Can You Stay on Entecavir Before HBV DNA Testing Results Are Back?
Yes, patients with a history of HBV infection who are undergoing or about to undergo immunosuppressive therapy or chemotherapy should continue or initiate entecavir immediately without waiting for HBV DNA results. 1
Key Principle: Do Not Delay Treatment
Anticancer therapy and immunosuppressive treatment should not be delayed for HBV screening test results, and antiviral prophylaxis should be initiated as soon as possible before or, at the latest, simultaneously with the onset of immunosuppressive therapy. 1
The American Society of Clinical Oncology (ASCO) 2020 guidelines explicitly state that while all patients should be tested for HBV (HBsAg, anti-HBc, and anti-HBs) prior to or at the beginning of systemic anticancer therapy, anticancer therapy should not be delayed for these screening test results. 1
When to Start Entecavir Immediately
For HBsAg-Positive Patients:
All HBsAg-positive patients receiving any systemic anticancer therapy should receive antiviral prophylactic therapy immediately, regardless of HBV DNA levels. 1
Entecavir (along with tenofovir disoproxil fumarate [TDF] or tenofovir alafenamide [TAF]) is preferred as a high-barrier-to-resistance agent over lamivudine. 1
For HBsAg-Negative, Anti-HBc-Positive Patients:
Patients receiving high-risk immunosuppression (particularly anti-CD20 antibody therapy like rituximab or undergoing stem-cell transplantation) should initiate prophylaxis immediately without waiting for HBV DNA results. 1
For other HBsAg-negative, anti-HBc-positive patients on moderate-risk regimens, monitoring with HBV DNA every 1-3 months is an alternative strategy, but preemptive therapy should be started immediately upon detection of HBsAg or HBV DNA positivity. 1
Rationale for Not Waiting
Risk of HBV Reactivation:
HBV reactivation during immunosuppressive therapy is associated with significant morbidity and mortality due to hepatitis flares, hepatic decompensation, and fulminant hepatitis. 2, 3
The incidence of fulminant hepatitis from HBV reactivation in resolved HBV infection cases can be higher than that from acute hepatitis B. 3
Timing is Critical:
Prophylaxis should ideally be started 2 to 4 weeks before the initiation of immunosuppressive therapy. 1, 4
When this is not possible, starting simultaneously with immunosuppressive therapy is acceptable and strongly recommended. 1
Monitoring Strategy While on Entecavir
Check ALT and HBV DNA levels at baseline (prior to or at the beginning of anticancer therapy) and every 6 months during antiviral therapy. 1
For patients being monitored without prophylaxis (low-risk scenarios), HBV DNA levels should be obtained every 1-3 months. 1
Duration of Therapy
Continue entecavir during immunosuppressive therapy and for at least 12 months after completion of anticancer therapy. 1
For patients receiving anti-CD20 therapies (rituximab), extend prophylaxis to at least 18 months after the last dose due to prolonged immune recovery. 1
Common Pitfalls to Avoid
Do Not Wait for DNA Results in High-Risk Scenarios:
The most critical error is delaying antiviral prophylaxis while waiting for HBV DNA results in patients about to start high-risk immunosuppression. 1
This delay can result in preventable HBV reactivation, hepatitis flares, and potentially fatal outcomes. 5, 2
Do Not Use Lamivudine:
Avoid lamivudine due to high resistance rates (up to 70% after 5 years). 1, 6
Entecavir, TDF, or TAF should be preferred as first-line agents due to their high barrier to resistance. 1
Do Not Stop Prophylaxis Prematurely:
Severe acute exacerbations of hepatitis have been reported after discontinuing anti-HBV therapy, with reactivation rates ranging from 29.7-91.0%. 7
Close hepatic function monitoring is required for at least several months after stopping therapy. 7
Special Considerations
Rituximab-Containing Regimens:
Rituximab poses particularly high risk for HBV reactivation, even in HBsAg-negative, anti-HBc-positive patients. 1
Prophylactic antiviral therapy is strongly recommended for all patients with any evidence of past HBV exposure receiving rituximab. 1, 7