Hepatitis B virus deoxyribonucleic acid in liver of chronic carriers. Correlation with serum markers and changes associated with loss of hepatitis B e antigen after antiviral therapy.

Patients with chronic hepatitis B receiving antiviral or immunomodulatory therapy were prospectively studied to determine the relationship between the state of hepatitis B virus deoxyribonucleic acid in liver and the levels of serum markers of hepatitis B virus infection. Hepatitis B virus deoxyribonucleic acid was quantitated and the molecular forms determined using molecular hybridization in two separate liver specimens taken at least 1 yr apart. All 30 patients initially had hepatitis B surface antigen and e antigen in serum and all had hepatitis B virus deoxyribonucleic acid, including replicative intermediate forms, present in liver. The amount of viral deoxyribonucleic acid in liver correlated significantly with the e antigen titer in serum. At the time of the second liver biopsy, e antigen was no longer detectable in the serum of 12 patients although all except 1 patient still had detectable hepatitis B surface antigen. In this group, the amount of hepatitis B virus deoxyribonucleic acid in liver had decreased significantly and replicative viral intermediates had disappeared. In contrast, among patients who remained e antigen-positive, the amount of viral deoxyribonucleic acid did not change appreciably and replicative intermediate forms were still detectable. These findings imply that in chronic hepatitis B, loss of e antigen is usually associated with resolution of hepatitis B virus replication.