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HEPATITIS IN PREGNANCY

Obstetrics & Gynaecology Lecture | Undergraduate Level | ~30 minutes

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LEARNING OBJECTIVES

1. List the hepatitis viruses relevant to pregnancy and their routes of transmission
2. Explain the maternal and fetal consequences of each type
3. Describe the serological markers for hepatitis B diagnosis
4. Outline the management and preventive strategies for each type in pregnancy
5. Recognise which types carry the highest maternal mortality risk in pregnancy

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SECTION 1 - INTRODUCTION & OVERVIEW (3 min)

• ROSEN's Emergency Medicine; Sleisenger & Fordtran's GI and Liver Disease

• Pregnancy induces relative immune tolerance (to protect the fetus)
• This partial immunosuppression can alter the severity of some viral hepatitides
• Hepatic blood flow and enzyme activity change during normal pregnancy - ALT, AST, and bilirubin should remain within normal limits; alkaline phosphatase rises (due to placental isoform)

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SECTION 2 - HEPATITIS A IN PREGNANCY (4 min)

• Prodrome: malaise, headache, fatigue, anorexia, nausea, vomiting, diarrhea
• Jaundice phase: acholic (pale) stools, dark urine, right upper quadrant discomfort
• Children may be asymptomatic; adult infection tends to be symptomatic
• Self-limited; no chronic state

• HAV does not appear to alter the normal course of pregnancy
• Pregnancy does not appear to influence the natural history of HAV
• Rare severe cases may precipitate premature labour
• Sleisenger & Fordtran's GI and Liver Disease

• Supportive: rest, hydration, antiemetics
• No antiviral therapy
• Hospitalise if unable to maintain oral intake

• HAV vaccine: safe in pregnancy (inactivated)
• HAV immunoglobulin: indicated post-exposure in pregnancy
• Hygiene measures: handwashing, safe food and water

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SECTION 3 - HEPATITIS B IN PREGNANCY (10 min) (most important section)

• HBV infection in pregnant women is the most important factor perpetuating the worldwide epidemic of chronic hepatitis B
• Vertical transmission is responsible for most cases of chronic HBV in endemic areas (Southeast Asia, Africa)
• Universal HBV screening in all pregnant women is recommended
• Sleisenger & Fordtran's GI and Liver Disease

3a. Routes of Perinatal Transmission

• Intrapartum (most common): During delivery - neonatal immune system cannot clear the virus
• Transplacental (in utero): Less common; risk increases if maternal HBV DNA ≥ 7 log copies/mL
• Postpartum: Breast milk (minimal additional risk if infant prophylaxed)
• Invasive procedures (amniocentesis): pose a transmission risk if maternal viral load is very high

3b. Maternal Infectivity & Fetal Risk

• HBeAg-positive mothers: ~90% of exposed infants develop chronic HBV
• HBeAg-negative (HBeAb-positive) mothers: ~10% of infants develop chronic HBV
• Risk is proportional to maternal viral load (HBV DNA level)

3c. Serological Markers (Key Teaching Point)

3d. Effect on Pregnancy

• Most pregnant women with chronic HBV are healthy carriers
• A hepatitis flare (and rarely acute liver failure) may occur in the peripartum period
• ~25% of women with chronic HBV have disease flares in the first few months postpartum
• Increased incidence of spontaneous preterm birth associated with HBV DNA in umbilical cord blood
• Monitor closely for up to 6 months postpartum

3e. Antiviral Therapy in Pregnancy

• Indication: Third-trimester antiviral therapy recommended when HBV DNA >200,000 IU/mL in women with inactive hepatitis B
• Drug of choice: Tenofovir Disoproxil Fumarate (TDF) - preferred due to reliable efficacy and high barrier to viral resistance
• TDF in third trimester significantly reduces mother-to-child transmission
• No significant increase in prematurity, congenital malformations, or low Apgar scores
• Interferon is contraindicated in pregnancy
• Lamivudine and telbivudine have been studied but TDF is preferred
• A 2024 meta-analysis found Tenofovir Alafenamide (TAF) comparable or superior to TDF for preventing vertical transmission with fewer renal/bone side effects (PMID 38805690)

3f. Neonatal Prophylaxis (high yield)

• Infants of all HBsAg-positive mothers should receive:
  1. Hepatitis B Immunoglobulin (HBIG) - within 12 hours of birth
  2. Hepatitis B vaccine - first dose within 12 hours of birth (with subsequent doses at 1 and 6 months)
• This combined passive-active immunoprophylaxis is >95% effective
• However, 1-2% of treated infants still develop chronic HBV (breakthrough infection)
• Breastfeeding is NOT contraindicated as long as the infant has received immunoprophylaxis

3c. Key Message:

Untreated vertical HBV transmission leads to 90% chronicity in the infant - chronic HBV then carries lifelong risk of cirrhosis and hepatocellular carcinoma.

