Tenofovir alafenamide for prevention of HBV reactivation in HBsAg-negative, anti-HBc-positive patients undergoing rituximab-based chemotherapy: A multicenter randomized controlled trial

Background and Aims:

Immunosuppression can cause hepatitis B virus (HBV) reactivation, leading to severe outcomes in patients with "resolved" HBV infection. This multicenter, randomized, placebo-controlled trial assessed the efficacy of preemptive antiviral therapy in HBsAg-negative, anti-HBc-positive patients receiving rituximab-based chemotherapy for non-Hodgkin lymphoma (NHL).

Methods:

Patients were randomized 1:1 to tenofovir alafenamide (TAF)/placebo across 3 phases: chemotherapy plus TAF/placebo (phase 1), TAF/placebo post-chemotherapy (phase 2), and follow-up after therapy cessation (phase 3). The primary endpoint was HBsAg reverse seroconversion. HBsAg and ALT were monitored every 3-12 weeks, depending on treatment phase, and HBV DNA was measured post hoc. ClinicalTrials.gov (NCT02186574).

Results:

Among 42 patients (median age 65.2 years, 52.4% male, 52.4% aggressive lymphoma, 73.8% anti-HBs positive), 20 received TAF and 22 received a placebo. Median ALT was 20.0 U/L (IQR: 15.0-28.0) at baseline. Median follow-up was 69.4 weeks (IQR: 63.7-166), with 6.1 weeks (IQR: 4.7-8.3) between visits. During follow-up, 2 patients in the TAF arm, but none receiving placebo, experienced HBsAg reverse seroconversions: occurring in phase 3 at 62.3 weeks from baseline, and in phase 1 at 20.0 weeks from baseline. Neither patient experienced ALT >2x ULN. HBV DNA >1000 IU/mL was observed in 8 instances among 6 patients, 3 in each arm, with no associated hepatitis. Low-level DNA (<1000 IU/mL) was not indicative of reverse seroconversion, DNA increases, or ALT elevations.
 
Conclusions:

The use of preemptive TAF therapy did not reduce the risk of HBsAg reverse seroconversion; however, the findings should be interpreted with caution as the study was underpowered due to slow enrolment leading to early termination. Low-level HBV DNA elevations were not associated with HBV reactivation. Thus, close HBsAg and ALT monitoring are adequate in HBsAg-negative patients undergoing rituximab-based chemotherapy.