Incidences of Virological and Clinical Relapses After Cessation of Tenofovir Alafenamide, Tenofovir Disoproxil Fumarate, or Entecavir in Patients With HBeAg‐Negative Chronic Hepatitis B

ABSTRACT Background and Aim The relapse pattern following the discontinuation of tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB) remains unclear. This study aimed to compare the 2‐year incidences of virological and clinical relapses among patients who discontinued TAF versus those who discontinued tenofovir disoproxil fumarate (TDF) or entecavir (ETV). Methods This multicenter retrospective study enrolled noncirrhotic hepatitis B e antigen (HBeAg)‐negative CHB patients who discontinued TAF, TDF, or ETV with undetectable HBV DNA at treatment cessation. For patients who switched from ETV or TDF to TAF, a minimum TAF exposure duration of 12 months was required for inclusion in the off‐TAF group. Inverse probability of treatment weighting was employed to adjust for baseline differences. Results A total of 162 patients (off‐TAF: 37, off‐TDF: 87, off‐ETV: 38) were included in the primary analysis. The 2‐year cumulative incidence of virological relapse was significantly higher in the off‐TAF group (85.0%) compared to the off‐TDF group (69.5%, p = 0.024) and the off‐ETV group (51.5%, p = 0.010). Similarly, the 2‐year cumulative incidence of clinical relapse was significantly higher in the off‐TAF group (62.4%) compared to the off‐TDF group (39.0%, p = 0.026) and the off‐ETV group (22.5%, p = 0.024). Consistent results were observed in patients meeting the 2012 APASL stopping criteria. Conclusions HBeAg‐negative patients who discontinue TAF face a higher risk of both virological and clinical relapses compared to those discontinuing TDF or ETV. These findings underscore the need for more intense monitoring in CHB patients after TAF cessation.