Guidelines 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 specific consolidation periods depending on HBeAg status and presence of cirrhosis. 1
Primary Stopping Criteria by Patient Category
HBeAg-Positive Chronic Hepatitis B
Preferred stopping criterion:
- HBsAg loss (with or without anti-HBs seroconversion) 1
Alternative stopping criterion (less preferred):
- HBeAg loss/seroconversion PLUS undetectable HBV DNA PLUS 12 months of consolidation therapy after achieving these endpoints 1
HBeAg-Negative Chronic Hepatitis B
Preferred stopping criterion:
- HBsAg loss (with or without seroconversion) 1
Alternative stopping criterion (controversial and not universally recommended):
- May be considered after ≥3 years of virological suppression with undetectable HBV DNA on at least 3 separate occasions, each 6 months apart 1
- However, the AASLD recommends indefinite treatment for HBeAg-negative patients, as relapse rates can reach 70% within 36 months after discontinuation 1, 2
Compensated Cirrhosis
- Long-term (potentially lifelong) treatment is recommended 1, 3
- Discontinuation may only be considered after HBsAg loss 1
- The risk of hepatic decompensation, jaundice, and death has been documented after treatment discontinuation in cirrhotic patients 2
Decompensated Cirrhosis
- Indefinite (lifelong) treatment is mandatory 1, 3
- Treatment should never be stopped unless HBsAg loss and anti-HBs seroconversion is achieved and maintained for 6-12 months 3
Critical Warnings About Stopping Tenofovir
High relapse risk:
- Virological relapse is well-documented after stopping nucleos(t)ide analogues, particularly in HBeAg-negative patients 2
- Stopping treatment before achieving HBsAg loss leads to loss of treatment benefits and risks clinical exacerbations 1
Serious complications in cirrhosis:
- Hepatic decompensation, jaundice, and death have been reported in cirrhotic patients who discontinued treatment 2
- The ultimate goal of antiviral therapy is prevention of liver disease progression and HCC development, which requires sustained viral suppression 1
When to Switch (Not Stop) Tenofovir
Switch from TDF to alternative agents if:
- TDF-associated renal dysfunction develops (discontinue TDF immediately and switch to entecavir or TAF) 1, 4
- TDF-associated bone disease or Fanconi syndrome occurs (switch to entecavir or TAF) 1, 4
- Patient has risk factors: age >60 years, preexisting renal disease, bone disease, concurrent ritonavir-boosted protease inhibitors, or previous adefovir exposure 1, 4
Alternative agents after TDF discontinuation:
- Entecavir (minimal renal toxicity, effective for HBV) 4
- Tenofovir alafenamide (TAF) (similar efficacy with reduced renal and bone toxicity, but avoid if creatinine clearance <30 mL/min) 4
- Besifovir (where available, based on previous treatment history) 4
Monitoring After Any Treatment Discontinuation
If treatment is stopped (only after HBsAg loss):
- Monitor liver function tests every 1-3 months initially 1
- Measure HBV DNA by real-time PCR every 2-6 months 1
- Check HBsAg and anti-HBs every 6-12 months 1
- Monitor ALT monthly for first 3 months, then every 3 months in the first year 1
Common Pitfalls to Avoid
- Never stop tenofovir in decompensated cirrhosis unless HBsAg loss is achieved and maintained 3, 2
- Do not stop based solely on undetectable HBV DNA without achieving HBsAg loss, as this leads to high relapse rates 1, 2
- Do not confuse switching medications (for safety) with stopping treatment entirely - most patients require lifelong antiviral therapy 1
- Cost is not a valid reason to stop treatment in most patients, as there is no robust evidence supporting discontinuation 2