MOLECULAR-BASIS FOR PERSISTENT HEPATITIS-B VIRUS-INFECTION IN THE LIVER AFTER CLEARANCE OF SERUM HEPATITIS-B SURFACE-ANTIGEN

Hepatitis B virus (HBV) DNA has been detected by polymerase chain reac tion (PCR) in the liver of patients with resolved chronic HBV infectio n and sustained clearance of hepatitis B surface antigen (HBsAg) from serum. However, it is unknown whether the virus is transcriptionally a ctive at this time or if the covalently closed circular (CCC) replicat ive intermediate of HBV DNA can still be detected. Therefore, hepatic nucleic acid extracts from seven patients who had cleared serum HBsAg were assessed by (PCR) for either reverse-transcribed HBV RNA, or an i ntact direct repeat region of the HBV genome indicative of the CCC rep licative intermediate of HBV DNA, HBV transcripts were detected in fou r of seven patients in the study group, whereas an intact direct repea t region of the HBV genome was detected in three. Evidence for viral t ranscription and replication was more frequently detected in patients who had recently cleared serum HBsAg, but HBV RNA was also detected in one patient 5 years after HBsAg clearance, and an intact direct repea t region of HBV DNA was detected in another subject at nearly 4 years after resolution of disease. Therefore, hepatic HBV transcription may be associated with replicative intermediates of persistent HBV DNA in patients who have cleared HBsAg from serum, suggesting that, on occasi on, HBV may not be in a latent state but undergoing low-level replicat ion.