附加干扰素α-2a治疗慢性乙型肝炎恩替卡韦治疗。

StephenW

Hepat Res Treat. 2017;2017:2093847. doi: 10.1155/2017/2093847. Epub  2017 Apr 11.
Add-on Pegylated Interferon Alpha-2a Therapy in Chronic Hepatitis B Japanese Patients Treated with Entecavir.Tamai H1, Ida Y1, Shingaki N1, Shimizu R1, Fukatsu K1, Itonaga M1, Yoshida T1, Maeda Y1, Moribata K1, Maekita T1, Iguchi M1, Kato J1, Kitano M1.
Author information
1Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama 641-0012, Japan.

AbstractEntecavir requires long-term administration. Pegylated interferon (PEG-IFN) therapy leads to significant reduction of hepatitis B surface antigen (HBs Ag) levels. This study aimed to assess the safety and efficacy of adding PEG-IFN-α-2a to entecavir toward cessation of entecavir. A total of 23 patients treated with entecavir underwent add-on PEG-IFN-α-2a therapy (90 μg per week) for 48 weeks. Viral response (VR) was defined as more than 50% reduction of baseline hepatitis B surface antigen (HBs Ag) level at 72 weeks from the start of therapy. Complete response (CR) was defined as the decline of HBs Ag levels <100 IU/mL. Hepatitis B e antigen (HBe Ag) seroconversion rate was 25% (2/8), and VR rate was 52% (12/23). CR was observed in four patients (17%). However, CR rate in baseline HBs Ag level <2000 IU/mL and HBe Ag negative patients was 50% (4/8). Univariate analysis showed that the percentage of HBs Ag level reduction at week 12 was significantly associated with VR. The area under the curve value was 0.848. Adding PEG-IFN-α-2a to entecavir has limited efficacy. The percentage reduction of HBs Ag level at week 12 may be a useful predictor for VR.


PMID:28487770PMCID:PMC5405394DOI:10.1155/2017/2093847

StephenW

肝癌治疗2017; 2017：2093847。 doi：10.1155 / 2017/2093847。 Epub 2017 Apr 11。
附加聚乙二醇化干扰素α-2a治疗慢性乙型肝炎日内瓦恩替卡韦治疗。
Tamai H1，Ida Y1，Shingaki N1，Shimizu R1，Fukatsu K1，Itonaga M1，Yoshida T1，Maeda Y1，Moribata K1，Maekita T1，Iguchi M1，Kato J1，Kitano M1。
作者信息
附加聚乙二醇化干扰素α-2a的治疗慢性乙型肝炎日内瓦恩替卡韦治疗。
1
    和歌山医科大学内科医学系811-1 Kimiidera，和歌山市，和歌山641-0012，日本。

抽象

恩替卡韦需要长期管理。聚乙二醇化干扰素（PEG-IFN）治疗导致乙型肝炎表面抗原（HBs Ag）水平显着降低。本研究旨在评估添加PEG-IFN-α-2a对恩替卡韦停止恩替卡韦的安全性和有效性。总共23例接受恩替卡韦治疗的患者接受PEG-IFN-α-2a治疗（每周90μg）48周。病毒反应（VR）定义为从治疗开始72周时，基线乙肝表面抗原（HBs Ag）水平降低了50％以上。完全反应（CR）被定义为HBs Ag水平<100 IU / mL的下降。乙肝e抗原（HBe Ag）血清转化率为25％（2/8），VR率为52％（12/23）。 4例患者观察到CR（17％）。然而，基线HBs Ag水平<2000 IU / mL和HBe Ag阴性患者的CR率为50％（4/8）。单变量分析显示，第12周HBs Ag水平降低的百分比与VR显着相关。曲线下面积为0.848。将PEG-IFN-α-2a加入恩替卡韦具有有限的功效。第12周HBs Ag水平的降低可能是VR的有用预测因子。

结论：
    28487770
PMCID：
    PMC5405394
DOI：
    10.1155 /二百〇九万三千八百四十七分之二千〇一十七

HBV-lost

请问However, CR rate in baseline HBs Ag level <2000 IU/mL and HBe Ag negative patients was 50% (4/8). 这句的意思是HBs Ag level <2000 IU/mL 时，治愈率为50%吗？

HBV-lost

Complete response (CR) was defined as the decline of HBs Ag levels <100 IU/mL. 这个意思也不是HBs Ag为0吧

StephenW

HBV-lost 发表于 2017-5-12 17:05
请问However, CR rate in baseline HBs Ag level

不是, 50%达到 HBsAg  < 100 iu/ml.

StephenW

回复 HBV-lost 的帖子

在这项研究中，0％HBsAg清除.
记住病人人数很少, PegIFN只有48周.

The CR rate in the present study was low (17%), and the disappearance of HBs Ag or HBs seroconversion was not seen. If the aim of add-on PEG-IFN-α-2a therapy was to safely discontinue entecavir, this regimen would be considered insufficient. Regarding the efficacy of adding PEG-IFN to NA therapy, Ouzan et al. reported that the addition of 180 μg of PEG-IFN-α-2a for a maximum of 96 weeks based on HBsAg-titer monitoring led to a loss of HBsAg and cessation of NA therapy in six out of ten patients (60%), with no relapse [17]. Marcellin et al. reported that the rates of HBs Ag loss were significantly higher in the group treated with tenofovir plus PEG-IFN for 48 weeks than in the group (6.5%) treated with tenofovir plus PEG-IFN for 16 weeks and tenofovir for 32 weeks (0.5%) [18]. Therefore, longer-term add-on PEG-IFN-α-2a therapy would be needed for the cessation of NA. However, adverse effects are common in high-dose IFN therapy especially in cirrhotic patients and the elderly. Adequate doses of PEG-IFN for long-term treatment should be clarified in the future.

