拉米夫定长期维持应答患者血清乙型肝炎表面抗原水平的变化特点

目的 了解拉米夫定长期治疗下血清HBsAg的动态变化特点.方法 研究对象为HBeAg阳性、拉米夫定为初始抗病毒治疗且取得快速和持久(从治疗24周至观察期末HBV DNA持续检测不到)病毒学应答的慢性乙型肝炎患者.血清HBsAg定量检测采用雅培Architect方法,HBV基因型用直接测序法确定.结果 3年观察期间有26例(57.8%)患者发生HBeAg转阴(其中1例HBsAg转阴).治疗12周时血清HBsAg水平中位数降至基线的39.5%(P<0.01),但之后下降不明显.血清HBsAg的变化特征在HBcAg转阴或持续阳性的患者间相似.基因B型患者在治疗头12周血清HBsAg水平下降幅度较基因C型更大(75.5%比26.0%,P<0.05).在个体患者中,血清HBsAg的动态变化类型主要有双相型(治疗12和24周HBsAg低于基线的60%)和稳定型(治疗12和24周HBsAg高于基线的80%).基线血清HBsAg水平低(比数比值为0.020,95%可信区间为0.002~0.743,P<0.05)和基因C型感染(比数比值为8.206,95%可信区间为1.070~62.948,P<0.05)是血清HBsAg在拉米夫定长期治疗下下降不明显的主要因素.结论 血清HBsAg在拉米夫定快速和持久抑制HBV复制时主要表现为两种变化类型,并和HBV基因型关系密切.

Changes of serum HBsAg in HBeAg positive chronic hepatitis patients with sustained viral response to long-term lamivudine treatment

OBJECTIVE: HBsAg loss is rare in chronic hepatitis B patients, even in the patients with long-term nucleos(t)ide analogue therapy; therefore information about serum HBsAg kinetics will be of value in understanding this unusual occurrence. METHODS: Forty-five consecutive patients were studied, which were all HBeAg positive and never had antiviral therapy prior to lamivudine treatment; they then achieved rapid and good viral responses (defined as undetectable HBV DNA Roche Lightcycler, less than 1000 copies/ml] at treatment week 24 and they remained so until week 156). Abbott Architect HBsAg assay was used to quantify serum HBsAg and HBV genotypes were determined by direct sequencing. RESULTS: Twenty-six (57.8%) patients had HBeAg loss during the observation and one patient had HBsAg loss following his HBeAg seroconversion. Serum HBsAg levels decreased to 39.5% (median) of their baseline values at week 12, but no further significant reductions of serum HBsAg were found afterwards. Changes of serum HBsAg were comparable between patients with or without HBeAg loss. Serum HBsAg levels at their baselines were higher in HBV genotype B (HBV/B, n = 21) patients than in genotype C (HBV/C, n = 24) patients. HBV/B patients achieved many more HBsAg reductions than HBV/C ones (75.5 vs. 26.0%, median, P less than 0.05) in the first 12 treatment weeks, however HBsAg levels at week 156 were comparable between these two subgroups. HBsAg changes mainly showed two distinct patterns: a biphasic pattern (HBsAg levels were less than 60% of baseline ones at week 12 and 24, n = 25) and a maintaining pattern (HBsAg levels were greater than 80% of the baseline ones at week 12 and 24, n = 14). Logistic regression analysis showed that low serum HBsAg at baseline (odds ratio 0.020, 95% confidence interval 0.002-0.743, P less than 0.05) and HBV/C infection (odds ratio 8.206, 95% confidence interval 1.070-62.948, P less than 0.05) were the determinants of the occurrences of the maintaining pattern. CONCLUSION: In patients we examined, their HBsAg changes were mainly presented as either a biphasic pattern or a maintaining pattern, which were associated with HBV genotypes (B/C) but not with HBeAg loss. This might explain that why HBsAg loss is a rare occurrence even with long-term lamivudine therapy.