What are the latest Hepatitis B treatment guidelines recommended by the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL)?

Latest Hepatitis B Treatment Guidelines

The most recent major hepatitis B treatment guidelines are: WHO (2024), AASLD (2018 Guidance Update), and EASL (2017), with AASLD providing the most current comprehensive recommendations for clinical practice. 1

Guideline Publication Years and Status

AASLD (American Association for the Study of Liver Diseases)

• Most recent: 2018 Guidance Update published in Hepatology 1
• This updated the 2016 full guidelines with new evidence-based recommendations 1
• The 2018 guidance specifically added tenofovir alafenamide (TAF) as a preferred first-line agent and refined ALT thresholds for treatment decisions 1

EASL (European Association for the Study of the Liver)

• Most recent: 2017 Clinical Practice Guidelines published in Journal of Hepatology 1
• These guidelines emphasize HBV DNA ≥2,000 IU/mL with elevated ALT and/or moderate histological lesions as treatment thresholds 1
• EASL uniquely recommends considering treatment in HBeAg-positive patients over age 30 regardless of ALT if other risk factors are present 1

WHO (World Health Organization)

• First specific HBV guidelines released in 2015, with updates in subsequent years 1
• WHO guidelines are designed with global applicability, including resource-limited settings 1
• They recommend APRI score at cutoff of 2 for cirrhosis assessment in resource-limited areas 1

Key Differences Between Guidelines

Treatment Initiation Criteria

• AASLD 2018: Defines immune-active CHB as ALT ≥2× ULN with HBV DNA >2,000 IU/mL (HBeAg-negative) or >20,000 IU/mL (HBeAg-positive) 1
• AASLD 2018 refined ALT upper limits of normal to 35 U/L for males and 25 U/L for females, which is more stringent than traditional laboratory values 1
• EASL 2017: Similar thresholds but adds age >30 years as a treatment consideration even with normal ALT in HBeAg-positive patients 1

Preferred First-Line Agents

• Both AASLD and EASL agree: Entecavir, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are preferred nucleos(t)ide analogues due to high potency and high genetic barrier to resistance 1, 2
• AASLD 2018 specifically added: TAF as a preferred option, particularly for patients with or at risk for renal dysfunction or bone disease 1
• Pegylated interferon remains an option in both guidelines for selected patients, particularly younger patients planning finite treatment duration 1

Special Populations

Pregnancy and Prevention of Mother-to-Child Transmission:

• AASLD 2018: Recommends TDF for pregnant women with HBV DNA >200,000 IU/mL beginning at 24-32 weeks gestation, stopping 2-12 weeks postpartum 1
• EASL 2017: Similar recommendations with TDF as preferred agent at 24-28 weeks gestation 1
• Both guidelines agree breastfeeding is not contraindicated on TDF 1

Cirrhosis:

• All guidelines agree: Any patient with cirrhosis and detectable HBV DNA should receive treatment regardless of ALT level 1, 2
• AASLD and EASL: Recommend lifelong treatment for cirrhotic patients, with discontinuation only considered after HBsAg loss 3, 2

Immunosuppression/Chemotherapy:

• AASLD 2018: All HBsAg-positive patients should receive prophylactic antiviral therapy before immunosuppression 1
• EASL 2017: Recommends nucleos(t)ide analogues with or without HBIg depending on patient factors 1
• High-risk treatments (>10% reactivation risk) include rituximab, high-dose corticosteroids, and anthracyclines 1

Treatment Duration and Stopping Rules

• AASLD 2018: Generally recommends indefinite treatment, with stopping only after HBsAg loss 3, 2
• For HBeAg-positive patients: Can consider stopping after HBeAg seroconversion plus 6-12 months consolidation, though relapse rates are significant 3
• For HBeAg-negative patients: Indefinite treatment recommended due to high relapse rates 3
• Cirrhotic patients: Should never stop treatment unless HBsAg loss achieved and maintained for 6-12 months 3

Common Pitfalls to Avoid

• Do not use lamivudine, telbivudine, or adefovir as first-line therapy due to high resistance rates 1, 4, 5
• Do not stop monitoring after starting treatment: HBV DNA should be checked every 3-6 months, ALT every 3-6 months, and HBsAg every 6-12 months 1, 3
• Do not overlook renal function monitoring in patients on TDF or adefovir, particularly those with pre-existing risk factors 1, 6
• Do not delay treatment in cirrhotic patients with any detectable HBV DNA, regardless of ALT level 1, 2