What are the key considerations for managing a patient in their 50s with long-standing hepatitis B (HBV) who has achieved viral suppression with negative DNA markers, normal liver fibrosis scan, and normal liver enzymes while on antiviral medication?

Key Surveillance Priorities for Well-Controlled Chronic Hepatitis B

Despite achieving viral suppression with undetectable HBV DNA, normal liver enzymes, and no fibrosis, you must continue lifelong hepatocellular carcinoma (HCC) surveillance and maintain indefinite antiviral therapy—these patients remain at risk for liver cancer even with excellent disease control. 1, 2

Continue Antiviral Therapy Indefinitely

• Do not discontinue nucleos(t)ide analogue therapy unless the patient achieves HBsAg loss (functional cure), which occurs in only a minority of treated patients 3
• Patients with HBeAg-negative chronic hepatitis B require indefinite treatment, as stopping therapy results in 80-90% relapse rates within 1-2 years 3
• Even patients without cirrhosis who have achieved viral suppression should remain on therapy long-term to prevent virologic relapse 3, 2

Mandatory HCC Surveillance Protocol

This is the most critical monitoring requirement that directly impacts mortality:

• Perform liver ultrasound every 6 months regardless of viral suppression status 1, 2
• For patients in their 50s, HCC risk remains elevated due to:
  • Age >40 years (if male) or >50 years (if female) 1, 2
  • Long-standing HBV infection duration 1
  • Prior inflammation/fibrosis exposure even if currently resolved 3
• Consider adding AFP (alpha-fetoprotein) measurement every 6 months, though ultrasound is the primary surveillance tool 1
• HCC can develop even in patients with sustained viral suppression and no cirrhosis—this is a unique feature of HBV-related carcinogenesis 3

Regular Virologic and Biochemical Monitoring

• Check HBV DNA and ALT every 6 months to confirm sustained viral suppression and detect any breakthrough 3, 2
• Monitor for virologic breakthrough (detectable or rising HBV DNA), which may indicate:
  • Medication non-adherence (most common cause with entecavir/tenofovir) 3, 4
  • Rare antiviral resistance 4, 5
• If virologic breakthrough occurs, immediately assess medication adherence before considering resistance testing 3

Assess for Treatment-Related Complications

• Monitor renal function periodically (creatinine, estimated GFR, serum phosphorus) if on tenofovir-based therapy, particularly tenofovir disoproxil fumarate (TDF) 1
• Consider bone density monitoring in patients with additional risk factors for osteoporosis on long-term TDF 1
• Tenofovir alafenamide (TAF) has superior renal and bone safety compared to TDF if switching is needed 1

Watch for Hepatitis Flares

• ALT flares can occur if antiviral therapy is discontinued, even in well-controlled patients 3
• If therapy must be stopped for any reason, monitor ALT monthly for the first 3 months, then every 3 months thereafter 3
• Hepatitis flares in patients with underlying cirrhosis (even if compensated) can lead to decompensation 6

Screen for Immunosuppression Risk

• Before any immunosuppressive therapy or chemotherapy, ensure prophylactic antiviral therapy continues to prevent potentially fatal HBV reactivation 3, 1
• This applies even to patients with undetectable HBV DNA on current therapy 3
• Coordinate with oncology or rheumatology teams if such treatments are planned 3

Common Pitfalls to Avoid

• Never discontinue antiviral therapy based solely on sustained viral suppression—only HBsAg loss justifies stopping treatment 3, 2
• Do not reduce HCC surveillance frequency even with excellent disease control—age and infection duration maintain cancer risk 1, 2
• Do not assume virologic breakthrough means resistance—check adherence first, as this is the most common cause with modern antivirals 3, 4
• Do not use lamivudine, adefovir, or telbivudine if switching therapy is needed—these have high resistance rates and inferior efficacy 3, 1, 5

Optimal Antiviral Agents for Long-Term Therapy

If the patient is not already on one of these, consider switching:

• Entecavir 0.5 mg daily, tenofovir disoproxil fumarate 300 mg daily, or tenofovir alafenamide 25 mg daily are preferred for long-term therapy 1, 2, 5
• These agents have high genetic barriers to resistance (<1-1.2% after 5+ years in treatment-naïve patients) 1, 4
• Tenofovir shows no documented resistance even after prolonged use 1