聚乙二醇干扰素α2b联合治疗HBeAg阳性慢性乙型肝炎患者替诺

StephenW

Hepatol Res. 2018 Jan 4. doi: 10.1111/hepr.13049. [Epub ahead of print]
Higher efficacy of Pegylated interferon-alpha 2b add-on therapy in HBeAg positive chronic hepatitis B patients on tenofovir monotherapy.Jindal A1, Vyas AK2, Kumar D3, Kumar G3, Sharma MK1, Sarin SK1.
Author information
1Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India.2Departments of Molecular and Cellular Medicine, Institute of Liver & Biliary Sciences, New Delhi, India.3Department of Clinical Research, Institute of Liver & Biliary Sciences, New Delhi, India.

AbstractBACKGROUND: Monotherapy with Peg-IFNα or nucleos(t)ide analogues(NA) currently approved for treating chronic hepatitis B(CHB) have limited efficacy. Studies on combination of Peg-IFN-α/NA have shown conflicting results. We investigated whether sequential adding-on Peg-IFNα to tenofovir enhances serological response rates.
METHODS: Treatment naïve, HBeAg-positive CHB patients with moderately elevated ALT(48 to 200IU/mL) were started on tenofovir(300 mg/day) and enrolled at week 12 in 1:1 ratio to either receive Peg-IFNα2b add-on(1.5mcg/kg/week) from week 12 to 36(n=53) or continue tenofovir-monotherapy(n=53). Both arms received tenofovir consolidation therapy until week 72. Primary end-point was HBeAg loss at week-72.
RESULTS: At week-72, rate of HBeAg loss was higher in Peg-IFNα2b add-on(35.8%) compared to tenofovir monotherapy (17%)(p=0.028; OR:2.73, 95%CI:1.09 to 6.79),considerably higher in patients with baseline HBV DNA level >6Log IU/ml(32.6% vs. 11.4%;p=0.021). Rates of HBV DNA loss(77.4% vs. 71.7%;p=0.51),ALT normalization (62.3% vs. 52.8%;p=0.32) and sustained virological response(20.8% vs. 11.3%;p=0.18) at week 72 were comparable in two groups. Significantly more patients in add-on group had >3Log HBV DNA reduction at week 36(92.5% vs. 66%,p=0.001). Four patients on Peg-IFNα2b add-on achieved HBsAg loss compared with one in tenofovir monotherapy. More than 2 log HBV DNA decline at week 4 lead to higher HBeAg loss at week 72 independent of treatment arms. No patient had treatment related adverse effects requiring treatment discontinuation.
CONCLUSIONS: 24 weeks of Peg-IFNα2b as add-on sequential regimen to tenofovir is safe and resulted in more HBeAg and HBsAg loss compared to tenofovir monotherapy in selected HBeAg positive patients. Viral load reduction followed by immune modulation is a potentially useful approach.

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KEYWORDS: HBV; Hepatitis viral; Therapy; and chronic HBV; tenefovir

PMID:29314573DOI:10.1111/hepr.13049

StephenW

Hepatol Res。 2018年1月4日，doi：10.1111 / hepr.13049。 [电子版提前打印]
聚乙二醇干扰素α2b联合治疗HBeAg阳性慢性乙型肝炎患者替诺福韦单药治疗的疗效更高。
Jindal A1，Vyas AK2，Kumar D3，Kumar G3，Sharma MK1，沙林SK1。
作者信息

1
    印度新德里肝胆科学研究所肝脏病研究所。
2
    分子和细胞医学系，印度新德里肝胆科学研究所。
3
    印度新德里肝胆科学研究所临床研究室。

抽象
背景：

目前批准用于治疗慢性乙型肝炎（CHB）的Peg-IFNα或核苷（t）同类物（NA）的单一疗法功效有限。 Peg-IFN-α/ NA的组合研究显示了相互矛盾的结果。我们调查是否连续添加Peg-IFNα替诺福韦提高血清学应答率。
方法：

初治的HBeAg阳性慢性乙型肝炎患者（替诺福韦300mg /天）开始ALT水平中等升高（48-200IU / mL），并在第12周以1：1的比例入组，接受Peg-IFNα2b加量（1.5 mcg / kg /周）12周至36周（n = 53）或继续替诺福韦单药治疗（n = 53）。两组接受替诺福韦巩固治疗至72周。主要终点是72周时的HBeAg消失。
结果：

在72周时，与替诺福韦单一疗法（17％）相比，Peg-IFNα2b加量（35.8％）的HBeAg消失率更高（p = 0.028; OR：2.73,95％CI：1.09-6.79）基线HBV DNA> 6Log IU / ml的患者（32.6％比11.4％; p = 0.021）。在一周内HBV DNA损失率（77.4％比71.7％; p = 0.51），ALT正常化率（62.3％比52.8％; p = 0.32）和持续病毒学应答率（20.8％比11.3％; p = 0.18） 72组在两组中相当。显着更多的患者在第36周有> 3Log HBV DNA降低（92.5％比66％，p = 0.001）。 Peg-IFNα2b添加物的4名患者与替诺福韦单一疗法中的1名患者相比，实现了HBsAg消失。在第4周时超过2log的HBV DNA下降导致在72周时HBeAg的消失高于治疗组。没有患者有治疗相关的不良反应，需要停药。
结论：

Peg-IFNα2b作为替诺福韦的附加序贯方案的24周是安全的，并且与选择的HBeAg阳性患者中的替诺福韦单一疗法相比导致更多的HBeAg和HBsAg消失。减少病毒负荷然后进行免疫调节是一种潜在的有用的方法。

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关键词：

HBV;肝炎病毒;治疗;和慢性HBV; tenefovir

结论：
    29314573
DOI：
    10.1111 / hepr.13049

neilhbver

mark。看来值得一试

antiHBVren

不错，希望能得出更为详细的报告