I. Medical Department, University Hospital Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
J Clin Virol. 2012 May;54(1):93-5. doi: 10.1016/j.jcv.2012.01.024. Epub 2012 Feb 24.
Nucleos(t)ides effectively halt disease progression in hepatitis B but require long-term medication.
To determine whether add-on of peg-IFN to an ongoing nucleos(t)ide therapy accelerates decline of HBsAg and induces seroconversion.
We observed HBsAg kinetics in 12 patients on a stable oral therapy with undetectable HBV-DNA who additionally received peg-IFN-alfa 2a as an individualized therapy. 3 patients were HBeAg positive. Mean baseline HBsAg was 4695 (range 16-15,120)IU/ml.
A continuous decline of HBsAg was observed in 2 patients. The slope, respectively, became detectable at week 8 or 16. HBsAg had dropped by 2.90log(10) or 4.25log(10) fold at week 48, and anti-HBs appeared at week 40 or 32. Patient A - HBe-positive, genotype A, F3 fibrosis - had been HBV-DNA negative for 10 months receiving entecavir plus tenofovir. Previous therapy with peg-IFN had been unsuccessful, but now the patient experienced HBeAg seroconversion at week 24. Patient B - HBeAg negative, genotype D, cirrhosis - had a low initial HBsAg level of 16U/l. Receiving entecavir, his HBV-DNA had previously been non-detectable for 27 months. In the remaining 10 patients HBsAg declined only by a mean of 0.09log(10) (range 0.01-0.25log(10)) after 8-24 (mean 16.4) weeks, and therefore, peg-IFN was stopped. No unexpected side effects were observed.
We observed that the add-on of peg-IFN induced HBsAg seroconversion in 2 out of 12 patients. Response rates may have been higher with prolongation of therapy. The add-on concept merits to be evaluated in a clinical trial.
核苷（酸）类药物可有效阻止乙型肝炎的疾病进展，但需要长期用药。
确定聚乙二醇干扰素-α（peg-IFN）联合正在进行的核苷（酸）类治疗是否能加速 HBsAg 下降并诱导血清转换。
我们观察了 12 例接受稳定的口服治疗且 HBV-DNA 不可检测的患者的 HBsAg 动力学，这些患者另外接受 peg-IFN-alfa 2a 作为个体化治疗。其中 3 例患者 HBeAg 阳性。平均基线 HBsAg 为 4695（范围 16-15120）IU/ml。
2 例患者观察到 HBsAg 持续下降。斜率分别在第 8 或 16 周开始可检测到。第 48 周时，HBsAg 下降了 2.90log（10）或 4.25log（10）倍，第 40 或 32 周时出现抗-HBs。患者 A-HBe 阳性，基因型 A，F3 纤维化-恩替卡韦加替诺福韦治疗 10 个月后 HBV-DNA 阴性。之前使用 peg-IFN 治疗无效，但现在患者在第 24 周时出现 HBeAg 血清转换。患者 B-HBeAg 阴性，基因型 D，肝硬化-初始 HBsAg 水平为 16U/l。接受恩替卡韦治疗，HBV-DNA 之前已不可检测 27 个月。在其余 10 例患者中，HBsAg 在第 8-24 周（平均 16.4 周）仅平均下降 0.09log（10）（范围 0.01-0.25log（10）），因此停止了 peg-IFN 治疗。未观察到意外的副作用。
我们观察到，在 12 例患者中有 2 例添加 peg-IFN 诱导 HBsAg 血清转换。延长治疗时间可能会使应答率更高。添加方案值得在临床试验中进行评估。
