Pregenomic HBV RNA and Hepatitis B Core‐Related Antigen Predict Outcomes in Hepatitis B e Antigen–Negative Chronic Hepatitis B Patients Suppressed on Nucleos(T)ide Analogue Therapy

HBcrAg and HBV RNA are sensitive biomarkers of continued transcription of cccDNA in HBeAg-negative patients despite marked HBV-DNA suppression by NA. These markers were predictors of severe alanine transaminase flares, after treatment withdrawal, and HBV-DNA reactivation. Their measurement during the natural history of hepatitis B, and on treatment with current and new agents, could characterize residual HBV-RNA transcription from cccDNA and assist drug development and disease management.