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SECTION 4 - HEPATITIS C IN PREGNANCY (5 min)

• Chronic hepatitis C may be independently associated with adverse pregnancy outcomes (gestational diabetes, preterm birth, low birth weight)
• Population studies have had inconsistent results regarding overall pregnancy outcomes
• Pregnancy does not significantly alter progression of HCV

• Occurs in approximately 5% of infants born to HCV-RNA-positive mothers
• Risk rises to ~10-20% if mother is also HIV co-infected
• Mode of delivery does not clearly reduce transmission
• Breastfeeding is generally NOT contraindicated (very low transmission risk via breast milk) - unless nipples are cracked/bleeding

• Screen with anti-HCV antibody
• Confirm with HCV RNA (PCR) - also determines viral load
• All pregnant women should be screened at least once per pregnancy (CDC recommendation)

• No antiviral therapy during pregnancy - Direct-acting antivirals (DAAs, e.g., sofosbuvir/ledipasvir) are not recommended in pregnancy (insufficient safety data)
• Treatment should be deferred until after delivery and breastfeeding cessation
• Neonatal testing: test infant HCV RNA at 2-6 months or anti-HCV after 18 months

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SECTION 5 - HEPATITIS D (DELTA) IN PREGNANCY (2 min)

• Coinfection: Simultaneous acute HBV + HDV (usually self-limited)
• Superinfection: HDV in chronic HBV carrier (more severe, higher chronicity)

• No evidence that pregnancy changes the natural course of hepatitis D
• Risk is mainly tied to severity of underlying HBV
• Prevention: HBV vaccination prevents HDV (as HDV cannot replicate without HBV)

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SECTION 6 - HEPATITIS E IN PREGNANCY (4 min) (clinically critical)

• Partial immunosuppression during pregnancy may allow more fulminant disease
• HEV genotypes 1 and 2 primarily cause epidemic disease during monsoon season

• Acute HEV in the third trimester is a cause of fulminant hepatic failure
• Maternal mortality rate: up to 20-30% (compared to ~1% in non-pregnant individuals)
• Washington Manual of Medical Therapeutics; Sleisenger & Fordtran's GI and Liver Disease

• Intrauterine fetal death
• Increased risk of miscarriage and abortion in any trimester
• Vertical transmission of HEV to neonate resulting in symptomatic neonatal hepatitis has been documented
• No known therapy to prevent vertical transmission

• Supportive care
• ICU admission for fulminant hepatic failure
• Urgent delivery may be required if hepatic failure develops
• Liver transplant evaluation if no recovery

• Avoid traveling to endemic areas during monsoon season and outbreaks
• HEV vaccine (HEV 239) approved in China - not yet approved in most other countries
• Safe water supply; handwashing

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SECTION 7 - SUMMARY TABLE (2 min)

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SECTION 8 - CLINICAL PEARLS / HIGH YIELD POINTS (2 min)

1. Hepatitis E carries the highest mortality in pregnancy (up to 30%) - especially in the third trimester in endemic areas (South Asia, India).
2. HBV is the most clinically significant in terms of long-term neonatal consequences - 90% of HBeAg+ mother's infants develop chronic HBV without intervention.
3. HBIG + HBV vaccine within 12 hours of birth is the cornerstone of preventing vertical HBV transmission.
4. TDF is the antiviral of choice when antiviral therapy is needed in pregnancy for HBV.
5. Interferon is absolutely contraindicated in pregnancy.
6. HCV vertical transmission rate is ~5% (rises to ~10-20% with HIV coinfection).
7. Hepatitis A and E are both fecal-orally transmitted - but their pregnancy consequences are vastly different.
8. A postpartum HBV flare occurs in ~25% of women with chronic HBV in the first few months after delivery - follow up is essential.
9. Alkaline phosphatase is normally elevated in pregnancy (due to placental isoform) - do not misinterpret as liver disease.
10. Screen ALL pregnant women for HBsAg and HCV at the first antenatal visit.

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SECTION 9 - SAMPLE MCQS / VIVA QUESTIONS (2 min)

A: Start tenofovir disoproxil fumarate (TDF) to reduce vertical transmission risk

A: Hepatitis E virus (HEV)

A: HBIG AND hepatitis B vaccine (first dose)

A: Anti-HBc IgM (HBsAg has disappeared; HBsAb not yet detectable)

A: None of the above - breastfeeding is safe with all hepatitis viruses, with appropriate neonatal prophylaxis for HBV

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REFERENCES / FURTHER READING

• Creasy & Resnik's Maternal-Fetal Medicine: Principles and Practice - Chapter 64 (Viral Hepatitis in Pregnancy)
• Sleisenger & Fordtran's Gastrointestinal and Liver Disease - Chapter on Pregnancy and Liver Disease
• Yamada's Textbook of Gastroenterology - Liver Diseases Concurrent with Pregnancy
• Goldman-Cecil Medicine - Liver Disease in Pregnancy
• Pan CQ et al. (2024). TAF vs TDF for preventing vertical HBV transmission - Clin Infect Dis (PMID 38805690, meta-analysis)
• Afraie M et al. (2023). HBV effect on pregnancy outcomes - Virol J (PMID 37710321, meta-analysis)

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