What are the next steps for a patient who is Hepatitis B surface antigen (HBsAg) reactive and currently on Tenofovir (Tenofovir disoproxil fumarate) 300mg for their annual physical exam?

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Annual Physical Exam Management for HBsAg-Reactive Patient on Tenofovir 300mg

Continue tenofovir 300mg daily and implement structured monitoring with HBV DNA and ALT every 3-6 months, plus annual HCC surveillance if indicated by age and ethnicity. 1

Essential Laboratory Monitoring

Check the following labs at this annual visit:

  • HBV DNA by PCR – This is the single most critical test to confirm viral suppression (target: undetectable or <69 IU/mL) 2, 1
  • ALT/AST – Monitor for hepatic inflammation and treatment response 2, 1
  • Serum creatinine and calculated creatinine clearance – Tenofovir requires renal monitoring every 3 months in at-risk patients, but at minimum every 12 weeks for all patients 2
  • Serum phosphorus – Monitor every 3 months in patients at risk for renal toxicity 2
  • Quantitative HBsAg – Annual testing to assess for potential functional cure (HBsAg loss) 1
  • HBeAg/anti-HBe status (if initially HBeAg-positive) – Check every 6 months to monitor for seroconversion 2

Hepatocellular Carcinoma Surveillance

Initiate or continue ultrasound screening every 6 months if the patient meets any of these criteria: 1

  • Asian men >40 years or Asian women >50 years
  • Any patient with cirrhosis
  • Age >40 years with persistent ALT elevation
  • Family history of HCC

This surveillance continues indefinitely, even with undetectable HBV DNA on treatment 1.

Verify Treatment Adherence and Efficacy

At 8 years of tenofovir treatment, 98-99.6% of patients should have undetectable HBV DNA 2. If viral suppression is not achieved:

  • First, assess medication adherence – Virologic breakthrough with tenofovir is rare and usually indicates nonadherence 2, 3
  • Check for drug-drug interactions (particularly with antidepressants like venlafaxine, paroxetine, or other medications that may affect absorption) 3
  • If adherence is confirmed and breakthrough persists, perform genotypic resistance testing, though no resistance to tenofovir has been documented through 10 years of treatment 2, 4, 5

Coinfection Screening (if not previously done)

Screen for the following if not already completed: 1

  • Anti-HCV antibody
  • Anti-HDV antibody (especially if history of injection drug use)
  • Anti-HIV antibody
  • Anti-HAV antibody – If negative, vaccinate against hepatitis A as coinfection increases mortality 5.6- to 29-fold 1

Ongoing Treatment Considerations

Do not discontinue tenofovir without careful consideration 6. The optimal duration of treatment for chronic hepatitis B is unknown, and the relationship between treatment response and long-term prevention of hepatocellular carcinoma is not established 6. For most patients, indefinite treatment is recommended 1.

Severe acute exacerbations of hepatitis can occur after discontinuation in HBV-infected patients 6. If discontinuation is considered, ALT levels must be monitored at least monthly for the first 3 months, then every 3 months thereafter 2.

Special Circumstances Requiring Immediate Action

If the patient will undergo chemotherapy or immunosuppressive therapy:

  • Continue tenofovir prophylaxis throughout treatment and for at least 12 months after cessation (24 months for rituximab-based regimens) 2, 1
  • Monitor HBV DNA every 6 months during antiviral therapy 2

Preventive Counseling

Reinforce the following at each visit: 6

  • Complete alcohol abstinence – Even limited consumption worsens outcomes 1
  • Avoid sharing needles, razors, or toothbrushes
  • Practice safer sex with barrier protection
  • Do not breastfeed (tenofovir is excreted in breast milk) 6

Common Pitfalls to Avoid

Do not attribute virologic breakthrough solely to resistance – With tenofovir's high barrier to resistance, nonadherence or drug interactions are far more likely causes 2, 3. Do not delay HCC surveillance – Screening should begin immediately for high-risk patients and continue indefinitely regardless of viral suppression 1. Do not monitor less frequently than recommended – The 2015 Clinical Gastroenterology and Hepatology guidelines specify HBV DNA every 12-24 weeks and liver panel every 12 weeks as minimum monitoring 2.

References

Guideline

Management of HBsAg Reactive Patients

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Ten-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B virus infection.

Liver international : official journal of the International Association for the Study of the Liver, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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