PERSISTENCE OF WILD-TYPE AND E-MINUS HEPATITIS-B VIRUS-INFECTION IN CHRONIC HEALTHY HBSAG ANTI-HBE POSITIVE CARRIERS/

We examined nine chronic healthy hepatitis B surface antigen/antibody to hepatitis Be carriers with consistently normal liver chemistries an d negative serum;hepatitis B virus-DNA. Liver biopsy, performed twice, 10-11 years apart in all patients, showed normal histology and negati ve hepatitis B core antigen. DNA extracted from the second liver biops y specimen, from 1 ml of serum from each patient and from an additiona l serum sample of 6 ml from two patients, was tested for pre-C/C and p re-S regions of hepatitis B virus-DNA by polymerase chain reaction amp lification. Viral sequences were found in six of nine liver DNA extrac ts. In four cases both pre-C/C and pre-S regions were amplified, while the pre-C/C alone and the pre-S alone were detected in one case each. Direct sequencing of the amplified DNAs revealed no significant genom ic changes in the pre-S and Core regions, while analysis of the pre-Co re demonstrated the presence of a double viral population (wild-type a nd ''e-defective'') in four cases, and only ''e-defective'' hepatitis B virus in one case. No hepatitis B virus genomes were revealed in the serum sample when DNA was extracted from 1 ml of serum, while viral s equences were detected in both extracts of 6 ml of serum, indicating t he presence of very low levels of viremia. These data suggest that epi somal hepatitis B virus-DNA may persist for years in the liver of chro nic healthy carriers in a latent state which may involve both wild-typ e and HBeAg-defective hepatitis B virus.