值得切换到PegIFN干扰素α-2a的患者达到病毒学抑制与恩替卡

StephenW

Letter to the Editor
Is it worthy of switching to PegIFN alfa-2a in patients achieving virological suppression with entecavir?

    Chuanghong Wu,

    Winston Dunn

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        doi:10.1016/j.jhep.2015.01.041
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        Qin Ning, Meifang Han, Yongtao Sun, Jiaji Jiang, Deming Tan, Jinlin Hou, Hong Tang, Jifang Sheng, Mianzhi Zhao
        Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: A randomised open-label trial (OSST trial)
        Journal of Hepatology, Volume 61, Issue 4, October 2014, Pages 777-784
             Purchase PDF (853 K)  Supplementary content

To the Editor:

We read with great interest the article “Switching from entecavir to PegIFN alfa-2a in patients with HBeAg positive chronic hepatitis B: A randomized open-label trial (OSST trial)” [1]. This elegant study assessed the rates of HBeAg seroconversion and HBsAg loss in patients with well-controlled HBV DNA replication and serum HBeAg <100 PEIU/ml on long-term entecavir (ETV) therapy after switching to a finite course of PegIFN alfa-2a. Qin Ning et al. [1] demonstrated that switching to a finite course of PegIFN alfa-2a significantly increased rates of HBeAg seroconversion and HBsAg loss and concluded this is a potential alternative to indefinite nucleos(t)ide analogue (NA) therapy.

Many chronic hepatitis B patients are treated with ETV in China. Some of them hope to stop this infinite treatment if a finite course of treatment can give similar or better outcomes with a reasonable cost and minimal adverse effects. In Shenzhen, patients receiving sequential therapy with NA and PegIFN are not rare. However, there are several concerns about this article and its approach. First, the absolute difference in HBeAg seroconversion rate was only 8.8%. In other words, the number to treat for one HBeAg seroconversion is 11. All these patients have to suffer the adverse effects of PegIFN. It is well known that hepatic decompensation and even death has been reported during IFN treatment. We should also pay special attention to the adverse effect of stopping of ETV. Hepatic decompensation or liver failure was not recorded in the study given the sample size. Recently, one of my patients developed acute on chronic liver failure during PegIFN treatment after stopping ETV and adefovir (ADV) which was reported on in a local hepatology meeting. The effect of an overlapping period of ETV and PegIFN on safety and efficacy remains unclear. Second, the other endpoints of HBV DNA suppression <1000 copies/ml and ALT normalization after 48 weeks of PegIFN treatment was unsatisfactory. These results might be worse after withdrawal of PegIFN therapy. Most of the patients had to resume ETV treatment, which is terrible news for a doctor to have to deliver to patients after a long course of PegIFN therapy. Third, sustained and profound viral suppression is the main goal of treatment. The fluctuation of ALT and HBV DNA in the sequential therapy may mimic the phenomena of viral resistance to NA. It has been reported that treatment related viral resistance blunts histologic responses [2] and increases the rate of hepatocellular carcinoma (HCC) even if rescue therapy is given [3]. Fourth, the cost of treatment should also be considered. The per capita disposable income is 18,311 RMB (≈2982 USD) in China 2013. The cost of 48 weeks of PegIFN treatment is about 50,000 RMB (≈8143 USD). Most of the treatment-naïve patients in China may find this treatment unaffordable. The cost of 48 weeks ETV is only one fifth of that. Fifth, the causative agent has not been identified in this randomized controlled study. The treatment arm underwent ETV withdrawal and PegIFN. Withdrawal of ADV after 4–5 years of therapy has been shown to result in 39% HBsAg loss in selected HBeAg negative patients [4]. To date, there has never been a parallel study in HBeAg positive patients, and there has never been a randomized control trial with PegIFN that involves a control arm with NA withdrawal only. We are anxiously waiting for such a study, we can no longer make the assumption that the treatment effect is entirely due to PegIFN. The correlation between early ALT elevation after withdrawal of ETV with HBeAg seroconversion and HBsAg loss supports this hypothesis. Finally, the benefit of HBeAg seroconversion should not be over emphasized. HBeAg seroconversion has long been regarded as an important treatment endpoint in hepatitis B therapy. However, with the prevalence of pre-core or core mutation HBV infection, HBeAg seroconversion is no longer an ideal endpoint. Recently, Jessica Liu et al. demonstrated that HBV DNA seroclearance, during the course of chronic hepatitis B, is the most significant factor in reducing risk for future HCC and HBeAg seroclearance will not reduce future HCC further [5]. Combination endpoint with HBeAg seroconversion and HBV DNA <1000 copies/ml may be more reasonable as the primary endpoint. We do not know if the significant difference between the two cohorts was lost with this endpoint.

