What are the 2024 guidelines for treating chronic hepatitis B?

2024 Hepatitis B Management Guidelines

For chronic hepatitis B, initiate treatment with entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) as first-line monotherapy—these are the only recommended options due to their high genetic barrier to resistance and superior viral suppression. 1

First-Line Treatment Options

The landscape has shifted dramatically from older guidelines that recommended lamivudine or adefovir. Current evidence strongly supports only three agents as first-line therapy: 1

• Entecavir 0.5 mg daily (for treatment-naïve patients) 2
• Tenofovir disoproxil fumarate (TDF) 245 mg daily 1
• Tenofovir alafenamide (TAF) 1

These agents demonstrate no resistance after 8 years of TDF treatment and entecavir resistance remaining <1% after 5 years. 1 Lamivudine and telbivudine are explicitly not recommended due to resistance rates reaching 70% at 5 years. 3

Treatment Indications

Immediate Treatment Required (No Biopsy Needed)

Treat immediately without liver biopsy if: 1, 3

• HBV DNA ≥20,000 IU/mL AND ALT ≥2× ULN (upper limit normal) 3
• Any cirrhotic patient with detectable HBV DNA (regardless of ALT level) 1, 3
• Decompensated cirrhosis with any detectable HBV DNA 1

Treatment After Fibrosis Assessment

Consider treatment if: 3

• HBV DNA ≥2,000 IU/mL AND ALT >1× ULN with liver biopsy showing moderate necroinflammation (≥A2) or significant fibrosis (≥F2) 3
• HBV DNA ≥2,000 IU/mL with normal ALT if non-invasive markers show liver stiffness ≥9 kPa (with normal ALT) or ≥12 kPa (with ALT <5× ULN) 3

Special Population: Age-Based Considerations

For HBeAg-positive patients >30 years with persistently normal ALT and high HBV DNA: treatment may be initiated regardless of histological severity, as true immune tolerance may not exist and clonal hepatocyte expansion occurs. 1, 3

Critical Pitfall to Avoid

Do not rely on traditional ALT cutoffs to exclude liver disease. Normal ALT by conventional laboratory criteria does not exclude significant necroinflammation or fibrosis—this is a common error that delays necessary treatment. 1 Use gender-specific thresholds: male <34 IU/mL, female <30 IU/mL. 4

Special Populations Requiring Immediate Treatment

Pregnancy

Tenofovir DF is the only recommended agent during pregnancy. 3 Initiate prophylaxis at 24-32 weeks gestation for women with HBV DNA >200,000 IU/mL to prevent mother-to-child transmission. 1, 3

Decompensated Cirrhosis

Immediate treatment with entecavir or TDF is mandatory, irrespective of HBV replication level. 1 Pegylated interferon is absolutely contraindicated in decompensated disease. 1 Coordinate with transplant centers immediately. 4

Immunosuppression/Chemotherapy

All HBsAg-positive patients require prophylactic antiviral therapy before starting immunosuppressive therapy or chemotherapy. 3 For HBcAb-positive/HBsAg-negative patients, prophylactic therapy is preferred unless high-level anti-HBs is present. 3

HIV-HBV Coinfection

All HIV-HBV coinfected patients must start antiretroviral therapy regardless of CD4 count, with TDF- or TAF-based regimens being mandatory. 1

Treatment Monitoring Protocol

Monitor with this specific schedule: 1, 3

• HBV DNA every 3 months until undetectable, then every 6 months 1, 3
• ALT/AST every 3-6 months 3
• Annual quantitative HBsAg testing to assess for potential functional cure 3
• Renal function monitoring if on tenofovir (creatinine, phosphate) 1

Treatment Duration and Endpoints

Long-term, potentially indefinite treatment is required with nucleos(t)ide analogues. 1, 3 The optimal endpoint is HBsAg loss (functional cure), but this is rarely achieved with current therapies. 1, 3

Stopping therapy may be considered only in HBeAg-positive patients who achieve: 3

• HBeAg seroconversion
• Undetectable HBV DNA
• Completion of at least 12 months of consolidation therapy after seroconversion

Hepatocellular Carcinoma Surveillance

Ultrasound examination every 6 months is mandatory for: 3

• All cirrhotic patients (regardless of treatment status) 1
• Asian men >40 years 3
• Asian women >50 years 3
• Any patient with family history of HCC 3
• Age >40 years with persistent ALT elevation 3

Choosing Between Entecavir and Tenofovir

Both are equally effective for viral suppression (71-76% undetectable HBV DNA at 48 weeks). 5 Key differentiating factors:

• TAF demonstrates less renal tubular dysfunction and bone mineral density loss compared to TDF through 96 weeks 1
• In cirrhotic patients with refractory ascites, entecavir is preferred over TDF due to lower risk of acute kidney injury (TDF increases AKI risk 3.8-fold in this population) 6
• For pregnancy, TDF is the only recommended option 3

Agents to Avoid

Never use as first-line therapy: 4, 3

• Lamivudine (resistance up to 70% at 5 years) 3
• Adefovir (weak antiviral activity, high resistance after 48 weeks) 4
• Telbivudine (high resistance rates) 4

These older agents are mentioned in 2004 guidelines 4 but have been superseded by superior options with dramatically better resistance profiles.