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  • Title: Quantitation of hepatitis B viral DNA by solution hybridization: comparison with DNA polymerase and hepatitis B e antigen during antiviral therapy.
    Author: Kuhns MC, McNamara AL, Perrillo RP, Cabal CM, Campbel CR.
    Journal: J Med Virol; 1989 Apr; 27(4):274-81. PubMed ID: 2656908.
    Abstract:
    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.
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