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Summary Table

Category	Details
Risk Factors	Endemic region origin (Southeast Asia, Sub-Saharan Africa, China), IV drug use, multiple sexual partners, household contact with chronic HBV carrier, healthcare workers, unvaccinated mothers
Etiology	Hepatitis B virus (HBV), a partially double-stranded DNA virus of the Hepadnaviridae family; transmitted vertically (mother-to-child) during delivery through exposure to infected blood and genital secretions
Patient Presentation	Often asymptomatic; identified on routine prenatal screening via HBsAg. Occasionally presents with fatigue, nausea, RUQ discomfort, or jaundice if acute flare occurs during pregnancy
Classic Physical Exam	May be entirely normal. Possible hepatomegaly, mild RUQ tenderness, jaundice and scleral icterus in acute or reactivation flares
Key Diagnostic Results	HBsAg (+) on prenatal screen, HBeAg (+) and high HBV DNA viral load (>200,000 IU/mL) indicate high infectivity and high vertical transmission risk
Management	Antiviral therapy (tenofovir disoproxil fumarate) starting at 28 to 32 weeks if HBV DNA >200,000 IU/mL; newborn receives HBV vaccine + hepatitis B immunoglobulin (HBIG) within 12 hours of birth
Keywords	"Immigrant from endemic area," "routine prenatal HBsAg positive," "HBeAg positive," "high viral load," "birth dose immunoprophylaxis," "tenofovir in third trimester"

1. Pathophysiology

HBV is a partially double-stranded DNA virus that replicates through an RNA intermediate using its own reverse transcriptase. The virus itself is not directly cytopathic. Instead, liver damage results from the host immune response directed against infected hepatocytes displaying viral antigens on their surface. This is why immunotolerant patients (such as those infected perinatally) can carry very high viral loads for decades with minimal liver inflammation, while a robust immune response in adulthood causes more symptomatic hepatitis but also a higher chance of viral clearance.

In pregnancy, the critical concern is vertical transmission, which occurs predominantly during labor and delivery through the neonate's exposure to maternal blood and cervicovaginal secretions. The risk of transmission correlates directly with maternal viral load and HBeAg status. Mothers who are both HBsAg (+) and HBeAg (+) with high viral loads carry a vertical transmission rate of 70 to 90% without intervention. Mothers who are HBsAg (+) but HBeAg (-) have a lower but still notable risk of roughly 10 to 40%.

The reason perinatal infection is so consequential is the inverse relationship between age at infection and chronicity. Neonates infected at birth have a 90% chance of developing chronic HBV infection, compared to roughly 5% in immunocompetent adults. Chronic infection acquired perinatally leads to decades of viral replication, progressive hepatic fibrosis, and a significantly elevated lifetime risk of hepatocellular carcinoma and cirrhosis. This is the foundational rationale behind universal prenatal screening and aggressive neonatal immunoprophylaxis.

Transplacental transmission (in utero) accounts for a smaller fraction of cases and is thought to occur through placental breaches or high-level viremia crossing the placental barrier. This route is less amenable to postnatal immunoprophylaxis alone, which is precisely why maternal antiviral therapy in the third trimester has been added to guidelines for women with very high viral loads.

2. Classification and Clinical Manifestation

HBV Serologic Phases in Chronic Infection

Phase	HBsAg	HBeAg	Anti-HBe	HBV DNA	ALT	Liver Histology	Clinical Significance
Immune Tolerant	+	+	-	Very high (>1 million IU/mL)	Normal	Minimal inflammation	Common in perinatally infected; high infectivity, low disease activity
Immune Active (HBeAg+)	+	+	-	High	Elevated	Active inflammation and fibrosis	Treatment candidate; high transmission risk in pregnancy
Inactive Carrier	+	-	+	Low (<2,000 IU/mL)	Normal	Minimal or no fibrosis	Low transmission risk; monitor for reactivation
HBeAg-Negative Chronic Hepatitis	+	-	+	Moderate to high	Elevated (fluctuating)	Active inflammation	Precore/core promoter mutant; can still transmit vertically
Resolved Infection	-	-	+	Undetectable	Normal	Variable (prior damage may persist)	Anti-HBs (+), Anti-HBc (+); not a transmission risk

