Switching to Entecavir >3 Months Before the End of Tenofovir-Based Therapy in Hepatitis B e Antigen-Negative Patients May Reduce Early Relapse and Hepatitis Flare

INTRODUCTION: Studies have shown that off-therapy clinical relapses occur much more frequently within 24 weeks and seems more severe in tenofovir disoproxil fumarate (TDF)-treated than in entecavir (ETV)-treated patients. A small retrospective study reported a significantly lower 24-week clinical relapse rate in 40 non-ETV (including 3 TDF)-treated patients after switching to ETV for ≥12 weeks before the end of therapy (EOT). To confirm the effect of the ETV-switching strategy, a retrospective cohort study was conducted. METHODS: TDF or tenofovir alafenamide (TAF) treatment in 18 hepatitis B e antigen-negative patients was switched to ETV for ≥12 weeks before EOT. Two control groups each 1:2 matched in age, sex, genotype, cirrhosis, baseline hepatitis B virus DNA, and quantitative hepatitis B surface antigen were recruited. All patients were followed up every 1-3 months for ≥6 months after EOT. RESULTS: Compared with the TDF/TAF-control, the incidence of clinical relapse and hepatitis flare by week 24 was lower (16.7 vs 58.3%; P = 0.009; 11.1 vs 50%; P = 0.013, respectively). The rate of hepatitis flare with alanine aminotransferase >10 times upper limit of normal was also lower than the TDF/TAF-control group (5.6 vs 33.3%; P = 0.040). All differences compared with the ETV-control group were nonsignificant. DISCUSSION: The results confirm that the timing of clinical relapse is associated with the last antiviral agent used before EOT. Furthermore, the ETV-switching strategy may reduce clinical relapse and hepatitis flare and the severity of hepatitis flare within 24 weeks after EOT. This strategy seems clinically useful and important for a safer cessation of TDF-based treatment.