What are the differences in treatment recommendations for hepatitis B between the 2025 European Association for the Study of the Liver (EASL) guidelines and the 2018 American Association for the Study of Liver Diseases (AASLD) guidelines?

Key Treatment Differences Between 2025 EASL and 2018 AASLD Hepatitis B Guidelines

The 2025 EASL guidelines are expected to adopt a simplified, public health-oriented approach with broader treatment criteria similar to the 2024 WHO recommendations, while the 2018 AASLD guidelines maintain more restrictive, individualized treatment thresholds requiring ALT ≥2× ULN for most patients.

Treatment Initiation Criteria

2018 AASLD Approach

The AASLD 2018 guidance defines immune-active CHB requiring treatment as:

• HBeAg-positive patients: HBV DNA >20,000 IU/mL with ALT ≥2× ULN 1
• HBeAg-negative patients: HBV DNA >2,000 IU/mL with ALT ≥2× ULN 1
• ALT thresholds: 35 U/L for males and 25 U/L for females as the upper limit of normal 1
• Patients with ALT between 1-2× ULN require liver biopsy or non-invasive testing to demonstrate significant histologic disease (≥A2 inflammation or ≥F2 fibrosis) before treatment 1

Expected 2025 EASL Approach

Based on the 2024 WHO guideline influence, EASL 2025 is anticipated to recommend:

• Simplified treatment criteria: HBV DNA >2,000 IU/mL with ALT >ULN (40 IU/L), regardless of histology 1
• Expanded indications: Treatment for patients with significant fibrosis detected by non-invasive tests (APRI >0.5 or FibroScan >7.0 kPa) even with normal ALT 1
• Age-based considerations: Treatment for patients >30 years with persistent viremia, regardless of ALT elevation 1

Critical difference: The 2025 EASL approach eliminates the requirement for ALT ≥2× ULN and reduces reliance on liver biopsy, making treatment accessible to more patients earlier in disease progression 1.

First-Line Antiviral Agents

2018 AASLD Recommendations

Preferred first-line therapies include:

• Pegylated interferon-alpha (48 weeks for finite therapy) 1
• Entecavir 0.5 mg daily 1
• Tenofovir disoproxil fumarate (TDF) 300 mg daily 1
• Tenofovir alafenamide (TAF) 25 mg daily (added as guidance, preferred in patients with renal dysfunction or bone disease) 1

Expected 2025 EASL Recommendations

Likely to prioritize:

• TAF over TDF as first-line due to superior renal and bone safety profile 2
• Entecavir remains first-line but with caution in lamivudine-experienced patients 1
• De-emphasis of pegylated interferon due to complexity of administration and side effects in resource-limited settings 1

Critical difference: The 2025 EASL guidelines are expected to preferentially recommend TAF over TDF based on accumulating safety data, whereas 2018 AASLD listed both tenofovir formulations equally with TAF as "guidance" rather than primary recommendation 1, 2.

Treatment Duration and Stopping Rules

2018 AASLD Approach

• HBeAg-positive CHB: Continue until HBeAg seroconversion with 12 months consolidation therapy, or indefinitely 1
• HBeAg-negative CHB: Indefinite treatment or until HBsAg loss 1
• Compensated cirrhosis: Long-term treatment recommended 1
• Decompensated cirrhosis: Indefinite treatment regardless of HBV DNA, HBeAg status, or ALT level 1

Expected 2025 EASL Approach

Anticipated to include:

• Finite therapy considerations: Treatment discontinuation after ≥3 years of virological suppression in non-cirrhotic HBeAg-negative patients with close monitoring 1, 3
• HBsAg loss as primary endpoint: Emphasis on HBsAg loss (functional cure) as the ideal treatment goal 1, 3
• Simplified monitoring: Less frequent monitoring requirements to improve feasibility in resource-limited settings 1

Critical difference: The 2025 EASL guidelines are expected to more explicitly endorse finite therapy strategies in carefully selected non-cirrhotic patients, reflecting emerging data from Asian cohorts showing 30% HBsAg loss rates at 5 years post-treatment cessation 3. The 2018 AASLD guidelines recommend indefinite therapy for most HBeAg-negative patients 1.

Special Populations

Cirrhotic Patients

2018 AASLD: All patients with compensated cirrhosis and HBV DNA >2,000 IU/mL require treatment regardless of ALT level; decompensated cirrhosis requires indefinite treatment with entecavir or TDF (TAF not studied in decompensation) 1

Expected 2025 EASL: Similar recommendations but with potential preference for TAF or entecavir in patients with renal dysfunction even in decompensated cirrhosis 1, 2

Pregnant Women

2018 AASLD: TDF preferred for preventing mother-to-child transmission in women with high viremia (>200,000 IU/mL) during third trimester; TAF not recommended due to insufficient pregnancy data 1

Expected 2025 EASL: Likely to maintain TDF as preferred agent but may include updated TAF data if available 1

Renal Impairment

2018 AASLD: TAF or entecavir preferred in patients with creatinine clearance <60 mL/min or bone disease risk; TAF not recommended if creatinine clearance <15 mL/min or on dialysis 1

Expected 2025 EASL: TAF demonstrated safety in moderate-severe renal impairment (eGFR 15-59 mL/min) and ESRD on hemodialysis with 98% achieving HBV DNA <20 IU/mL at 24 weeks 2. Expected stronger recommendation for TAF in renal dysfunction 2.

Monitoring During Treatment

2018 AASLD

• HBV DNA every 3 months until undetectable, then every 3-6 months 1
• ALT monitoring every 3-6 months 1
• HCC surveillance continues regardless of viral suppression 1

Expected 2025 EASL

• Simplified monitoring intervals to improve adherence in resource-limited settings 1
• Greater emphasis on point-of-care HBV DNA testing (GeneXpert) for accessibility 1
• Non-invasive fibrosis assessment (APRI, FibroScan) instead of liver biopsy 1

Common Pitfalls and Caveats

ALT threshold controversy: The 2018 AASLD's requirement for ALT ≥2× ULN may delay treatment in patients with significant fibrosis but modest ALT elevation 1. The expected 2025 EASL approach addresses this by incorporating non-invasive fibrosis testing 1.

Finite therapy risks: While emerging data support treatment discontinuation in select HBeAg-negative patients, hepatitis flares with potential decompensation remain a serious risk requiring close monitoring (ALT every 1-3 months for first year) 3. Retreatment should occur before decompensation but not so early as to prevent immune-mediated HBsAg decline 3.

TAF in decompensated cirrhosis: The 2018 AASLD appropriately notes TAF has not been studied in decompensated cirrhosis 1. However, recent data in renal impairment populations suggest safety, and the expected 2025 EASL guidelines may cautiously expand TAF use in this setting with appropriate monitoring 2.

Resistance concerns: Both guidelines emphasize high genetic barrier agents (entecavir, TDF, TAF) to prevent resistance 1. Lamivudine and telbivudine should be avoided due to high resistance rates 1.