EASL and AASLD Guidelines for Hepatitis B Virus Treatment
According to both EASL and AASLD guidelines, high potency nucleos(t)ide analogues (NAs) with high barrier to resistance - entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) - are the recommended first-line treatments for chronic hepatitis B virus infection. 1, 2
Treatment Indications
HBeAg-Positive CHB:
- EASL: Treat if HBV DNA >2000 IU/mL, ALT >ULN, and/or at least moderate liver necroinflammation or fibrosis 1
- AASLD: Treat if HBV DNA ≥20,000 IU/mL and ALT >2× ULN or evidence of significant histological disease 1
HBeAg-Negative CHB:
- EASL: Treat if HBV DNA >2000 IU/mL, ALT >ULN, and/or at least moderate liver necroinflammation or fibrosis 1
- AASLD: Treat if HBV DNA >2000 IU/mL and ALT >2× ULN, or persistent ALT >ULN but <2× ULN with HBV DNA >2000 IU/mL 1
Cirrhosis:
- Both guidelines: Treat all patients with compensated or decompensated cirrhosis with any detectable HBV DNA, regardless of ALT levels 1
First-Line Treatment Options
Nucleos(t)ide Analogues (NAs):
- Entecavir (0.5 mg daily): High potency with >90% virologic response rates and minimal resistance in treatment-naïve patients 2
- Tenofovir disoproxil fumarate (300 mg daily): Comparable efficacy to entecavir with high virologic response rates and minimal resistance 2
- Tenofovir alafenamide (25 mg daily): Similar efficacy to TDF but improved safety profile for renal and bone health 2, 3
Pegylated Interferon:
- May be considered in select patients without cirrhosis due to finite treatment duration and higher rates of HBeAg seroconversion and HBsAg loss compared to NAs 2
Special Populations
Pregnant Women:
- EASL: For pregnant women with high HBV DNA levels (>200,000 IU/mL) or HBsAg levels >4 log10 IU/mL, antiviral prophylaxis with TDF should begin at 24-28 weeks of gestation 1
- AASLD: For pregnant women with HBV DNA >200,000 IU/mL at 28-32 weeks of gestation, TDF is recommended 1
Immunosuppression/Chemotherapy:
- EASL: All HBsAg-positive patients should receive ETV or TDF or TAF as prophylaxis before cytotoxic therapy 1
- AASLD: HBsAg-positive patients should initiate anti-HBV prophylaxis before immunosuppressive therapy 1
Acute Hepatitis B:
- EASL: Patients with severe acute hepatitis B (coagulopathy or protracted course) should be treated with NAs 1
- AASLD: Treatment indicated for patients with acute liver failure or protracted severe course (total bilirubin >3 mg/dL, INR >1.5, encephalopathy, or ascites) 1
HIV Co-infection:
- EASL: HIV-HBV co-infected patients should be treated with a TDF or TAF-based ART regimen 1
- AASLD: Patients already receiving effective ARVT should have treatment changed to include TDF or TAF with emtricitabine or lamivudine 1
Monitoring Recommendations
- HBV DNA levels every 3-6 months
- ALT/AST levels every 3-6 months
- HBeAg/anti-HBe status every 6-12 months
- Renal function every 6-12 months
- Non-invasive fibrosis assessment annually 2
Treatment Efficacy
Treatment outcomes at 48 weeks for HBeAg-positive CHB:
| Agent | HBV DNA <60-80 IU/mL | ALT normalization | HBeAg seroconversion | HBsAg loss |
|---|---|---|---|---|
| PEG-IFN-2a | 14% | 41% | 32% | 3% |
| Entecavir | 67% | 68% | 21% | 2% |
| Tenofovir | 76% | 68% | 21% | 3% |
| [2] |
Important Considerations
- First-generation antivirals (lamivudine, adefovir, telbivudine) should be avoided due to their low potency and high frequency of drug resistance 2
- Patients with family history of HCC or cirrhosis should be considered for treatment even if typical treatment indications are not fulfilled 1
- Patients with extrahepatic manifestations should be considered for treatment regardless of typical liver-related criteria 1
Treatment Endpoints
- Suppression of HBV DNA to undetectable levels is the primary goal of therapy
- HBeAg seroconversion in HBeAg-positive patients
- HBsAg loss, while rare, represents the optimal endpoint of therapy 1
Both EASL and AASLD guidelines emphasize the importance of long-term viral suppression to prevent disease progression, with high-barrier-to-resistance NAs (entecavir, TDF, or TAF) as the cornerstone of treatment for most patients with chronic HBV infection.