What treatment is recommended for a condition requiring antiviral therapy?

Treatment for Chronic Hepatitis B (CHB)

For patients with chronic hepatitis B requiring antiviral therapy, entecavir and tenofovir are the preferred first-line treatments due to their potent antiviral activity and high barrier to resistance. 1

Treatment Indications

Antiviral therapy should be initiated when patients meet the following criteria:

• HBV DNA >2000 IU/ml AND ALT >2× ULN: These patients should be considered for treatment 1
• Compensated cirrhosis with detectable HBV DNA: Treatment may be initiated even if ALT is normal and/or HBV DNA is below 2000 IU/ml 1
• Decompensated cirrhosis: Urgent antiviral treatment is required with rapid and profound viral suppression 1

For patients with HBV DNA >2000 IU/ml but ALT between 1-2× ULN, liver biopsy should be considered, and treatment initiated if moderate/severe necroinflammation or significant fibrosis (≥A2 or ≥F2 by METAVIR scoring) is present 1

First-Line Treatment Options

Preferred Agents

Entecavir and tenofovir are the preferred nucleos(t)ide analogues because they combine potent HBV inhibition with a high barrier to resistance 1. These agents should be used as first-line therapy in both HBeAg-positive and HBeAg-negative patients 1.

Alternative Agents

• Pegylated interferon alpha-2a: Can be considered for patients who prefer finite treatment duration, though it requires subcutaneous injection and has frequent side effects 1
• Adefovir: May be used but is less preferred than entecavir or tenofovir 1
• Lamivudine and telbivudine: Not preferred due to high rates of drug resistance during long-term treatment 1

Treatment Contraindications and Special Considerations

Interferon alpha is absolutely contraindicated in:

• Patients with decompensated HBV-related cirrhosis 1
• Autoimmune disease 1
• Uncontrolled severe depression or psychosis 1

Duration of Therapy

The optimal duration of nucleos(t)ide analogue therapy is generally indefinite unless specific endpoints are achieved 1:

• For HBeAg-positive patients without cirrhosis: Treatment can be withdrawn after HBsAg loss with at least 12 months of post-HBsAg clearance consolidation, OR after at least 2 years of treatment with undetectable HBV DNA documented on 3 separate occasions following HBeAg seroconversion 1
• For patients with cirrhosis: Long-term administration of a potent nucleos(t)ide analogue with high barrier to resistance is the treatment of choice regardless of severity 1

Monitoring During Treatment

For patients on nucleos(t)ide analogue therapy:

• Liver panel every 12 weeks 1
• HBV DNA levels every 12-24 weeks 1
• HBeAg/anti-HBe every 24 weeks if initially HBeAg-positive 1
• Serum creatinine every 12 weeks for patients receiving adefovir or tenofovir 1
• HBsAg every 6-12 months in HBeAg-negative patients with persistently undetectable HBV DNA 1

Management of Drug Resistance

For lamivudine or telbivudine resistance:

• Add adefovir or tenofovir while continuing lamivudine/telbivudine to decrease risk of hepatitis flares and subsequent adefovir resistance 1
• Alternatively, switch to combination tenofovir/emtricitabine (Truvada) 1

For adefovir resistance:

• Add lamivudine or entecavir in patients with no prior nucleos(t)ide analogue exposure 1

For entecavir resistance:

• Switch to or add adefovir or tenofovir 1

Common Pitfalls to Avoid

• Do not delay treatment for 3-6 months in patients with decompensated cirrhosis waiting for spontaneous HBeAg seroconversion—these patients require urgent treatment 1
• Do not use lamivudine or telbivudine as first-line therapy when long-term treatment is anticipated due to high resistance rates 1
• Do not stop lamivudine when adding adefovir for lamivudine resistance, as this increases risk of hepatitis flares 1