3. Diagnostic Workup

Test	Role	Key Finding
HBsAg (prenatal screen)	Best initial test; universal screening at first prenatal visit	Positive = active HBV infection (acute or chronic)
HBeAg	Marker of active viral replication and high infectivity	Positive = high vertical transmission risk
Anti-HBe	Marker of lower replication state	Positive with HBeAg (-) = lower but not zero risk
HBV DNA quantitative viral load	Most accurate test to quantify transmission risk and guide antiviral therapy	>200,000 IU/mL = indication for maternal antiviral therapy
Anti-HBs	Immunity marker	Positive in vaccinated or resolved infection
Anti-HBc IgM	Distinguishes acute from chronic infection	Positive = recent or acute infection
Anti-HBc IgG	Marker of prior exposure (present in both chronic and resolved)	Positive in any past or present HBV exposure
Hepatic function panel (ALT/AST)	Assess degree of liver inflammation	Elevated ALT suggests immune-active disease
Liver ultrasound	Evaluate for cirrhosis or hepatocellular carcinoma in chronic carriers	Nodular liver, splenomegaly, or focal lesions prompt further evaluation

HBsAg is the universal prenatal screening test and is recommended for all pregnant women at the first prenatal visit, regardless of vaccination history or prior testing. This is the single most important step and the one most commonly tested. A positive HBsAg triggers the full serologic workup.

Once HBsAg is confirmed positive, the next step is to check HBeAg, Anti-HBe, and a quantitative HBV DNA viral load. The viral load is the key decision point for antiviral therapy. ALT should also be obtained to determine whether the patient is in an immune-active phase. If ALT is elevated and the patient has not been previously evaluated, hepatology or infectious disease referral is appropriate.

A common exam scenario presents a woman who was vaccinated but still tests HBsAg (+). This tests your understanding that the vaccine contains only recombinant HBsAg protein and produces Anti-HBs antibodies. A vaccinated person should be HBsAg (-) and Anti-HBs (+). If HBsAg is positive, the patient has true infection, not a vaccine artifact.

For women with unknown HBsAg status at the time of delivery, rapid HBsAg testing should be performed, and the neonate should receive the HBV vaccine birth dose within 12 hours regardless. HBIG should be administered as soon as the maternal result returns positive (and no later than 7 days of life).

4. Management and Treatment

Clinical Scenario	Maternal Intervention	Neonatal Intervention	Breastfeeding
HBsAg (+), HBeAg (-), DNA <200,000 IU/mL	Monitor; no antiviral needed in pregnancy	HBV vaccine dose 1 + HBIG within 12 hours of birth	Permitted after immunoprophylaxis
HBsAg (+), HBeAg (+), DNA >200,000 IU/mL	Tenofovir disoproxil fumarate (TDF) 300 mg daily starting at 28 to 32 weeks gestation	HBV vaccine dose 1 + HBIG within 12 hours of birth	Permitted after immunoprophylaxis
Acute HBV flare in pregnancy with liver failure	Supportive care, antiviral therapy (TDF), hepatology consultation; consider early delivery if severe	HBV vaccine dose 1 + HBIG within 12 hours of birth	Case-by-case
HBsAg (+), already on antiviral pre-pregnancy	Continue TDF (or switch to TDF if on entecavir or adefovir); do not discontinue abruptly	HBV vaccine dose 1 + HBIG within 12 hours of birth	Permitted

Maternal antiviral therapy is the primary exam-tested intervention. Current guidelines recommend initiating tenofovir disoproxil fumarate (TDF) 300 mg orally once daily beginning at 28 to 32 weeks of gestation in women with HBV DNA levels exceeding 200,000 IU/mL. The goal is to reduce viral load before delivery, thereby decreasing the risk of immunoprophylaxis failure in the neonate. TDF is the preferred agent because of its Pregnancy Category B safety profile, high barrier to resistance, and extensive safety data in pregnancy (largely from HIV treatment cohorts). Tenofovir alafenamide (TAF) has less pregnancy safety data and is generally not the first-line choice, though emerging data suggest comparable safety.

Entecavir is not recommended in pregnancy (Category C, limited data, embryotoxic in animal studies). If a woman is on entecavir pre-conception, she should be switched to TDF before or early in pregnancy.

Regarding timing of discontinuation, if antiviral therapy was started solely for prevention of vertical transmission (not for maternal disease), TDF can be discontinued after delivery or at the time of the first postpartum visit. However, close monitoring of ALT is required in the postpartum period because hepatitis flares can occur after withdrawal of antiviral therapy or after the immune reconstitution that follows delivery. If the mother has underlying chronic active hepatitis requiring long-term treatment, TDF should be continued indefinitely.

