Hepatitis B surface antigen, core-related antigen and HBV RNA: Predicting clinical relapse after NA therapy discontinuation

Background & Aims The safe discontinuation of nucleos(t)ide analogue therapy remains challenging in chronic hepatitis B. We investigated the potential role of quantitative hepatitis B surface antigen, hepatitis B core-related antigen and hepatitis B virus RNA at the end of treatment in predicting off-therapy relapse. Methods Patients who fulfilled the stopping criteria of the Asian Pacific Association for the Study of the Liver guideline were enrolled. Virological relapse was defined as hepatitis B virus DNA level greater than 2000 IU/mL, and clinical relapse was defined as virological relapse plus alanine aminotransferase level of more than twice the upper limit of normal. Results Ninety-two patients participated. The combination of end-of-treatment hepatitis B core-related antigen and hepatitis B virus RNA levels was most predictive of clinical relapse. Multivariate analysis revealed that end-of-treatment hepatitis B core-related antigen and hepatitis B virus RNA were independently associated with clinical relapse. During follow-up, no patients with undetectable hepatitis B core-related antigen (<3.0 log(10)U/mL) and hepatitis B virusRNA (<2.0 log(10)copies/mL) at end of treatment developed clinical relapse, in comparison with 22.9% and 62.5% patients with detectable levels of one or both biomarkers respectively. End-of-treatment quantitative hepatitis B surface antigen was linked to a likelihood of hepatitis B surface antigen clearance. Conclusions The combined hepatitis B core-related antigen and hepatitis B virus RNA assays at end of treatment were highly predictive of subsequent clinical relapse. These novel biomarkers could potentially be used to identify patients who could safely discontinue nucleos(t)ide analogue therapy.