Serological markers of hepatitis B virus (HBV) replication were assessed in a randomized, controlled trial of
prednisone withdrawal followed by
alpha-interferon in the treatment of
chronic hepatitis B. HBV
DNA levels in more than 700 serial serum samples from 41 patients were determined by a sensitive and quantitative
solution hybridization assay. Results were compared with HBV
DNA polymerase (
DNAp) activity and
hepatitis B e antigen (
HBeAg) in 21 untreated controls and 20 treated patients. Among treated patients, the mean pretherapy HBV
DNA values were higher in nonresponders than in responders. During
prednisone treatment,
DNA levels increased an average of 2.1-fold in responders and 1.4-fold in nonresponders. During the 2-week rest interval between
prednisone and
interferon,
DNA values fell an average of 57% in responders. In contrast, the mean
DNA values in nonresponders did not change during the same interval. This early distinction between responders and nonresponders was not apparent from
DNAp or
HBeAg results. During
interferon treatment, HBV
DNA became undetectable in responders and remained negative during a 1-year follow-up.
DNA in nonresponders declined to 14% of baseline during
interferon treatment but increased to pretherapy levels
after treatment.
DNAp values generally paralleled HBV
DNA values, but
DNAp activity showed more variability and lower sensitivity than did the hybridization assay results.
HBeAg values varied independently of HBV
DNA and
DNAp with a much delayed decline in responders. These results indicate that HBV
DNA, when measured quantitatively by a sensitive
solution hybridization assay, is an early predictor of the effects of
antiviral agents on replication.