What is the recommended approach to screen for and treat hepatitis B virus infection, including antiviral prophylaxis and monitoring, before starting disease-modifying therapy for myelodysplastic syndrome?

Hepatitis B Screening and Management in Myelodysplastic Syndrome

Universal Screening Before Therapy

All patients with myelodysplastic syndrome should be screened for hepatitis B virus infection before starting any disease-modifying therapy by testing for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and antibody to hepatitis B surface antigen (anti-HBs), but anticancer therapy should not be delayed while awaiting results. 1

• Testing should include all three serologic markers to identify chronic infection (HBsAg-positive), past exposure (anti-HBc-positive), and immunity status (anti-HBs) 1
• If screening results are not available before initiating therapy, start treatment and implement prophylaxis as soon as positive serology is identified 1, 2

Management Based on Serologic Status

For HBsAg-Positive Patients (Chronic HBV Infection)

Initiate antiviral prophylaxis with entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) immediately upon starting any systemic anticancer therapy, regardless of HBV DNA levels. 1, 2

• Entecavir and tenofovir agents are strongly preferred over lamivudine due to their high barrier to resistance 1, 2
• Lamivudine should be avoided because resistance rates reach up to 70% after 5 years of use 2
• Begin prophylaxis at or before the first dose of disease-modifying therapy without waiting for HBV DNA results 1, 2
• Continue antiviral therapy throughout the entire course of MDS treatment and for a minimum of 12 months after completion of all anticancer therapy 1, 2

For HBsAg-Negative, Anti-HBc-Positive Patients (Past HBV Exposure)

Patients with resolved HBV infection receiving high-risk immunosuppressive therapies require antiviral prophylaxis, while those receiving lower-risk regimens can be managed with close monitoring. 1

High-Risk Therapies Requiring Prophylaxis:

• Anti-CD20 monoclonal antibodies (rituximab) 1, 3
• Stem cell transplantation 1
• High-dose corticosteroids 3
• Anthracyclines 3

For these patients:

• Start entecavir, TDF, or TAF prophylaxis immediately 1, 3
• Continue prophylaxis during therapy and for at least 12 months after completion (18 months for rituximab-based regimens) 1, 2

Lower-Risk Therapies Allowing Monitoring:

• Hypomethylating agents (azacitidine, decitabine) used alone 1
• Lenalidomide 1
• Erythropoiesis-stimulating agents 1

For these patients:

• Monitor HBsAg and ALT every 3 months during therapy and for 6 months after completion 1
• Obtain HBV DNA testing if HBsAg becomes positive or ALT becomes elevated 1
• Initiate preemptive antiviral therapy immediately if HBsAg or HBV DNA becomes detectable 1

For Patients with No Evidence of HBV Infection

• No specific HBV-related monitoring or prophylaxis is required 1
• Consider vaccination against hepatitis B if anti-HBs is negative 3

Monitoring During Antiviral Prophylaxis

Check baseline ALT and HBV DNA levels before starting therapy, then monitor ALT and HBV DNA every 6 months during antiviral prophylaxis. 2, 4

• More frequent monitoring (every 1-3 months) is appropriate for patients on monitoring-only strategies without prophylaxis 1
• Coordinate care with a hepatologist or clinician experienced in HBV management for patients with chronic HBV infection 1, 4

Post-Treatment Management

Continue antiviral prophylaxis for at least 12 months after completing all disease-modifying therapy for MDS (minimum 18 months for rituximab-containing regimens). 1, 2

• Monitor ALT levels monthly for the first 3 months after stopping antivirals, then every 3 months thereafter to detect hepatitis flares 1, 4
• Check HBsAg and HBV DNA every 3 months for the first year after stopping antivirals, then every 6 months 4
• Patients with cirrhosis may require indefinite antiviral therapy even after MDS treatment completion 4

Critical Pitfalls to Avoid

• Never delay MDS therapy while awaiting HBV screening results - start treatment and implement prophylaxis retroactively if needed 1, 2
• Do not use lamivudine monotherapy due to high resistance rates; always use entecavir or tenofovir agents 1, 2
• Do not stop monitoring after completing MDS therapy - HBV reactivation can occur late, up to 12 months after immunosuppression ends 1, 4
• Do not assume anti-HBc-positive patients are safe without prophylaxis when receiving high-risk therapies like rituximab, as reactivation risk remains substantial 1, 3