In the present study, HBs Ag levels in most of the patients were decreased in varying degrees during add-on PEG-IFN-α-2a, and the decrease continued even after add-on PEG-IFN-α-2a therapy. Furthermore, this reducing effect of HBs Ag level gradually appeared 12 weeks after the start of add-on PEG-IFN-α-2a. This phenomenon is significant to the study because it is not seen in NA therapy. It was reported that high HBs Ag level is a risk factor for carcinogenesis in inactive HBV carriers with negative HBe Ag and low HBV-DNA level [19]. As most of the patients in the present study have shown similar condition with inactive low HBV-DNA carrier by long-term entecavir therapy, the reduction effect of HBs Ag by adding PEG-IFN-α-2a on entecavir may lower carcinogenic risk. To confirm this, further study is needed.

Recent multicenter randomized trial of 180 μg of PEG-IFN-α-2a with entecavir for patients with HBe Ag positive chronic hepatitis B for 48 weeks showed that the rate of HBe Ag loss at 72 weeks was 32%, which was higher than the 18% in entecavir monotherapy [20]. However, no HBs Ag seroconversion was seen at 72 weeks even in add-on therapy. Although the number of HBe Ag positive patients in the present study was small, the rate of HBe Ag loss by add-on therapy was 25%, with no HBs Ag loss or seroconversion seen in HBe Ag positive patients. Accordingly, it might be difficult that add-on PEG-IFN-α-2a for HBe Ag positive patients treated with entecavir achieves HBs Ag disappearance. In contrast, there are no reports of HBs Ag loss or seroconversion due to the addition of PEG-IFN-α-2a to entecavir for HBe Ag negative patients. In the present study, CR rate in HBe Ag negative patients was 27%. Furthermore, in the case of patients with HBe Ag negative and baseline HBs Ag level <2000 IU/mL, the CR rate rose to 50%. Therefore, it is conceivable that optimal clinical indication of add-on PEG-IFN-α-2a therapy for patients treated with entecavir is considered as patients with HBe Ag negative and low HBs Ag level (at least <2000 IU/mL).
本研究的CR率低（17％），未见HBs Ag或HBs血清转换的消失。如果附加PEG-IFN-α-2a治疗的目的是安全停用恩替卡韦，则该方案将被认为是不充分的。关于添加PEG-IFN对NA治疗的疗效，Ouzan等报告说，基于HBsAg滴度监测，最多可以添加180μg的PEG-IFN-α-2a导致HBsAg的损失和NA治疗的丧失，在10例患者中有6例（60％），其中无复发[17]。 Marcellin等人报道说，使用替诺福韦加PEG-IFN治疗的组中HBsAg的损失率显着高于用替诺福韦加PEG-IFN治疗16周的组（6.5％）和替诺福韦32周（0.5％ ）[18]。因此，需要长期的添加PEG-IFN-α-2a治疗来停止NA。然而，高剂量IFN治疗，特别是肝硬化患者和老年人的不良反应是常见的。未来应明确适当剂量的PEG-IFN用于长期治疗。

在本研究中，大多数患者的HBs Ag水平在加入PEG-IFN-α-2a期间呈不同程度的降低，即使在加入PEG-IFN-α-2a治疗后，其水平持续下降。此外，加入PEG-IFN-α-2a开始后12周，HBs Ag水平的这种降低作用逐渐出现。这种现象对于研究是重要的，因为在NA治疗中没有看到。据报道，高HBs Ag水平是阴性HBe Ag和低HBV-DNA水平较低的无活性HBV携带者致癌作用的危险因素[19]。由于本研究中大多数患者通过长期恩替卡韦治疗显示与无效低HBV-DNA载体相似的病情，HBs Ag通过添加PEG-IFN-α-2a对恩替卡韦的降低作用可能降低致癌风险。为了证实这一点，需要进一步的研究。

对于HBe Ag阳性慢性乙型肝炎患者48周的180mg PEG-IFN-α-2a与恩替卡韦的近期多中心随机试验显示，72周时HBe Ag损失率为32％，高于18例恩替卡韦单药治疗[20]。然而，即使在附加治疗中，72周时也没有观察到HBs Ag血清学转换。尽管本研究中HBe Ag阳性患者的数量较少，但HBe Ag阳性患者的HBe Ag损失或HBsAg阳性患者的HBe Ag损失或血清学转换率均为25％。因此，用恩替卡韦治疗的HBe Ag阳性患者的附加PEG-IFN-α-2a可能难以实现HBs Ag消失。相比之下，由于向HBe Ag阴性患者的恩替卡韦添加了PEG-IFN-α-2a，没有报道HBs Ag的丧失或血清学转换。在本研究中，HBe Ag阴性患者的CR率为27％。此外，在HBe Ag阴性和基线HBs Ag水平<2000 IU / mL的患者中，CR率升至50％。因此，可以想象，用恩替卡韦治疗的患者的附加PEG-IFN-α-2a治疗的最佳临床适应症被认为是HBe Ag阴性和低HBs Ag水平（至少<2000IU / mL）的患者。

HBV-lost

回复 StephenW 的帖子

非常感谢，样本少，时间短，好像效果也不是特别好

咬牙硬挺

感谢分享