO SHOULD BE SCREENED FOR HCV DURING
PREGNANT ?

Society for Maternal – Fetal Medicine. HCV pregnancy. Am J Obstet Gynecol 2017
WHAT IS THE IDEAL SCREENING TEST
FOR HCV ?

http://www.cdc.gov/immwr/pdf/wk/mm62e0507a2.pdf
 WHOM TO TREAT?

There are no large-scale clinical trials evaluating the safety of

direct-acting antivirals (DAAs) in pregnancy. A small study
evaluating the pharmacokinetics of sofosbuvir in pregnancy
demonstrated 100% SVR12 and no safety concerns(Chappell,
2019).

3 HCV in Pregnancy.; 2014. www.HCVGuidance.org

 WHOM TO TREAT?
 Women of reproductive age with HCV should be
counseled about the benefit of antiviral treatment prior to
pregnancy to improve the health of the mother and
eliminate the low risk of mother-to-child transmission
(MTCT).

 Women who become pregnant while on DAA therapy

(with or without ribavirin) should discuss the risks versus
benefits of continuing treatment with their physicians.

 Ribavirin is contraindicated in pregnancy due to its known

teratogenicity.
3 HCV in Pregnancy.; 2014. www.HCVGuidance.org
MONITORING DURING PREGNANCY

3 HCV in Pregnancy.; 2014. www.HCVGuidance.org

 IMPACT OF PREGNANCY ON HCV
 In general, serum ALT levels decrease during the first
and third trimesters of pregnancy and increase after
delivery.

 HCV RNA levels rise during the first and third

trimesters, reaching a peak during the third trimester,
and decrease postpartum

 Down-regulation of the maternal immune

response in pregnancy  reduce the amount of
hepatocellular damage caused by HCV, which would also
account for the decrease in ALT levels.
3 HCV in Pregnancy.; 2014. www.HCVGuidance.org
 IMPACT OF HCV ON PREGNANCY
 Infants born to women infected with HCV were
more likely to be small for gestational age, have
low birth weight, require admission to the
neonatal intensive care unit, and require
assisted ventilation.

 HCV-infected women were more likely to deliver

infants with poor birth outcomes, including
preterm birth, low birthweight, and congenital
anomalies.

3 HCV in Pregnancy.; 2014. www.HCVGuidance.org

 TREATMENT AND OUTCOMES

 For pregnant women with confirmed active HCV infection:

 A quantitative HCV RNA test should be done to
determine the baseline viral load.
 Basic laboratory testing to evaluate the extent of liver
disease: bilirubin, ALT, and AST, albumin, platelet
count, and prothrombin time and HCV genotype.

 We recommend that obstetric care providers screen HCV-

positive pregnant women for other sexually transmitted
diseases, including HIV, syphilis, gonorrhea, chlamydia, and
hepatitis B virus (HBV) (GRADE 1B).

3 HCV in Pregnancy.; 2014. www.HCVGuidance.org

 TREATMENT AND OUTCOMES

 None of the antiviral therapies recommended for HCV

infection are currently approved for use in pregnant women.

 Ribavirin is contraindicated in pregnancy (embryocidal and/or

teratogenic effects in all animal species studied).

 Ribavirin can persist in nonplasma compartments for up to 6

months ( FDA recommends pregnancy should be avoided in women
taking ribavirin as well as in female partners of male patients taking
ribavirin until 6 months after completing therapy.

 At least 2 forms of effective contraception be used during treatment

(of either the male or female partner) and for 6 months afterwards
to prevent pregnancy.
3 HCV in Pregnancy.; 2014. www.HCVGuidance.org
 TREATMENT AND OUTCOMES

 Due to the lack of human studies, no DAA therapy has yet

been approved to treat HCV infection in pregnancy.

 The FDA has not categorized most of these drugs in

terms of pregnancy safety.
 Although limited animal data are available, sofosbuvir and
ombitasvir/paritaprevir/ritonavir have not been
demonstrated to confer a risk to the fetus.
 Simeprevir has shown fetal toxicity in animal studies.

3 HCV in Pregnancy.; 2014. www.HCVGuidance.org

 TREATMENT AND OUTCOMES

 Ribavirin free DAA regimens for use in pregnancy

should be actively researched.

 DAA regimens only be used in the setting of a clinical

trial or that antiviral treatment be deferred to the
postpartum period as DAA regimens are not
currently approved for use in pregnancy (GRADE
1C).

3 HCV in Pregnancy.; 2014. www.HCVGuidance.org

TREATMENT AND OUTCOMES
 SUMMARY OF RECOMMENDATIONS

Brenna L. Hughes et al. 2017. Hepatitis C in pregnancy: screening, treatment, and

management. Society for Maternal-Fetal Medicine (SMFM) Consult Series
HBV IN PREGNANCY
 INTRODUCTION
 Worldwide, some 240 million people have chronic hepatitis B
virus (HBV), with the highest rates of infection in Africa and
Asia.

 Management of HBV infection in pregnancy is difficult because

of several peculiar and somewhat controversial aspects.

 Globally, in 2015, chronic HBV (measured by sero prevalence

of HBsAg) was estimated to affect 3.5 percent of the
population (approximately 257 million individuals) including an
estimated 65 million women of childbearing age.

