Higher Relapse Rate in HBeAg-negative Patients After Cessation of Tenofovir Alafenamide Compared to Entecavir or Tenofovir Disoproxil Fumarate.

Objectives: There is limited information comparing the off-therapy relapse rates of patients discontinued tenofovir alafenamide (TAF) to those stopping entecavir or tenofovir disoproxil fumarate (TDF).

Methods: A total of 805 HBeAg-negative patients without cirrhosis receiving entecavir (n=406), TDF (n=260) or TAF (n=139) were enrolled. Propensity-score (PS) matching method was applied to eliminate the significant differences in clinical characteristics.

Results: The cumulative incidences of virological relapse, clinical relapse and retreatment at 96 weeks were higher in the off-TAF group (89.6%, 70.3% and 59.2%, respectively) than that in the off-entecavir group (65.9%, 42.8% and 28.8%, respectively) or the off-TDF group (73.7%, 49.8% and 35.7%, respectively). The median time to clinical relapse was much earlier for off-TAF patients than for off-entecavir or off-TDF (median: 14, 57 and 26 weeks, respectively) and these findings persisted even after PS matching. Multivariate analysis indicated that TAF therapy was an independent risk factor for virological relapse, clinical relapse and retreatment when compared to entecavir or TDF. End-of-treatment HBsAg levels were predictive of virological, but not clinical, relapse, in the off-TAF group, although this group had a lower rate of severe hepatitis upon clinical relapse than the off-TDF group. Finally, there was no significant difference in the hepatic decompensation rate among the entecavir, TDF and TAF groups.

Conclusions: There is an earlier and higher HBV relapse rate in patients who discontinue TAF therapy than in comparable patients discontinuing entecavir or TDF therapy. Close monitoring is necessary after TAF withdrawal, particularly in the first 3 months.