What should be done for a patient who stopped taking Tenofovir (Tenofovir disoproxil fumarate) last March for hepatitis B treatment?

Immediate Assessment and Monitoring Required

A patient who stopped tenofovir last March (approximately 9-10 months ago) for hepatitis B requires urgent evaluation for HBV reactivation, as virological relapse occurs in up to 70% of patients within 36 months of discontinuation, with potentially fatal hepatic decompensation reported even in non-cirrhotic patients. 1, 2

Critical Initial Evaluation

Perform the following tests immediately:

• HBV DNA viral load - to assess for virological reactivation 3, 4
• Liver function tests (ALT, AST) - to detect hepatic flare 4, 2
• HBsAg and anti-HBs status - to determine if HBsAg loss occurred (the only acceptable reason for stopping) 5, 4
• HBeAg/anti-HBe status - to assess disease phase 3
• Assessment for cirrhosis - as cirrhotic patients face highest risk of decompensation 5, 4

Risk Stratification Based on Current Status

If HBsAg is Still Positive (Most Likely Scenario)

Tenofovir should be restarted immediately, as stopping antiviral therapy without achieving HBsAg loss violates all major guideline recommendations and places the patient at substantial risk. 5, 4, 1

• The AASLD recommends that tenofovir should generally not be stopped in most patients with chronic hepatitis B, and discontinuation is only recommended after achieving HBsAg loss 4
• Fatal hepatitis B reactivation with liver decompensation and death has been documented after stopping nucleoside analogues, even in patients without prior cirrhosis 2
• Relapse rates reach 70% at 36 months post-discontinuation, particularly in HBeAg-negative patients 1

If HBsAg Loss Was Achieved (Rare)

If the patient achieved HBsAg loss before stopping (the only acceptable stopping criterion), continue monitoring without restarting therapy:

• Liver function tests every 1-3 months for the first year 5, 4
• HBV DNA measurement every 2-6 months 4
• HBsAg and anti-HBs checks every 6-12 months to detect reversion 5, 4

Special Considerations by Patient Category

If Patient Has Cirrhosis

Restart tenofovir immediately and continue indefinitely (lifelong). 5, 4

• For compensated cirrhosis, long-term (potentially lifelong) treatment is recommended 5, 4
• For decompensated cirrhosis, indefinite treatment is mandatory and should never be stopped unless HBsAg loss and anti-HBs seroconversion is achieved and maintained for 6-12 months 5, 4
• Hepatic decompensation, jaundice, and death have been specifically described in cirrhotic patients after treatment discontinuation 1

If Patient Was on Immunosuppression

Restart tenofovir immediately and continue for at least 12 months after cessation of immunosuppressive therapy. 5

• Antiviral prophylaxis should be continued for minimum 12 months following anticancer therapy or immunosuppression 5
• For B-cell depleting agents (rituximab, etc.), continue for at least 18 months after therapy completion 5
• HBV reactivation has been observed as late as 6-12 months after cessation of chemotherapy 5

Treatment Reinitiation Protocol

First-line therapy: Restart tenofovir disoproxil fumarate 300 mg daily (or tenofovir alafenamide if renal/bone concerns exist). 3, 4

Alternative if tenofovir contraindicated:

• Entecavir 0.5 mg daily (or 1 mg daily if lamivudine-resistant) 3, 4

Avoid lamivudine due to high resistance risk. 5, 3

Monitoring After Treatment Reinitiation

• HBV DNA every 3 months until undetectable, then every 6 months 3
• Liver enzymes (ALT, AST) every 3-6 months 3
• Annual quantitative HBsAg testing to assess for potential HBsAg loss 3
• Renal function monitoring if using tenofovir, especially if concurrent nephrotoxic agents 6

Critical Warning from FDA Label

The FDA label for tenofovir explicitly warns: "Worsening of your Hepatitis B infection. Your hepatitis B Virus (HBV) infection may become worse (flare-up) if you take tenofovir disoproxil fumarate tablets and then stop it." 6

• Do not let tenofovir run out 6
• If stopped, healthcare provider must check health often and do blood tests regularly to check HBV infection 6
• Report any new or unusual symptoms after stopping tenofovir 6

Duration of Retreatment

Plan for long-term (potentially lifelong) treatment, as there is no robust evidence to support treatment discontinuation in most patients. 1

• The optimal duration of treatment is unknown 6
• The relationship between response and long-term prevention of outcomes such as hepatocellular carcinoma is not known 6
• Treatment should only be reconsidered for discontinuation after achieving HBsAg loss with appropriate consolidation period 5, 4