Lampertico P. EASL HBV Guidelines 2017.

 Hepatitis B virus (HBV) infection poses a significant
global health problem with an estimated 350-400
million chronically infected individuals worldwide.

EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection Q.
  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).

EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection Q.
 Clinical Picture

 Most infections during pregnancy: chronic,

asymptomatic
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.

Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the
management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1-98.
doi:10.1007/s12072-015-9675-4
 Hepatitis B Lab Markers

 HBsAg : Marker of current infection

 HBeAg : Marker of active replication,
Identification of persons at increased risk for
transmitting HBV
 HBV DNA : Viral load
 Anti-HBs : marker of resolved infection /immunity
after immunization
 Anti-Hbe : Identification of person with lower risk
for transmitting HBV
Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the
management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1-98.
doi:10.1007/s12072-015-9675-4
 Pregnancy and HBV

EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection Q.
 Algorithm for management of HBV
Pregnant woman

First trimester : HBSAg

HBsAg (-) HBsAg (+)

High risk : maternal HBV

vaccination HBV DNA HBV DNA
<10 8 copies/mL >10 8 copies/mL
Infant receives
vaccine at birth Infant receives Treatment with
HBIg + vaccine lamivudine at
at birth 32 weeks

EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection Q.
 Algorithm for management of HBsAg-positive

Norah A. Terrault.2018. Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018
Hepatitis B Guidance. Hepatology, Vol.67, No. 4
 Algorithm for management of HBsAg-
positive

Norah A. Terrault.2018. Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018
Hepatitis B Guidance. Hepatology, Vol.67, No. 4
 Impact of HBV on Pregnancy

 Gestationaldiabetes
 Lower APGAR scores
 Preterm delivery

 Liver disease:
No worsening of liver disease in majority of women
Case reports of hepatic exacerbations/ fulminant hepatic
failures

EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection Q.
 SCREENING AND CONSELING OF HBV IN
PREGNANT WOMEN
 All pregnant women should be screened for HBsAg.

 Antiviral therapy in the third trimester is

recommended for pregnant women with serum HBV
DNA >200,000 IU/mL.

 Supporting the AASLD guideline recommendation that

antiviral therapy given for prevention of mother-to-
child transmission be discontinued at the time of
delivery or up to 4 weeks postpartum.

EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection Q.
 SCREENING AND CONSELING OF HBV IN
PREGNANT WOMEN
 A previous systematic review of any antiviral therapy in
the third trimester showed a significant reduction in
perinatal transmission of HBV with lamivudine,
telbivudine, or TDF.

 but TDF is the preferred choice owing to its antiviral

potency and concerns for resistance with the other
antiviral agents.

EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection Q.
 Guidance Statements on Counseling of
Women inPregnancy
 HBV vaccination is safe in pregnancy, and pregnant women
who are not immune to or infected with HBV should receive this
vaccine series.

 Women identified as HBsAg positive during pregnancy

should be linked to care for additional testing (ALT, HBV
DNA, or imaging for HCC surveillance if indicated) and
determination of need for antiviral therapy.

 Women who meet standard indications for HBV therapy should

be treated. Women without standard indications but who have
HBV DNA >200,000 IU/mL in the second trimester should
consider treatment to prevent mother-to-child transmission.

EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection Q.
 Guidance Statements on Counseling of
Women inPregnancy
 HBV-infected pregnant women with cirrhosis should be
managed in high-risk obstetrical practices and treated
with TDF to prevent decompensation.

 Sexual partners of women identified as HBVinfected

during pregnancy should be assessed for HBV infection or
immunity and receive HBV vaccine if appropriate.

 Breastfeeding is not prohibited.

EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection Q.
How to minimize the risk of transmission?

I. Antivirals to suppress HBV in mother (reduce

vertical transmission)

II. Post Exposure Prophylaxis (PEP) to infant

EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection Q.
ANTIVIRALS
Lamivudine
 100 mg/day
 From 28 t0 32 w
 in patients with HBV DNA > 10 8 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
 Telbivudine(Tyzeka)
 600mg/d From 28-32 weeks (Han G, 2010)
ShiObstet Gynecol 2010;116:147–59
 Prevention of HBV Transmission by =
Post Exposure Prophylaxis (PEP)
 Active plus passive immunization: most effective to
prevent vertical transmission protective efficacy of 95%

 Mode of delivery
has No effect on HBV transmission (Yang J, et al. 2008)
 Breast feeding
Although virus is present in breast milk, the incidence of
transmission is not lowered by formula feeding: All
Neonates who are correctly immunized can be breast-fed
(Cornberg et al, 2008)
 REFERENCES
1. Lampertico P. EASL HBV Guidelines 2017.
2. Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific
clinical practice guidelines on the management of
hepatitis B: a 2015 update. Hepatol Int.
2016;10(1):1-98. doi:10.1007/s12072-015-9675-4
3. HCV in Pregnancy.; 2014. www.HCVGuidance.org.

4. EASL 2017 Clinical Practice Guidelines on the

Management of Hepatitis B Virus Infection Q.
THANKYOU