Kuhns M C, McNamara A L, Perrillo R P, Cabal C M, Campbel C R
Diagnostics Division, Abbott Laboratories, North Chicago, Ilinois 60064.
J Med Virol. 1989 Apr;27(4):274-81. doi: 10.1002/jmv.1890270404.
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.
在一项关于撤用泼尼松后给予α-干扰素治疗慢性乙型肝炎的随机对照试验中，对乙型肝炎病毒（HBV）复制的血清学标志物进行了评估。通过灵敏的定量溶液杂交试验测定了41例患者700多个系列血清样本中的HBV DNA水平。将结果与21例未治疗的对照者和20例治疗患者的HBV DNA聚合酶（DNAp）活性及乙肝e抗原（HBeAg）进行了比较。在治疗患者中，无反应者治疗前的平均HBV DNA值高于有反应者。在泼尼松治疗期间，有反应者的DNA水平平均升高2.1倍，无反应者升高1.4倍。在泼尼松和干扰素之间的2周休息间隔期，有反应者的DNA值平均下降57%。相比之下，无反应者的平均DNA值在同一间隔期未发生变化。从DNAp或HBeAg结果中未明显看出有反应者和无反应者之间的这种早期差异。在干扰素治疗期间，有反应者的HBV DNA变得检测不到，并在1年的随访期间保持阴性。无反应者的DNA在干扰素治疗期间降至基线的14%，但治疗后又升至治疗前水平。DNAp值一般与HBV DNA值平行，但DNAp活性比杂交试验结果显示出更大的变异性和更低的敏感性。HBeAg值与HBV DNA和DNAp独立变化，有反应者下降延迟得多。这些结果表明，当通过灵敏的溶液杂交试验进行定量测量时，HBV DNA是抗病毒药物对复制效果的早期预测指标。
