Combining HBV RNA and hepatitis B core-related antigen: guidance for safely stopping nucleos(t)ide analogues in HBeAg-positive chronic hepatitis B patients.

BACKGROUND: Safe nucleos(t)ide analogue discontinuation in chronic hepatitis B (CHB) is an unmet need. We aimed to investigate whether combining HBV RNA and hepatitis B core-related antigen (HBcrAg) could perform satisfactorily in predicting off-treatment outcomes. METHODS: The evaluation cohort included 127 HBeAg-positive patients from a multi-centre prospective trial who stopped telbivudine-based therapy after achieving HBeAg seroconversion and HBV DNA 48 weeks. As validation, 59 patients treated with entecavir or tenofovir before discontinuation were analysed. RESULTS: At the end of treatment (EOT), HBV RNA and HBcrAg were significant independent predictors of the clinical relapse risk. In the evaluation cohort, no clinical relapse occurred among patients with negative HBV RNA and HBcrAg /=4 log10 U/mL (high-risk group) experienced clinical relapse during 4-year post-treatment follow-up (P <0.001); the corresponding incidences in the validation cohort were 0% and 69.4% (P <0.001), respectively. More patients in the low-risk group achieved HBsAg loss than the other patients after treatment cessation (16.1% vs. 1.3%, P =0.002). CONCLUSION: Combining HBV RNA and HBcrAg performed satisfactorily in predicting clinical relapse and HBsAg loss after treatment cessation in HBeAg-positive CHB patients.