In a chronic hepatitis B patient on tenofovir (300 mg daily) for >6 years with persistently normal liver function tests and HBV DNA <150 IU/mL for >5 years, should antiviral therapy be stopped?

Should Tenofovir Be Stopped in This Patient?

No, tenofovir should not be stopped in this patient. Despite >6 years of treatment with excellent virologic suppression (HBV DNA <150 IU/mL for >5 years) and normal liver function tests, current guidelines universally recommend continuing antiviral therapy indefinitely until HBsAg loss is achieved. 1, 2

Why Stopping Is Not Recommended

The Critical Missing Endpoint: HBsAg Status

• HBsAg loss (with or without anti-HBs seroconversion) is the only universally accepted stopping point for nucleos(t)ide analogue therapy. This represents a "functional cure" and is the sole criterion endorsed by all major hepatology societies (AASLD, EASL, KASL, APASL). 1, 2
• Your question does not mention HBsAg status—if HBsAg remains positive, therapy must continue regardless of how long HBV DNA has been suppressed. 1, 3

High Relapse Risk Without HBsAg Loss

• Stopping tenofovir before HBsAg loss results in virologic relapse in 50-75% of patients, with many experiencing clinical hepatitis flares that can be severe or even life-threatening, particularly in those with underlying cirrhosis or advanced fibrosis. 1
• Even after years of undetectable HBV DNA, the vast majority of patients experience recurrent viremia within months of stopping therapy. 1

HBeAg Status Matters for Risk Stratification

• If this patient is HBeAg-negative (the most common scenario after 6 years of suppressive therapy), the AASLD explicitly recommends lifelong treatment because relapse rates approach 70-75% after discontinuation, even with ≥3 years of sustained suppression. 1, 3
• If this patient was originally HBeAg-positive and achieved HBeAg seroconversion during treatment, stopping remains high-risk: prospective data show that all HBeAg-positive patients who stopped without HBsAg loss experienced virological relapse, and 75% required retreatment. 1

Fibrosis Stage Is a Critical Contraindication to Stopping

• Patients with significant fibrosis (≥F2), compensated cirrhosis, or any degree of decompensated cirrhosis must never stop therapy unless HBsAg loss is documented. 1, 2
• Even with normal liver function tests, underlying fibrosis may be present—transient elastography or liver biopsy should be performed if fibrosis stage is unknown before any consideration of stopping therapy. 1
• For patients with compensated cirrhosis, lifelong therapy is mandatory; for decompensated cirrhosis, indefinite therapy is absolutely required. 4, 1

What the Guidelines Say About Your Specific Scenario

AASLD (Most Conservative, 2018-2021)

• Indefinite treatment is required for HBeAg-negative patients due to high relapse rates and risk of immune-escape mutants. 4, 1
• Treatment may only be stopped after confirmed HBsAg loss, followed by 6-12 months of consolidation therapy. 1, 2

EASL (Conditional Alternative, 2012-2017)

• In highly selected non-cirrhotic HBeAg-negative patients, therapy may be stopped after ≥3 years of sustained virological suppression (undetectable HBV DNA on three separate tests ≥6 months apart). 4, 1
• However, this approach carries a 70-75% relapse rate and demands extremely close post-treatment monitoring with monthly ALT and HBV DNA checks for the first 3 months, then every 3 months. 1
• This option is not routinely advised and should be limited to patients who can guarantee rigorous follow-up. 1

KASL (Korean Guidelines, 2019)

• The optimal treatment duration is not clearly defined for HBeAg-negative patients, but adult guidelines recommend continuing until HBsAg loss. 4
• For HBeAg-positive patients, treatment should continue for at least 1 year after HBeAg seroconversion. 4

Practical Algorithm for This Patient

Step 1: Check HBsAg Status

• If HBsAg is positive → Continue tenofovir indefinitely. 1, 2
• If HBsAg is negative (lost) → Continue for 6-12 months consolidation, then consider stopping with close monitoring. 1, 2

Step 2: Assess Fibrosis Stage (if HBsAg positive and patient insists on stopping)

• Perform transient elastography or FibroScan. 1
• If ≥F2 fibrosis or any cirrhosis → Absolute contraindication to stopping; continue lifelong therapy. 1
• If F0-F1 fibrosis AND patient is HBeAg-negative with ≥3 years undetectable HBV DNA → Stopping may be considered per EASL criteria, but counsel about 70-75% relapse risk. 1

Step 3: If Stopping Is Considered (Against Standard Recommendations)

• Confirm undetectable HBV DNA on three separate tests ≥6 months apart. 1
• Establish intensive post-cessation monitoring:
  • ALT and HBV DNA monthly for 3 months 1
  • Then every 3 months for the first year 1
  • HBsAg and anti-HBs every 6-12 months 1
• Restart tenofovir immediately if HBV DNA rises to ≥2,000 IU/mL with elevated ALT or any sign of hepatic decompensation. 1

Common Pitfalls to Avoid

• Do not assume that normal LFTs and undetectable HBV DNA for 5 years means the patient is "cured"—HBsAg persistence indicates ongoing infection with high relapse risk upon stopping. 1
• Do not stop therapy without knowing the fibrosis stage—even with normal ALT, significant fibrosis may be present and stopping could precipitate decompensation. 1
• Do not discontinue abruptly without establishing a close monitoring plan—hepatitis flares can be severe and life-threatening, especially in older adults or those with unrecognized cirrhosis. 1
• Do not confuse virologic suppression with cure—tenofovir suppresses but does not eradicate HBV; cccDNA persists in hepatocytes and reactivates upon drug withdrawal. 1, 5

Long-Term Safety of Continued Tenofovir

• Tenofovir has an excellent long-term safety profile with no documented resistance through 7-10 years of continuous therapy. 5, 6
• At 7 years, 99.3% of patients maintain viral suppression, and drug-related grade 3/4 adverse events are uncommon (1.0%). 5
• Renal and bone safety: Only 1.7% of patients had serum creatinine elevation ≥0.5 mg/dL above baseline through 7 years, and no significant change in bone mineral density was observed from year 4 to year 7. 5
• For patients with renal concerns or osteoporosis risk, switching to tenofovir alafenamide (TAF) is preferred over stopping therapy entirely. 4

Bottom Line

Continue tenofovir 300 mg daily indefinitely until HBsAg loss is documented. The patient's excellent virologic response and normal liver function are reasons to continue therapy, not to stop it. Stopping before HBsAg loss carries a 50-75% risk of virologic relapse and potential for severe hepatitis flares. 1, 2 If the patient has concerns about long-term therapy, reassure them that tenofovir is safe for decades of use and consider switching to TAF if renal or bone concerns arise. 4, 5