Does a patient with hepatitis B (HBV) core antibody (cAb) positive, surface antigen (sAg) negative, and hepatitis B e-antigen (HBeAg) negative, consistent with past infection but with unknown history, ever need hepatitis B virus (HBV) deoxyribonucleic acid (DNA) testing?

HBV DNA Testing for Patients with Past Hepatitis B Infection

HBV DNA testing is recommended for patients with serologic evidence of past HBV infection (HBsAg negative, HBcAb positive, HBeAg negative) who will undergo immunosuppressive therapy, but is generally not necessary for patients without planned immunosuppression.

Understanding the Serologic Profile

The serologic pattern described (HBsAg negative, HBcAb positive, HBeAg negative) is consistent with:

• Past or resolved HBV infection, where the virus has been cleared from serum but may persist as covalently closed circular DNA (cccDNA) in hepatocytes 1
• This pattern indicates the patient has been exposed to HBV in the past and has developed an immune response 1
• The absence of HBsAg suggests the patient is not actively infected, though occult HBV infection (OBI) remains a possibility 2

Risk Assessment for HBV Reactivation

The need for HBV DNA testing depends primarily on future immunosuppression risk:

• Patients with this serologic profile are at risk for HBV reactivation if they undergo immunosuppressive therapy 1
• The risk of reactivation varies from 3-45% in HBcAb-positive patients receiving immunosuppression 1
• Risk factors that warrant HBV DNA testing include:
  • Planned chemotherapy or immunosuppressive therapy 1
  • Anti-CD20 therapy (rituximab) or stem cell transplantation (highest risk) 1
  • Other immunosuppressive regimens including high-dose corticosteroids, tyrosine kinase inhibitors, and anti-CD52 monoclonal antibodies 1

Recommendations Based on Clinical Scenario

For patients NOT undergoing immunosuppression:

• Routine HBV DNA testing is generally not necessary for patients with past infection who are not undergoing immunosuppression 1
• These patients typically have undetectable HBV DNA in serum and are considered to have resolved infection 1

For patients planning to undergo immunosuppression:

• HBV DNA testing is strongly recommended before starting therapy 1
• If HBV DNA is detectable (viremic), these patients should receive antiviral prophylaxis similar to HBsAg-positive patients 1
• The ASCO guidelines recommend HBV DNA testing before anticancer therapy in patients with evidence of HBV infection 1

Clinical Implications of Occult HBV Infection

• Approximately 10% of HBsAg-negative/HBcAb-positive individuals may have detectable HBV DNA, representing occult HBV infection 2
• Standard HBV DNA assays may not be sensitive enough to detect very low levels of viremia in occult infection 3
• Patients with occult HBV infection are at risk for:
  • Reactivation during immunosuppression 1
  • Progression of liver disease in some cases 2
  • Potential transmission through blood donation or organ transplantation 3

Monitoring Recommendations

• For patients with past HBV infection not receiving immunosuppression:

  • No specific monitoring for HBV DNA is recommended 1
  • Normal liver function tests suggest inactive disease 1

• For patients with past HBV infection undergoing immunosuppression:

  • If not receiving antiviral prophylaxis: Monitor HBsAg and ALT every 3 months during anticancer therapy 1
  • If receiving antiviral prophylaxis: Check HBV DNA and ALT at baseline and every 6 months during antiviral therapy 1
  • Continue monitoring for at least 12 months after completing immunosuppressive therapy 1

Common Pitfalls and Caveats

• Anti-HBs positivity (surface antibody) may provide some protection against reactivation, but does not completely eliminate the risk 1
• False-negative HBsAg results can occur in patients with chronic liver disease 1
• HBV DNA levels may fluctuate over time, so a single negative test does not definitively rule out occult infection 4, 5
• HBeAg and HBV DNA are not always correlated; HBeAg-negative patients can still have detectable HBV DNA 5

In summary, while routine HBV DNA testing is not necessary for all patients with past HBV infection, it is essential for risk assessment before immunosuppressive therapy to guide appropriate prophylactic management and prevent potentially life-threatening HBV reactivation.