What are the differences between the European Association for the Study of the Liver (EASL) 2025 guidelines and the American Association for the Study of Liver Diseases (AASLD) 2018 guidelines for managing liver diseases?

Key Differences Between EASL 2025 and AASLD 2018 Guidelines for Chronic Hepatitis B

The EASL 2025 guidelines represent a significant simplification and liberalization of treatment criteria compared to AASLD 2018, most notably by lowering the ALT threshold for treatment initiation from ≥2× ULN to >1× ULN and emphasizing non-invasive fibrosis assessment over histology. 1

Treatment Initiation Criteria

ALT Thresholds

• AASLD 2018 requires ALT ≥2× ULN (with ULN defined as 35 U/L for males and 25 U/L for females) combined with elevated HBV DNA (>20,000 IU/mL for HBeAg-positive or >2,000 IU/mL for HBeAg-negative patients) to initiate treatment 2
• EASL 2025 simplifies this by recommending treatment for patients with HBV DNA >2,000 IU/mL and ALT >1× ULN, regardless of histology 1
• This represents a major shift that will capture more patients earlier in their disease course, potentially preventing progression to advanced fibrosis 1

Fibrosis-Based Treatment Decisions

• AASLD 2018 considers treatment for patients with ALT <2× ULN only if liver biopsy or non-invasive testing demonstrates significant histologic disease, particularly in those >40 years old 2
• EASL 2025 explicitly recommends treatment for patients with significant fibrosis detected by non-invasive tests, even with normal ALT levels 1
• This reflects the growing evidence that fibrosis progression can occur despite normal transaminases and the improved reliability of non-invasive fibrosis assessment tools 1

First-Line Antiviral Agent Preferences

Tenofovir Formulation Hierarchy

• AASLD 2018 lists pegylated interferon, entecavir, TDF, and TAF as co-equal first-line options, with TAF specifically recommended for patients with or at risk for renal dysfunction or bone disease 2
• EASL 2025 is expected to prioritize TAF over TDF as the preferred first-line nucleos(t)ide analogue due to its superior renal and bone safety profile 1
• This shift reflects accumulating real-world safety data demonstrating TAF's advantages in long-term therapy 1

Treatment Duration and Stopping Rules

Finite Therapy Considerations

• AASLD 2018 recommends indefinite treatment for HBeAg-negative patients or until HBsAg loss, with HBeAg-positive patients treated until HBeAg seroconversion plus 12 months consolidation 2
• EASL 2025 introduces finite therapy considerations, including potential treatment discontinuation after ≥3 years of virological suppression in non-cirrhotic HBeAg-negative patients 1
• This represents a paradigm shift based on emerging data from Asian cohorts showing that carefully selected patients may safely discontinue therapy with appropriate monitoring 1, 3

Discontinuation Outcomes

• Recent systematic reviews supporting EASL 2025 demonstrate that discontinuing antiviral therapy in HBeAg-negative patients with undetectable HBV DNA increases HBsAg loss rates (OR 12.65,95% CI 1.58-101.51) but carries moderate risks of virologic relapse (OR 47.17,95% CI 2.79-797.35) 3
• AASLD 2018 does not address finite therapy strategies in detail 2

Monitoring Strategies

Surveillance Intervals

• AASLD 2018 recommends monitoring HBV DNA every 3 months until undetectable, then every 3-6 months during treatment 2
• EASL 2025 is expected to recommend simplified monitoring intervals to improve adherence, particularly in resource-limited settings 1
• EASL 2025 also emphasizes point-of-care HBV DNA testing and non-invasive fibrosis assessment as monitoring tools 1

Special Populations

Cirrhotic Patients

• Both guidelines agree that all patients with compensated cirrhosis and HBV DNA >2,000 IU/mL require treatment regardless of ALT level 2, 1
• EASL 2025 shows a potential preference for TAF or entecavir in cirrhotic patients with renal dysfunction 1
• AASLD 2018 recommends considering TAF or entecavir in patients with or at risk for renal dysfunction or bone disease but does not specifically prioritize these agents in cirrhosis 2

Immune-Tolerant Phase

• AASLD 2018 does not recommend antiviral therapy for immune-tolerant CHB patients (moderate evidence, strong recommendation) 2
• Recent systematic reviews for the 2025 AASLD update reveal uncertain benefits of treating persons in the immune-tolerant phase, with very low certainty due to heterogeneity and bias 3
• The evidence remains insufficient to support routine treatment of this population in either guideline framework 3

Methodological Differences

Guideline Development Process

• AASLD 2018 was developed as an updated guidance article by expert consensus, complementing the 2016 AASLD guideline which used formal GRADE methodology 2
• EASL 2025 is expected to follow GRADE-adapted methodology similar to their previous guidelines 2, 4
• The AASLD 2018 guidance did not use formal systematic review or GRADE approach for its additional recommendations 2

Common Pitfalls and Clinical Implications

Risk of Premature Treatment Discontinuation

• Clinicians following EASL 2025 finite therapy recommendations must carefully select appropriate candidates and implement rigorous post-treatment monitoring to detect virologic relapse and clinical flares 3
• The moderate risk of virologic relapse (OR 47.17) means this strategy requires shared decision-making and close follow-up 3

ALT Threshold Confusion

• The lower ALT threshold in EASL 2025 (>1× ULN vs ≥2× ULN in AASLD 2018) will identify more treatment candidates 1, 2
• Clinicians must recognize that both guidelines use different ULN definitions (AASLD: 35/25 U/L for males/females; traditional labs often use higher values) 2

Non-Invasive Testing Integration

• EASL 2025's emphasis on non-invasive fibrosis assessment for treatment decisions requires familiarity with elastography thresholds and their limitations 1
• AASLD 2018 mentions non-invasive testing but does not integrate it as prominently into treatment algorithms 2