Antiviral prophylaxis to prevent hepatitis B reactivation in patients receiving anti–CD20-based chemotherapy and with inactive HBV infection: Systematic review and meta-analysis of randomized controlled trials.

e15034 Background: Patients with history of inactive hepatitis B receiving anti-CD20-based chemotherapy for lymphoma remain at risk for HBV reactivation and reverse seroconversion, which can cause hepatitis and disrupt cancer treatment. We aim to provide randomized evidence on whether routine antiviral prophylaxis is needed in those patients. Methods: We searched PubMed, Embase, Cochrane Library and ClinicalTrials.gov for randomized controlled trials enrolling adults with inactive HBV receiving anti-CD20-based chemotherapy (predominantly rituximab-based; one trial included obinutuzumab) and comparing high-barrier antiviral prophylaxis (entecavir or tenofovir formulations) versus placebo/observation. Inactive HBV was defined as HBsAg-negative and anti-HBc-positive; anti-HBs could be positive or negative. Baseline HBV DNA requirements varied across included trials. Some of them required HBV DNA negativity at enrollment and others permitted low-level detectable HBV DNA. Outcomes were pooled as risk ratios (RR) using a DerSimonian-Laird random-effects model. Primary outcome: HBsAg reverse seroconversion. Secondary outcomes: HBV reactivation, HBV-associated hepatitis, and all-cause mortality. Results: Four RCTs (N = 373) met inclusion. HBsAg reverse seroconversion was not significantly different between the two groups RR 0.42 (95% CI 0.07-2.43; I² = 25.5%). Antiviral prophylaxis reduced the risk of HBV reactivation RR 0.13 (95% CI 0.03-0.57; I² = 0%). There was no difference in HBV-associated hepatitis RR 0.44 (95% CI 0.06-3.09; I² = 0%). All-cause mortality did not differ RR 0.63 (95% CI 0.34-1.16; I² = 0%). Conclusions: High-barrier antiviral prophylaxis in patients receiving anti-CD20-based chemotherapy and have inactive HBV infection reduces HBV reactivation significantly with no significant reduction in reverse seroconversion, HBV-associated hepatitis or all-cause mortality. Trial HBsAg reverse seroconversion HBV reactivation HBV-associated hepatitis All-cause mortality Huang et al, 2013 0/41 vs 4/39 1/41 vs 7/39 0/41 vs 1/39 Not Reported Liu et al, 2018 0/95 vs 2/95 0/95 vs 3/95 0/95 vs 1/95 10/95 vs 16/95 Buti et al, 2017 0/33 vs 1/28 0/33 vs 3/28 0/33 vs 1/28 4/33 vs 5/28 Vakili et al, 2025 2/20 vs 0/22 0/20 vs 0/22 0/20 vs 0/22 0/20 vs 1/22 Total 2/189 vs 7/184 1/189 vs 13/184 0/189 vs 3/184 14/148vs 22/145