序贯口服抗病毒治疗聚乙二醇干扰素-α未能显着提高HBsAg的

StephenW

                                   Gut 2013;62:A189-A190 doi:10.1136/gutjnl-2013-304907.431

    Liver

PWE-143 Sequential Oral Anti-Viral Therapy Following Pegylated-Interferon-Alpha Failure Significantly Increases Hbsag Decline

    U S Gill1,
    L Payaniandy2,
    J Schulz2,
    D Payaniandy2,
    V Ross3,
    Y Kallis2,
    P Kooner2,
    R Marley2,
    G R Foster1,
    P T Kennedy1

+ Author Affiliations

    1The Liver Unit, Blizard Institute, Barts and The London SMD, QMUL
    2Hepatology
    3Pharmacy, Barts Health NHS Trust, London, UK

Abstract

Introduction Tenofovir and Entecavir are potent oral antivirals (OAV’s) and leading agents in the treatment of Chronic Hepatitis B (CHB). Despite this, they have limited ability to reduce HBsAg, thus indefinite or life-long therapy is mandated as these drugs rarely achieve immunological control. Pegylated-Interferon-Alpha (PEG-IFNα) is associated with better rates of HBsAg decline, but only a minority of patients achieve sustained immune control. New strategies to reduce HBsAg and achieve immune control, including combination PEG-IFNα & OAV are under investigation at present. Here we report data on treatment response in a cohort receiving sequential OAV therapy following PEG-IFNα failure.

Methods 55 patients (male = 41), median age 31 (range 18–55) were treated with PEG-IFNα over the course of the study. 13 patients remain on therapy and 5 patients discontinued due to poor response or intolerance. 37 patients, HBeAg positive (n = 29), completed 48 weeks PEG-IFNα and were included in the analysis. 23/37 patients (HBeAg positive = 18), following treatment with PEG-IFNα were considered non-responders and treated with sequential OAV therapy. Treatment response in this cohort was compared with 60 patients, (male = 54), median age 45 (range 21–70) receiving OAV monotherapy over a 12-month period. Serum ALT, HBV DNA and HBsAg were quantified at baseline and longitudinally in both cohorts.

Results In the sequential therapy group, baseline median ALT was 60 IU/L (range 31–194) and median HBV DNA 5.15 logIU/ml compared with 43 IU/L and 3.43 logIU/ml respectively for the OAV monotherapy group. ALT normalisation and reduction in HBV DNA to undetectable levels was similar in both groups over follow-up (p- = n.s). Following 12-months of OAV monotherapy the decline in HBsAg in this group overall was 0.06 logIU/ml compared to baseline (p = n.s). In patients receiving sequential OAV therapy there was a significant decline in HBsAg over follow-up compared to baseline (0.65 log IU/ml, p = 0.0001). In addition 4/18 HBeAg positive patients seroconverted on sequential therapy and 1 patient cleared HBsAg.

Conclusion Sequential OAV therapy following treatment failure with PEG-IFNα is associated with greater reductions of HBsAg than PEG-IFNα alone or OAV monotherapy. This suggests PEG-IFNα may prime the immune response, even in the context of treatment failure, leading to better responses with sequential OAV therapy. Further studies are needed to confirm this finding and determine whether a similar priming effect is observed with shorter courses of PEG-IFNα in line with current PEG-IFNα stopping rules.
            

StephenW

替诺福韦和恩替卡韦是有效的口服抗病毒药物（OAV）和领先剂在治疗慢性乙型肝炎（CHB）。尽管这样，他们只有有限的能力，以减少乙肝表面抗原，从而无限期或终身治疗的任务，因为这些药物很少能​​达到免疫控制。聚乙二醇干扰素-α（PEG-IFNα）是与更​​好的HBsAg下降率，但只有少数患者实现持久的免疫控制。新战略，以减少HBsAg和实现免疫控制，包括组合PEG-IFNα与OAV，目前正在调查中。在这里，我们对治疗反应的报告数据，在一组连续接收OAV治疗后，PEG-IFNα失败。

方法对55例（男= 41），中位年龄为31岁（范围18-55），PEG-IFNα治疗，在研究过程中。维持治疗13例，5例因反应不佳或不能耐受终止。 37例患者，HBeAg阳性组（n = 29），完成了48周PEG-IFNα和纳入分析。 23/37的患者（HBeAg阳性= 18），被认为是与PEG-IFNα治疗后无应答和处理顺序OAV治疗。在这个队列进行了比较与治疗反应60例（男= 54），平均年龄45（21-70）单药治疗超过12个月的时间内接受OAV。量化基线血清ALT，HBV DNA和HBsAg和纵向两个同伙。

结果序贯治疗组，基线ALT中位数为60 IU / L（范围31-194）和中位数HBV-DNA 5.15 logIU /毫升与43 IU / L和3.43 logIU /毫升分别为OAV单药治疗组相比。超过跟进两组（P = NS），ALT复常和HBV DNA下降到检测不到的水平相似。继12个月的OAV单一，在本组中HBsAg下降整体是0.06 logIU /毫升相比，基线（P = NS）。在连续接收OAV治疗的患者中，有一个基线（0.65日志IU /毫升，P = 0.0001）相比显着下降，乙肝表面抗原，随访。此外，4/18 HBeAg阳性患者血清转变序贯治疗，1例HBsAg清除。

相关结论顺序OAV疗法治疗后失败的PEG-IFNα比PEG-IFNα单独或OAV单药治疗的HBsAg更大的削减。这表明PEG-IFN-α可素的免疫反应，即使在治疗失败的情况下，导致更好的响应顺序OAV治疗。还需要进一步研究来证实这一发现，并确定是否有类似的的促发效果观察与短疗程的PEG-IFNα与当前PEG-IFNα停止的规则。

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