Lopez-Alcorocho J M, Cabrerizo M, Bartolome J, Cotonat T, Carreño V
Hepatology Unit, Fundación Jiménez Díaz, Madrid, Spain.
J Viral Hepat. 1995;2(6):279-84. doi: 10.1111/j.1365-2893.1995.tb00042.x.
To assess the effects of prednisone and interferon on the distribution of hepatitis B virus (HBV) precore mutants, nine hepatitis B e antibody (HBeAb)-positive patients with HBV chronic infection were studied. Patients were treated with prednisone (30 mg day-1 for 4 weeks, followed by 20 mg day-1 for 2 weeks and by 10 mg day-1 for 1 week), followed by recombinant interferon-alpha (15 MU thrice per week) for 6 months, without a clearance period. The HBV precore region was amplified by polymerase chain reaction (PCR) and distribution of the precore mutants was determined by hybridization of PCR products. Moreover, the glucocorticoid-responsive element (GRE) was sequenced to determine whether changes in the sequence were produced at the end of prednisone treatment. During prednisone treatment, changes in alanine transaminase (ALT) were observed in only two patients, in who ALT decreased to nearly normal values. In three patients ALT normalized at the end of interferon treatment. At baseline, wild-type HBV alone was detected in one patient, while seven patients were infected by a mixture of wild-type and precore mutants, predominantly wild type. At the end of prednisone treatment, two patients were infected by only wild-type HBV. The proportion of precore mutants decreased in three cases, while no changes were observed in three. At the end of interferon treatment, the precore mutant proportion decreased in the three responders, while tending to increase or remain unchanged in the rest. No significant changes in GRE sequence were found as a result of prednisone treatment. Our results would appear to confirm the role of the immune system in the selection of precore mutants.
为评估泼尼松和干扰素对乙型肝炎病毒（HBV）前核心突变体分布的影响，我们研究了9例慢性HBV感染且乙型肝炎e抗体（HBeAb）阳性的患者。患者先接受泼尼松治疗（第1至4周为每日30 mg，随后2周为每日20 mg，最后1周为每日10 mg），之后接受重组α干扰素（每周3次，每次15 MU）治疗6个月，期间无洗脱期。通过聚合酶链反应（PCR）扩增HBV前核心区，并通过PCR产物杂交确定前核心突变体的分布。此外，对糖皮质激素反应元件（GRE）进行测序，以确定在泼尼松治疗结束时序列是否发生变化。在泼尼松治疗期间，仅2例患者观察到丙氨酸转氨酶（ALT）变化，其ALT降至接近正常水平。3例患者在干扰素治疗结束时ALT恢复正常。基线时，仅1例患者检测到野生型HBV，7例患者感染野生型和前核心突变体的混合株，以野生型为主。在泼尼松治疗结束时，2例患者仅感染野生型HBV。3例患者前核心突变体比例下降，3例无变化。在干扰素治疗结束时，3例有反应的患者前核心突变体比例下降，其余患者则有增加或保持不变的趋势。泼尼松治疗后GRE序列未发现明显变化。我们的结果似乎证实了免疫系统在选择前核心突变体中的作用。
