When can tenofovir (tenofovir disoproxil fumarate) be safely discontinued in a patient with chronic hepatitis B?

When to Stop Tenofovir in Hepatitis B

Tenofovir should generally not be stopped in most patients with chronic hepatitis B, and discontinuation is only recommended after achieving HBsAg loss, with the critical exception that treatment must never be stopped in patients with cirrhosis unless HBsAg clearance is achieved. 1, 2

Primary Stopping Criteria by Patient Category

HBeAg-Positive Patients Without Cirrhosis

• The preferred stopping criterion is HBsAg loss (with or without anti-HBs seroconversion). 1, 2
• Discontinuation may be conditionally considered in non-cirrhotic HBeAg-positive patients who achieve stable HBeAg seroconversion, undetectable HBV DNA on three separate occasions 6 months apart, and complete at least 12 months of additional consolidation therapy after HBeAg seroconversion. 2, 3
• The AASLD emphasizes that this decision requires careful consideration of risks including virological relapse, hepatic decompensation, liver cancer, and death versus the burden of continued therapy. 3

HBeAg-Negative Patients Without Cirrhosis

• The AASLD recommends indefinite treatment for HBeAg-negative patients due to high relapse rates, with discontinuation only after HBsAg loss. 1, 3
• The EASL suggests 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) and can guarantee close post-treatment monitoring. 2
• Research shows cumulative relapse rates for HBV DNA >2,000 IU/mL were 56%, 70%, and 72% at 3,12, and 18 months after stopping therapy, highlighting the substantial risk. 4

Absolute Contraindications to Discontinuation

Patients with Cirrhosis

• Treatment discontinuation is not recommended in patients with cirrhosis (compensated or decompensated) owing to the potential for decompensation and death. 3, 1
• For compensated cirrhosis, long-term (potentially lifelong) treatment is required, and discontinuation may only be considered after HBsAg loss. 1, 2
• For decompensated cirrhosis, indefinite (lifelong) treatment is mandatory, and treatment should never be stopped unless HBsAg loss and anti-HBs seroconversion is achieved and maintained for 6-12 months. 1, 2
• Research confirms that hepatic decompensation, jaundice, and death have been documented in cirrhotic patients after treatment discontinuation. 5

Mandatory Post-Discontinuation Monitoring Protocol

If treatment is stopped (only after meeting appropriate criteria), intensive monitoring is essential to detect relapse early:

First Year After Discontinuation

• Liver function tests and HBV DNA by real-time PCR every 1-3 months. 2, 3
• HBeAg and anti-HBe testing every 3-6 months. 2
• Monitor for recurrent viremia, ALT flares, seroreversion, and clinical decompensation. 3

Beyond First Year

• Continue monitoring with liver function and HBV DNA checks every 3-6 months to detect viral relapse. 2
• HBsAg and anti-HBs checks every 6-12 months. 1

Special Monitoring for Cirrhotic Patients

• Patients with cirrhosis who stop therapy (only after HBsAg loss) should be monitored even more closely—monthly for the first 6 months, then every 3 months. 3

Critical Pitfalls to Avoid

Never Discontinue in These Situations

• Never discontinue therapy in cirrhotic patients unless HBsAg loss is achieved, as life-threatening decompensation can occur. 2, 3
• Do not stop treatment based on HBeAg seroconversion alone without the required 12-month consolidation period. 2, 3
• Avoid discontinuation in patients who cannot commit to intensive post-treatment monitoring. 2

Common Misconceptions

• HBeAg seroconversion alone is not sufficient for safe discontinuation—consolidation therapy of at least 12 months is required. 2, 3
• Undetectable HBV DNA alone does not justify stopping treatment; the endpoint must be HBsAg loss in most cases. 1, 2
• The FDA label emphasizes that tenofovir should not be discontinued without first informing the physician, as virological relapse is common. 6

Alternative to Discontinuation: Switching Tenofovir

If tenofovir-associated complications develop, switch to alternative agents rather than stopping treatment:

• The EASL recommends switching from tenofovir disoproxil fumarate to entecavir or tenofovir alafenamide if tenofovir-associated renal dysfunction or bone disease occurs. 1, 3
• In cases of suspected TDF-associated renal dysfunction and/or bone disease, TDF should be discontinued and substituted with TAF or entecavir, with consideration for any previously known drug resistance. 3
• Renal safety monitoring with serum creatinine, phosphorus, urine glucose, and urine protein should be assessed before treatment initiation and periodically thereafter (at least annually, more frequently if high risk). 3

Evidence Quality Considerations

The strongest evidence comes from the 2018 AASLD guidelines 3 and 2019 KASL guidelines 3, which consistently emphasize that discontinuation carries substantial risk. Research data confirms high relapse rates, particularly in HBeAg-negative patients, with up to 70% relapsing within 36 months. 5 The prospective DARING-B study 4 provides the most recent high-quality evidence showing that while discontinuation can be safe in carefully selected non-cirrhotic patients, virological relapse remains common (70% at 12 months), though many patients eventually enter an inactive carrier state without requiring retreatment.