Is Vaccination a Risk Factor for Hepatitis B Reactivation?

I read with great interest the article titled "Risk of hepatitis B virus (HBV) reactivation in HBsAg-negative, anti-HBc-negative patients receiving rituximab for autoimmune diseases in HBV endemic areas, " published in Gut and Liver. 1 The study provides a valuable contribution by examining the effects of rituximab use on HBV reactivation in patients with autoimmune diseases.However, from a methodological perspective, I believe that including individuals vaccinated against hepatitis B in the study may not be appropriate for determining the risk of HBV reactivation.In the study, individuals who were vaccinated against hepatitis B at birth and those who were not were evaluated within the same analytical framework.However, when assessing the risk of HBV reactivation, it would be more appropriate to examine only individuals who have had a natural HBV infection or whose infection status is unknown.Since vaccinated individuals may have developed protective immunity against HBV, their risk of reactivation would naturally be lower.This situation may distort the study results and make it more challenging to determine the actual risk factors for HBV reactivation.Additionally, while anti-HBV antibody positivity in vaccinated individuals is considered a protective factor against HBV reactivation, it is difficult to distinguish whether this protection is due to natural immunity or vaccination.Therefore, the methods of this study may have been more appropriate if the vaccinated individuals were excluded from the analysis of HBV risk factors or at least considered as a separate subgroup.In this context, I recommend that future research analyze vaccinated and naturally immune individuals separately to allow for a clearer interpretation of study results.I kindly request your consideration of this methodological issue and appreciate your valuable contributions.