Transition to HBeAg-negative chronic hepatitis B virus infection is associated with reduced cccDNA transcriptional activity

•A unique set of liver biopsies from patients with chronic hepatitis B was studied.•Quantification of viral DNA and RNA revealed disease stage-specific virological profiles.•HBeAg-negative chronic infection is associated with reduced cccDNA transcription.•Inhibition of replication downstream of pgRNA found in a subgroup of patients with HBeAg-negative chronic hepatitis and low viral load.