In summary, as clinicians, after weighing the pros and cons, we do not think it is worthy of switching to PegIFN in patients achieving virological suppression with ETV, except if the patient refuse a long-term treatment.
Conflict of interest

The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

StephenW

给编辑的信
它是值得切换到PegIFN干扰素α-2a的患者达到病毒学抑制与恩替卡韦？

    长虹武，

    温斯顿·邓恩

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        DOI：10.1016 / j.jhep.2015.01.041
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        秦倪嗯，张美芳汉，孙永涛，嘉积江，谭德明，吉林侯，洪塘，Jifang盛，赵绵纸
        从恩替卡韦切换到PegIFN干扰素α-2a的患者HBeAg阳性慢性乙型肝炎：随机开放性试验（OSST试行）
        中华肝脏病杂志，第61卷，第4期，2014年10月，页777-784的
             购买PDF（853 K）的补充内容

给编辑：

我们阅读了极大的兴趣的文章“从与恩替卡韦HBeAg阳性慢性乙型肝炎切换到PegIFN干扰素α-2a的患者：一项随机开放试验（OSST试行）”[1]。切换到PegIFNα-2a的有限疗程后这家优雅的研究评估HBeAg血清学转换和HBsAg消失的速率患者的良好控制的HBV DNA复制与血清HBeAg <100 PEIU / ml的长期恩替卡韦（ETV）治疗。秦倪嗯等。 [1]显示，切换到PegIFN的有限当然干扰素α-2a显著提高HBeAg血清学转换和HBsAg消失率，并得出结论，这是一个潜在的替代无限期核苷（酸）类似物IDE（NA）治疗。

许多慢性乙型肝炎患者的治疗与教育电视在中国。他们中有些人希望能够停止这种无限的治疗，如果治疗的过程中有限的可以给类似或更好的结果有一个合理的成本和最小的不利影响。在深圳，接受序贯疗法与NA和PegIFN患者并不少见。不过，也有关于这篇文章和它的几个方法的关注。首先，在HBeAg血清转换率的绝对差值仅为8.8％。换言之，数字处理一个血清转换是11.所有这些患者有遭受PegIFN的不利影响。它公知的是肝功能失代偿，甚至​​死亡已在干扰素治疗的报道。我们还应该特别注意停止教育电视的不利影响。肝功能失代偿或肝功能衰竭并没有记录在给定的样本规模的研究。最近，我的一个病人停止和ETV阿德福韦（ADV），该报道在当地的肝病会议后在PegIFN治疗发展为急性慢性肝功能衰竭。 ETV与PegIFN对安全性和有效性的重叠周期的影响尚不清楚。二，HBV DNA抑制的其它端点<1000拷贝/ ml和ALT复常48周PegIFN的治疗后是不能令人满意的。撤离PegIFN治疗后，这些结果可能会更糟糕。大多数患者恢复ETV治疗，这是可怕的消息对医生不得不PegIFN治疗的漫长过程后提供给患者。三，持续而深刻的抑制病毒是治疗的主要目标。 ALT和HBV DNA中的序贯疗法的波动可能模仿病毒耐药的现象NA。据报道，治疗相关的病毒抗性减弱的组织学反应[2]和增加肝细胞癌（HCC）的速率，即使抢救治疗给予[3]。第四，治疗费用也应考虑。人均可支配收入为18311元人民币（≈2982美元）在2013年中国48周PegIFN治疗的费用约50000元人民币（≈8143美元）。大多数初治患者在中国可能会发现这种治疗负担不起。 48周ETV成本仅为五分之一。第五，病原体尚未确定在这个随机对照研究。治疗组接受ETV撤离和PegIFN。撤出ADV后4-5年的治疗已经显示出导致39％的HBsAg消失在选定HBeAg阴性患者[4]。迄今为止，从未有过一个类似的研究在HBeAg阳性患者，并且从未有过的随机对照试验与PegIFN，涉及控制臂只有NA撤出。我们都在焦急地等待着这样的研究，我们不能再作一个假设，治疗效果完全是由于PegIFN。 ETV的撤出HBeAg血清转换和HBsAg消失后早期ALT升高之间的相关性支持这一假说。最后，HBeAg血清学转换的好处不应该过分强调。 HBeAg血清学转换一直被认为是乙肝治疗的一个重要的治疗终点。然而，与前核心或核心突变HBV感染的患病率，HBeAg血清学转换不再是一个理想的终点。近日，杰西卡刘等人。证实HBV DNA的血清清除，慢性乙型肝炎的过程中，是在减少的风险为未来的肝癌和HBeAg血清清除不会降低未来肝癌最显著因子进一步[5]。与HBeAg血清转换和HBV DNA <1000拷贝组合端点/ ml的可能是作为主要终点更为合理。我们不知道，如果两个队列之间的显著差异失去了与这个端点。

总之，作为临床医生，在权衡得失后，我们不认为这是值得切换到PegIFN的患者达到病毒学抑制恩替卡韦，除非患者拒绝长期治疗。
利益冲突

作者宣称，他们没有任何披露有关资金或利益冲突对于这部书稿。

咬牙硬挺

感谢分享

682256

归纳，作为临床医生，我们认为，在恩替治疗取得病毒抑制效果后，权衡利弊，在这时转换为干扰素治疗是不值得的，除非是拒绝长期治疗的病人。

682256

应该有汉语原文吧？

StephenW

回复 682256 的帖子

不大可能，这是给国际肝脏期刊编辑的一封信.

遥望曙光

看不太懂，是不是现在主张，核苷类药物控制后，再用干扰素？

咬牙硬挺

感谢分享