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.
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?作者: HBV-lost 时间: 2017-5-12 17:06
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吧作者: StephenW 时间: 2017-5-12 18:20
HBV-lost 发表于 2017-5-12 17:05
请问However, CR rate in baseline HBs Ag level
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。