Liver and Bile
J Gastroenterol Hepatol. 2022;37(11):2164–72
A switch from tenofovir to entecavir prior to hepatitis B treatment cessation is associated with a reduced risk of off-therapy relapse: An observational study
Background and aim: In hepatitis B e-antigen (HBeAg)-negative chronic hepatitis B (CHB) patients, clinical relapse occurs more frequently, much earlier and often more severely after stopping tenofovir (TDF) and other nucleos(t)ide analogues (NAs) than after stopping entecavir (ETV). It is unknown whether off-NA hepatitis flare can be alleviated by switching from one NA to another.
Methods: HBeAg-negative CHB patients who had stopped NA according to the Asian Pacific Association for the Study of the Liver (APASL) stopping rule and had been followed-up for > 48 weeks after NA cessation were recruited. Patients were classified as 4 groups: ETV monotherapy (mono-ETV), TDF monotherapy (mono-TDF), switched to ETV (switch-ETV), and switched to TDF (switch-TDF). Both switch groups had switched to the replacement NA > 12 weeks prior to end of therapy. Propensity score matching (PSM) was performed to minimize confounders among groups. Cox regression analysis was used to identify risks factors for off-NA clinical relapse and flares.
Results: A total of 1309 patients (1022 mono-ETV, 219 mono-TDF, 40 switch-ETV and 28 switch-TDF) were enrolled. The median time to clinical relapse was 39, 13, 38 and 14 weeks in mono-ETV, mono-TDF, switch-ETV and switch-TDF, respectively (p < 0.001). After PSM, the mono-ETV (adjusted hazard ratio [aHR] = 0.39, p < 0.001) and switch-ETV patients (aHR = 0.41, p = 0.003) had both significantly later occurrence and lower rates of clinical relapse and flare.
Conclusion: In summary, the incidence and timing of clinical relapse was determined by entecavir (ETV) or tenofovir in the last 3 months prior to end of treatment. Patients treated with non-ETV-nucleos(t)ide analogue (NA) switched to ETV > 12 weeks before end of the original NA therapy may reduce/defer clinical relapse.