U.O. Epatologia-Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
J Hepatol. 2013 Dec;59(6):1153-9. doi: 10.1016/j.jhep.2013.07.017. Epub 2013 Jul 18.
BACKGROUND & AIMS: We investigated whether HBV genotype influences on-treatment HBsAg kinetics and/or the end-of-treatment HBsAg levels associated with long-term virological response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a±lamivudine in the Phase III trial.
All patients (n=230) who participated in long-term follow-up were included according to the availability of HBsAg level measurements. Long-term virological response was defined as HBV DNA ≤ 10,000cp/ml (1786IU/ml) at 5 years post-treatment. Genotype-specific end-of-treatment HBsAg levels associated with long-term virological response (identified by ROC analysis) were assessed in 199 patients with HBsAg measurements available at baseline and end-of-treatment. HBsAg kinetics according to genotype and long-term virological response were investigated in the 117 patients with additional samples available at weeks 12, 24, and 72.
Baseline HBsAg levels were significantly higher for A than B, C, and D genotypes (p<0.05). On-treatment HBsAg kinetics varied according to HBV genotype. The difference between responders and non-responders was greatest for genotype A from weeks 12-24; for genotypes B and D from baseline to week 12; there was no significant difference over any timeframe for genotype C. High positive predictive values for long-term virological response could be obtained by applying end-of-treatment genotype-specific cut-offs: 75%, 47%, 71%, and 75% for genotypes A (<400IU/ml), B (<50IU/ml), C (<75IU/ml), and D (<1000IU/ml), respectively.
On-treatment HBsAg kinetics vary between HBV genotypes. Genotype-specific monitoring timeframes and end-of-treatment thresholds could ameliorate response-guided treatment of HBeAg-negative chronic hepatitis B.
我们研究了 HBV 基因型是否会影响接受聚乙二醇干扰素 alfa-2a±拉米夫定治疗的 HBeAg 阴性慢性乙型肝炎患者的治疗中 HBsAg 动力学和/或与长期病毒学应答相关的治疗结束时 HBsAg 水平。
所有参加长期随访的患者（n=230）均根据 HBsAg 水平测量的可用性进行了纳入。长期病毒学应答定义为治疗后 5 年时 HBV DNA≤10,000cp/ml（1786IU/ml）。在 199 名基线和治疗结束时可测量 HBsAg 的患者中，通过 ROC 分析确定与长期病毒学应答相关的基因型特异性治疗结束时 HBsAg 水平（鉴定）。在另外 117 名有额外样本可在第 12、24 和 72 周时进行研究的患者中，根据基因型和长期病毒学应答研究 HBsAg 动力学。
与 B、C 和 D 基因型相比，A 基因型的基线 HBsAg 水平显著更高（p<0.05）。根据 HBV 基因型，治疗中 HBsAg 动力学有所不同。从第 12-24 周，应答者和非应答者之间的差异最大；从基线到第 12 周，B 和 D 基因型之间存在差异；在任何时间范围内，C 基因型均无显著差异。通过应用治疗结束时的基因型特异性切点，可以获得长期病毒学应答的高阳性预测值：基因型 A（<400IU/ml）、B（<50IU/ml）、C（<75IU/ml）和 D（<1000IU/ml）分别为 75%、47%、71%和 75%。
HBV 基因型之间的治疗中 HBsAg 动力学不同。基因型特异性监测时间框架和治疗结束时的切点可以改善 HBeAg 阴性慢性乙型肝炎的应答指导治疗。
