Hepatitis B Guidelines- AASLD 2025

The 2025 AASLD/IDSA Practice Guideline on the treatment of chronic hepatitis B was released on November 4, 2025. It includes significant updates compared to the previous guidelines from 2018. Below is a detailed summary of the changes:

1. Pregnancy — Antiviral Prophylaxis to Prevent Mother-to-Child Transmission (MTCT):

• 2018 Guidelines: Suggested initiating antiviral therapy during the third trimester for pregnant women with HBV DNA levels >200,000 IU/mL. Tenofovir disoproxil fumarate (TDF) was the preferred antiviral. Prophylaxis could be stopped at delivery or up to 4 weeks postpartum.
• 2025 Guidelines:
• Strong recommendation to start TDF (preferred) or tenofovir alafenamide (TAF) for women with HBV DNA >200,000 IU/mL.
• Optimal initiation of antiviral therapy is at gestational week 28 (third trimester).
• TAF is now acknowledged as an option, with accumulating safety data supporting its use.
• Earlier initiation (week 16) may be considered in cases where infant hepatitis B immunoglobulin (HBIG) is unavailable or if invasive procedures (e.g., amniocentesis) are anticipated.
• Prophylaxis can be stopped at delivery if there is no ongoing maternal indication, with detailed monitoring recommended after discontinuation.

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2. Drugs Preferred in Pregnancy:

• 2018 Guidelines: TDF was preferred. Lamivudine and telbivudine were shown to reduce MTCT historically but were not preferred. TAF had limited data for pregnancy at the time.
• 2025 Guidelines: TDF remains the preferred antiviral, but TAF is now specifically acknowledged as a viable option due to reviewed safety data. Entecavir is not recommended for use during pregnancy due to insufficient safety data.

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3. Timing of Prophylaxis (Earlier Initiation / Special Circumstances):

• 2018 Guidelines: Antiviral therapy was generally recommended during the third trimester for pregnant women with high viral loads, and postpartum monitoring was advised.
• 2025 Guidelines:
• Week-28 initiation remains optimal for prophylaxis.
• Earlier initiation (week 16) is suggested to control viremia when infant HBIG is not available, based on new randomized controlled trial (RCT) evidence.
• Earlier initiation is also recommended if invasive procedures like amniocentesis are anticipated.

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4. High-Risk Transmission (HBsAg+ Persons in Settings with Risk of Infecting Others):

• 2018 Guidelines: Focused on counseling, vaccination of close contacts, reducing exposure, and considering antiviral therapy for prevention in pregnancy or other high-risk situations.
• 2025 Guidelines:
• For viremic individuals who do not meet disease-specific treatment criteria but are in high-risk transmission scenarios (e.g., immunocompromised contacts, household contacts), shared decision-making about antiviral therapy is recommended (conditional, very low certainty).
• Expanded considerations for implementation include vaccination status and the health of close contacts.

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5. Immune-Tolerant Phase (HBeAg+, Very High HBV DNA, Normal ALT):

• 2018 Guidelines: Treatment was generally not recommended for true immune-tolerant adults. Treatment was reserved for immune-active disease. Monitoring was advised for children/adolescents until they transitioned out of this phase.
• 2025 Guidelines:
• Antiviral therapy is suggested for immune-tolerant individuals >40 years old or those with significant inflammation (≥G2) or fibrosis (≥F2).
• For individuals <40 years old without fibrosis or inflammation, shared decision-making and periodic monitoring are recommended.
• The new guidelines provide clearer thresholds for age, fibrosis, and inflammation to guide treatment decisions.

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6. Indeterminate Phase (HBeAg-Negative, Non-Cirrhotic with Intermediate Labs):

• 2018 Guidelines: Recommended individualized decisions for treatment. Monitoring and treatment were advised when immune-active criteria were met.
• 2025 Guidelines:
• Shared decision-making is explicitly recommended for these HBeAg-negative, indeterminate patients.
• Reassessment is emphasized at each visit if treatment is deferred (conditional recommendation, very low certainty).

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Key Takeaways:

• The 2025 guidelines provide more specific recommendations based on new evidence, particularly regarding pregnancy and high-risk transmission scenarios.
• Tenofovir alafenamide (TAF) is now acknowledged as a safe option during pregnancy, alongside TDF.
• Earlier initiation of prophylaxis is recommended in certain circumstances, such as lack of infant HBIG availability or invasive procedures during pregnancy.
• Clearer criteria for treatment initiation in immune-tolerant and indeterminate phases are outlined, emphasizing shared decision-making and periodic monitoring.

These updates reflect a more nuanced and evidence-based approach to managing chronic hepatitis B, particularly in special populations and settings with higher transmission risks.