Differential Relapse Patterns After Discontinuation of Entecavir vs Tenofovir Disoproxil Fumarate in Chronic Hepatitis B

Background and Aims: Whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differentially affect relapse and outcomes following treatment discontinuation across different patient subpopulations remains unclear. We aimed to compare rates of off-therapy hepatitis B surface antigen (HBsAg) loss, virological and clinical relapse, and retreatment between chronic hepatitis B (CHB) patients who discontinued TDF or ETV therapy. Methods: This study included 1402 virally suppressed CHB patients who stopped either ETV (n = 981) or TDF (n = 421) therapy between 2001 and 2020 from 13 participating centers across North America, Europe, and Asia. All patients were hepatitis B e antigen–negative at treatment discontinuation. Inverse probability of treatment weighting was used to balance the treatment groups. Outcomes were analyzed using survival methods. Results: During a median off-treatment follow-up of 18 months, HBsAg loss occurred in 96 (6.8%) patients overall. Compared with ETV, TDF was associated with a higher rate of HBsAg loss (P = .03); however, the association was no longer significant after statistical adjustment (P = .61). Virological relapse occurred earlier among TDF-treated patients (P < .01); nonetheless, rates became comparable after the first year off therapy (P = .49). TDF was significantly associated with a higher clinical relapse rate than ETV throughout follow-up (P < .01). The development of a virological or clinical relapse did not affect the rate of HBsAg loss. Retreatment rates were not significantly different between the treatment groups. Conclusions: TDF and ETV have differential relapse patterns but are associated with similar rates of HBsAg loss and retreatment following discontinuation. Finite therapy can be considered for CHB patients on either TDF or ETV therapy.