Off-tenofovir hepatitis flares in HBeAg-negative patients occur earlier, more frequent and severe than those off-entecavir therapies

Background & Aims: Clinical relapse occurs much earlier and more frequently in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients after stopping tenofovir (TDF) therapy than those off-entecavir (ETV). Clinical relapse may subside or progress to hepatitis flare which poses a safety concern. This study compared the incidence, timing and severity of hepatitis flares after stopping TDF and ETV. Methods: HBeAg-negative CHB patients who had stopped ETV or TDF were included in the study. Off-therapy hepatitis flare patterns were compared between off-ETV and off-TDF patients before and after propensity score matching (PSM). Results: The off-therapy hepatitis flares occurred more frequently (2-year: 58% vs 38%, P <.001) and much earlier (12 vs. 38 weeks, P <.001) in TDF group, with higher alanine aminotransferase (ALT) levels (after PSM: 536 vs. 419 U/L, P =.020) and two times rate of hepatic decompensation (4.0% vs. 2.1%, P =.322). The cirrhotic status [aHR: 20.531 (2.645-159.365), P =.004] and off-TDF [aHR: 5.530 (1.728-17.694), P =.004] were two independent predictors for hepatic decompensation. Conclusions: Hepatitis flare occurred more frequently, earlier, and more severe in off-TDF than off-ETV patients. More stringent off-therapy monitoring within 6 months off-TDF is mandatory whereas more attention is needed after 6 months off-ETV.