Higher relapse rate after stopping tenofovir alafenamide compared with entecavir; but not tenofovir disoproxil fumarate in HBeAg-positive patients.

BACKGROUND/PURPOSE: This study compares the hepatitis B virus (HBV) relapse rates after discontinuation of entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) therapy in HBeAg-positive patients.

METHODS

This study was a retrospective analysis of a prospectively collected cohort comprising 427 HBeAg-positive patients without cirrhosis who received entecavir (n=200), TDF (n=133), or TAF (n=94) were enrolled. All patients met the Taiwan National Health Insurance stopping criteria for antiviral therapy.

RESULTS

At 156 weeks, the cumulative incidences of virological relapse and clinical relapse, and retreatment were higher in the off-TAF group (85.3%, 73.7%, and 76.6%, respectively) than in the off-entecavir group (58.0%, 45.5%, and 38.9%, respectively) (all p <0.001). Compared with the off-TDF group (74.6%, 64.4%, and 58.8%, respectively), the off-TAF group showed comparable rates of virological relapse (p=0.139) but significantly higher rates of clinical relapse (p=0.042) and retreatment (p=0.003). The median time to clinical relapse was earlier in patients discontinuing TAF than in those discontinuing entecavir or TDF (17, 42, and 24 weeks, respectively). Multivariable analysis demonstrated that TAF therapy was an independent risk factor for virological relapse, clinical relapse, and retreatment compared with entecavir, but not with TDF; these findings remained consistent after propensity score matching. Among patients with clinical relapse, HBeAg seroreversion was more frequent in the off-TAF group than in the off-entecavir (73.0% vs. 51.4%, p <0.001) and off-TDF groups (73.0% vs. 56.8%, p=0.029).

CONCLUSIONS

Discontinuation of TAF therapy was associated with earlier and higher HBV relapse rates compared with entecavir, but not TDF, in HBeAg-positive patients.