Neonatal immunoprophylaxis consists of two components administered within 12 hours of birth: the first dose of the HBV vaccine series (given intramuscularly in the anterolateral thigh) and HBIG 0.5 mL intramuscularly at a separate injection site. The vaccine series is then completed at 1 month and 6 months of age. Post-vaccination serologic testing (HBsAg and Anti-HBs) should be performed at 9 to 12 months of age (or 1 to 2 months after the final vaccine dose) to confirm successful immunization and rule out chronic infection.

Breastfeeding is not contraindicated in HBsAg-positive mothers, provided the neonate has received appropriate immunoprophylaxis. HBV is present in breast milk in small quantities, but the combination of vaccine and HBIG is sufficient to prevent transmission through this route. The only contraindication to breastfeeding would be cracked or bleeding nipples with active viral shedding, though even this is debated and not universally agreed upon.

Mode of delivery: HBV status alone is not an indication for cesarean section. Unlike hepatitis C or HIV (where viral load-driven cesarean recommendations exist), elective cesarean delivery has not been shown to reduce vertical HBV transmission when immunoprophylaxis and maternal antivirals are properly administered. Prolonged rupture of membranes should be avoided when possible, but this is general obstetric management and not an HBV-driven recommendation tested in isolation.

5. Differential Diagnosis and Distractors

Differential Diagnosis	Why It Is Similar	Key Discriminator
Hepatitis C in pregnancy	Also causes chronic viral hepatitis, also screened prenatally, also a concern for vertical transmission	HCV has no vaccine and no immunoglobulin for the neonate; vertical transmission risk is lower (about 5 to 6%); no approved antiviral in pregnancy for HCV prevention of transmission; direct-acting antivirals are not given during pregnancy
Hepatitis A in pregnancy	Can present with acute jaundice and transaminitis in a pregnant patient	HAV does not cause chronic infection and does not carry a vertical transmission risk; diagnosed by Anti-HAV IgM; self-limited illness
Hepatitis E in pregnancy	Acute hepatitis that can be severe in pregnancy, particularly in the third trimester	HEV carries a high maternal mortality rate (up to 20 to 30%) in the third trimester, unlike HBV which is usually well-tolerated; HEV does not cause chronic infection in immunocompetent patients
HELLP syndrome	Elevated transaminases, RUQ pain, can present in late pregnancy	Thrombocytopenia, hemolysis (elevated LDH, schistocytes), and hypertension/proteinuria distinguish this; HBsAg is negative
Intrahepatic cholestasis of pregnancy (ICP)	Pruritus and mildly elevated transaminases in pregnancy	Hallmark is intense pruritus worse on palms and soles with elevated bile acids; no viral serologic markers; ALT elevation is usually mild compared to viral hepatitis
Acute fatty liver of pregnancy (AFLP)	Nausea, vomiting, RUQ pain, markedly abnormal liver function in the third trimester	Distinguished by hypoglycemia, coagulopathy, and low fibrinogen; associated with LCHAD deficiency in the fetus; requires immediate delivery

6. Traps and High-Yield Pearls

The single most common trap on this topic involves confusing serologic markers. Vignettes will present a pregnant woman who is HBsAg (+) and HBeAg (+) and ask for the next best step. Students who do not check the viral load before initiating therapy, or who initiate the wrong antiviral (entecavir instead of tenofovir), will get the question wrong. The tested concept is recognizing that HBeAg positivity alone does not automatically trigger antiviral therapy in pregnancy; it is the quantitative HBV DNA level exceeding 200,000 IU/mL that determines the need for TDF.

Another frequently tested trap involves the timing and components of neonatal immunoprophylaxis. The exam will test whether you know that both vaccine and HBIG must be given within 12 hours, not 24 or 48 hours. Students who select "administer vaccine at routine well-child visit" will miss the critical birth-dose timing. Additionally, HBIG alone without vaccine (or vaccine alone without HBIG) is an incomplete answer for infants born to HBsAg-positive mothers.

A third trap involves breastfeeding. The vignette may present a newly postpartum HBsAg-positive mother and ask whether breastfeeding should be restricted. The correct answer is that breastfeeding is permitted after the neonate has received immunoprophylaxis. Selecting "contraindicated" is a common error driven by the misconception that HBV in breast milk poses a meaningful risk after proper vaccination and HBIG.

Finally, do not recommend cesarean section solely based on HBV status. Unlike certain HIV scenarios, there is no evidence that elective cesarean reduces vertical HBV transmission when appropriate antiviral and immunoprophylaxis measures are in place. The core competency being tested across all these scenarios is your ability to sequence interventions correctly: screen universally with HBsAg, risk-stratify with HBeAg and viral load, treat with TDF when indicated at 28 to 32 weeks, and ensure dual neonatal immunoprophylaxis within 12 hours of birth.

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