干扰素和核苷合用可使部分慢性乙肝患者HBsAg降低

肝胆速递

Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B
干扰素和核苷合用可使部分慢性乙肝患者HBsAg降低

肝胆速递：12例患者中2例PEG干扰素和核苷治疗合用后HBsAg持续降低


Journal of Clinical Virology
Volume 54, Issue 1 , Pages 93-95, May 2012
Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B
Jens M. Kittner
Affiliations
I. Medical Department, University Hospital Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
      
    Martin F. Sprinzl    ,
    Annette Grambihler    ,
    Arndt Weinmann    ,
    Jörn M. Schattenberg    ,
    Peter R. Galle    ,
    Marcus Schuchmann

Abstract
Background

Nucleos(t)ides effectively halt disease progression in hepatitis B but require long-term medication.
Objectives

To determine whether add-on of peg-IFN to an ongoing nucleos(t)ide therapy accelerates decline of HBsAg and induces seroconversion.
Study design

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.
Results

A continuous decline of HBsAg was observed in 2 patients. The slope, respectively, became detectable at week 8 or 16. HBsAg had dropped by 2.90log10 or 4.25log10 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 0.09log10 (range 0.01–0.25log10) after 8–24 (mean 16.4) weeks, and therefore, peg-IFN was stopped. No unexpected side effects were observed.
Discussion

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.

背景

核苷（酸）的IDE有效遏制乙肝疾病进展，但需要长期服药。
目标

要确定是否对PEG-IFN一个持续的核苷（T）的IDE治疗的乙型肝炎表面抗原（HBsAg）加速下降，并诱导血清学转换。
研究设计

我们观察到一个稳定的口服治疗HBV-DNA检测不到，另外PEG-IFN-α2a的个体化治疗的12例乙肝表面抗原动力学。 3例患者HBeAg阳性。平均基线乙肝表面抗原为4695 IU /毫升（范围为16-15,120）。
结果

观察2例乙肝表面抗原的连续下降。的斜率，分别检测到8周或16周。由2.90log10和4.25log10倍的乙肝表面抗原下降48周时，抗-HBs出现在40周或32周。患者A  -  HBe阳性，基因型A，F3纤维化 - 10个月，接受恩替卡韦加替诺福韦HBV-DNA阴性。前PEG-IFN治疗是不成功的，但现在经历的患者在24周的HBeAg血清学转换。患者B  -  HBeAg阴性，基因型D，肝硬化 - 有一个较低的初始HBsAg水平16U/ L。接受恩替卡韦，他的HBV-DNA此前一直无法检测的27个月。由平均0.09log10（范围0.010.25log10），8-24（平均16.4）周后在余下的10名患者的HBsAg仅下降，因此，聚乙二醇化IFN被停止。没有意外的副作用进行观察。
讨论

我们观察到的附加的PEG-IFN诱导乙肝表面抗原血清学转换的12例患者中，有2。响应率可能会延长治疗。附加的概念优点，在临床试验中进行评估。

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