When can a patient with chronic hepatitis B discontinue Viread (tenofovir disoproxil fumarate) therapy?

When to Discontinue Viread (Tenofovir Disoproxil Fumarate) for Chronic Hepatitis B

Viread can be discontinued after confirmed HBsAg loss, with or without anti-HBs seroconversion, which represents the safest and most definitive endpoint for stopping therapy. 1

Primary Discontinuation Criteria

HBsAg Loss (All Patients)

• Treatment discontinuation should occur after confirmed HBsAg clearance, regardless of HBeAg status. 1
• This is the only universally accepted stopping point across all major guidelines and represents the safest endpoint. 1
• Continue monitoring for at least several months after discontinuation, as severe acute exacerbations of hepatitis have been reported. 2

Conditional Discontinuation Criteria (Selected Patients Only)

HBeAg-Positive Patients Without Cirrhosis

Discontinuation may be considered in non-cirrhotic HBeAg-positive patients who achieve:

• Stable HBeAg seroconversion (loss of HBeAg with appearance of anti-HBe) 1
• Undetectable HBV DNA on three separate occasions 6 months apart 1
• Plus at least 12 months of additional consolidation therapy after HBeAg seroconversion 1

Critical caveat: Relapse rates are high (40-90%) even after HBeAg seroconversion with nucleos(t)ide analogs. 1 Close monitoring is mandatory. 1

HBeAg-Negative Patients Without Cirrhosis

Discontinuation may be considered in highly selected non-cirrhotic HBeAg-negative patients who have:

• Achieved long-term virological suppression (≥3 years of undetectable HBV DNA) 1
• Only if close post-treatment monitoring can be guaranteed 1

Critical caveat: Relapse rates are particularly high in HBeAg-negative patients, with up to 70% experiencing virological relapse within 36 months after discontinuation. 3 The optimal duration of on-therapy virological remission before safe discontinuation remains unclear. 1

Absolute Contraindications to Discontinuation

Patients with Cirrhosis

• Treatment discontinuation is NOT recommended in patients with cirrhosis (compensated or decompensated) due to risk of hepatic decompensation and death. 1
• Life-long treatment is required for decompensated cirrhosis. 1
• For compensated cirrhosis, discontinuation may only be considered after HBsAg loss. 1
• Hepatic decompensation, jaundice, and death have been documented in cirrhotic patients after treatment discontinuation. 3

Patients Requiring Immunosuppression

• Patients on or planning immunosuppressive therapy or chemotherapy should continue antiviral therapy throughout treatment and for 6 months afterward. 1
• Drugs with anti-HBV activity should not be discontinued without substituting another active agent. 1

Mandatory Post-Discontinuation Monitoring

First Year After Stopping Treatment

Intensive monitoring is required:

• Liver function tests and HBV DNA by real-time PCR every 1-3 months 1
• HBeAg and anti-HBe testing every 3-6 months 1
• For patients with cirrhosis who stop therapy: monthly monitoring for the first 6 months, then every 3 months 1

Beyond First Year

• Continue monitoring liver function and HBV DNA every 3-6 months to detect viral relapse 1
• Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months. 2

Retreatment Criteria

• If appropriate, resumption of anti-hepatitis B therapy may be warranted if virological relapse or hepatitis flare occurs. 2
• Monitor for ALT flares (ALT >100 U/mL and 3 times baseline), recurrent viremia, and clinical decompensation. 1

Common Pitfalls to Avoid

• Never discontinue therapy in cirrhotic patients unless HBsAg loss is achieved, as life-threatening decompensation can occur. 1, 3
• Do not assume that HBeAg seroconversion alone is sufficient for safe discontinuation—consolidation therapy of at least 12 months is required. 1
• Avoid discontinuation in HBeAg-negative patients unless they have achieved ≥3 years of virological suppression and can be monitored closely. 1
• Never stop monitoring after discontinuation—severe acute exacerbations can occur months after stopping therapy. 2
• The optimal duration of treatment is unknown for chronic hepatitis B, and most patients require long-term or indefinite therapy. 2

Practical Algorithm

1. Check HBsAg status: If HBsAg loss confirmed → discontinue with close monitoring 1

2. If HBsAg still positive, assess cirrhosis status:

   • Cirrhosis present → continue indefinitely 1
   • No cirrhosis → proceed to step 3

3. Assess HBeAg status:

   • HBeAg-positive: Discontinue only if HBeAg seroconversion achieved + undetectable HBV DNA + ≥12 months consolidation 1
   • HBeAg-negative: Discontinue only if ≥3 years undetectable HBV DNA + close monitoring guaranteed 1

4. Ensure monitoring capacity: Only discontinue if intensive post-treatment monitoring is feasible 1