What are the current treatment recommendations for chronic hepatitis B according to the 2025 guideline?

Current Treatment Recommendations for Chronic Hepatitis B

Based on the most recent 2025 guidelines, entecavir or tenofovir are the preferred first-line agents for chronic hepatitis B due to their high potency and high genetic barrier to resistance. 1, 2

Treatment Indications by Patient Category

HBeAg-Positive Chronic Hepatitis B

• Initiate treatment if ALT >2 times normal OR moderate/severe hepatitis on biopsy 3, 2
• Observe for 3-6 months before starting treatment in compensated liver disease to allow for possible spontaneous HBeAg seroconversion 3, 2
• Do NOT treat patients with persistently normal or minimally elevated ALT (<2 times normal) unless liver biopsy demonstrates moderate/severe inflammation 3, 2
• For children: Consider treatment if ALT remains >2 times normal for longer than 6 months 3

HBeAg-Negative Chronic Hepatitis B

• Treat when HBV DNA ≥10^5 copies/mL AND ALT ≥2 times normal OR moderate/severe hepatitis on biopsy 3, 1
• Long-term treatment is typically required given the need for sustained viral suppression 3

Inactive HBsAg Carriers

• Antiviral treatment is NOT indicated 3

First-Line Treatment Selection

Preferred Agents (2025 Standard)

• Entecavir or tenofovir are the recommended first-line therapies due to superior potency and minimal resistance development 1, 2, 4, 5
• These agents have largely replaced older medications (lamivudine, adefovir) which have higher resistance rates 4, 5

Special Cirrhosis Considerations

• Compensated cirrhosis: Use nucleos(t)ide analogues (entecavir or tenofovir preferred) rather than interferon due to risk of hepatic decompensation from interferon-related hepatitis flares 3, 1, 2
• Decompensated cirrhosis: Use nucleos(t)ide analogues immediately and coordinate with transplant centers 3, 2
• Interferon is absolutely contraindicated in decompensated cirrhosis 3, 2

Treatment Duration

HBeAg-Positive Disease

• Minimum 1 year of treatment 3, 2
• Continue for 3-6 months after confirmed HBeAg seroconversion (confirmed on two occasions at least 2 months apart) to reduce post-treatment relapse 3, 2
• Treatment may be continued indefinitely if HBeAg seroconversion does not occur 3

HBeAg-Negative Disease

• Treatment duration longer than 1 year is required, but optimal duration remains undetermined 3, 2
• Most patients require indefinite therapy given low functional cure rates 4

Management of Treatment Failure

Lamivudine Resistance

• Switch to adefovir (or preferably tenofovir in current practice) if breakthrough infection occurs, especially with worsening liver disease, decompensated cirrhosis, post-transplant recurrence, or need for immunosuppressive therapy 3, 2
• For patients switching from lamivudine to adefovir, overlap therapy for 2-3 months to minimize risk of hepatitis flares 3

Prior Interferon Failure

• Retreat with nucleos(t)ide analogues (entecavir or tenofovir preferred) if treatment criteria are met 3, 2

Special Populations

Pediatric Dosing

• Interferon-α: 6 MU/m² thrice weekly (maximum 10 MU) 3, 2
• Lamivudine: 3 mg/kg/day (maximum 100 mg/day) 3, 2

HIV Co-infection

• Lamivudine dose: 150 mg twice daily with other antiretroviral medications 3, 2
• Monitor for drug interactions with HIV protease inhibitors which can increase tenofovir concentrations 6

Pregnancy

• Tenofovir is preferred during pregnancy (FDA pregnancy category B) 1

Immunosuppressive/Chemotherapy Recipients

• Screen all high-risk patients for HBsAg before initiating chemotherapy or immunosuppressive therapy 3
• Initiate prophylactic lamivudine (or preferably entecavir/tenofovir in current practice) at onset of therapy and continue for 6 months after completion 3

Critical Monitoring Requirements

During Treatment

• Monitor HBV DNA levels to assess virological response 1, 2
• Regular liver function tests (ALT, bilirubin, INR) 1
• If using adefovir: Check BUN and creatinine every 1-3 months due to nephrotoxicity risk 3, 2
• Tenofovir: Monitor for renal toxicity, especially when coadministered with HIV protease inhibitors or other nephrotoxic agents 6

After Treatment

• Monitor for HBsAg clearance and anti-HBs seroconversion 1
• Continue liver function monitoring until complete normalization 1

Common Pitfalls and How to Avoid Them

Distinguishing Acute vs. Chronic Disease

• Always differentiate true acute hepatitis B from reactivation of chronic infection, as treatment approaches differ significantly 1
• Acute hepatitis B typically does NOT require treatment (>95% spontaneous recovery), whereas chronic disease often requires long-term therapy 1

Resistance vs. Non-adherence

• Virological breakthrough is more commonly due to medication non-adherence than true resistance when using high-barrier agents like entecavir or tenofovir 1
• Assess adherence before assuming resistance 1

Premature Treatment Discontinuation

• Do not stop treatment prematurely in HBeAg-positive patients—continue for 3-6 months after confirmed seroconversion 3, 2
• Most HBeAg-negative patients require indefinite therapy given high relapse rates 3, 4

Drug Interactions

• Avoid combining tenofovir with adefovir in hepatitis B treatment 6
• Exercise caution when combining tenofovir with nephrotoxic drugs (aminoglycosides, NSAIDs, cidofovir) 6
• Monitor closely when tenofovir is used with HIV protease inhibitors due to increased tenofovir exposure 6