405
Switching to Peginterferon for Chronic
Hepatitis B Patients with Hepatitis B e Antigen
Seroconversion on Entecavir – a Prospective
Study
Henry Lik Yuen Chan1, Fiona Wai Sze Chan2, Aric Josun Hui3,
Michael Kin Kong Li4, Kam Hon Chan5, Grace Lai Hung Wong6,
Ching Kong Loo2, Angel Mei Ling Chim6, Chi Hang Tse7 and
Vincent Wai Sun Wong7, (1)Institute of Digestive Disease,
Department of Medicine and Therapeutics, and State Key
Laboratory of Digestive Disease, The Chinese University of
Hong Kong, Hong Kong, (2)Kwong Wah Hospital, (3)Alice
Ho Miu Ling Nethersole Hospital, (4)Tuen Mun Hospital,
(5)North District Hospital, (6)Department of Medicine and
Therapeutics, The Chinese University of Hong Kong, (7)The
Chinese University of Hong Kong
Background: Nucleos(t)ide analogues (NA) are effective
in suppressing hepatitis B virus (HBV) replication, but most
patients require long-term treatment. Previous studies have
reported approximately 9%-10% hepatitis B surface antigen
(HBsAg) loss among HBeAg-negative patients on entecavir
shifted to 1 year of peginterferon. With this background,
we hypothesized that patients who developed HBeAg
seroconversion on NA would benefit from immune modulation
by peginterferon treatment. This study evaluated the efficacy
and safety of switching to peginterferon among patients who
had HBeAg seroconversion on NA treatment. Methods: This
is a prospective, multi-center, single-arm, open-label study
(NCT 02068365). HBeAg-positive chronic hepatitis B patients
who developed HBeAg seroconversion during NA treatment
were studied. All patients received open-label peginterferon
alfa-2a 180mcg/week for 48 weeks, and NA was stopped
at week 4 of peginterferon treatment. Primary endpoint was
sustained response, which was defined as negative HBeAg,
positive anti-HBe and HBV DNA <2000 IU/ml at week 72.
Other secondary endpoints including HBsAg loss at week
72 were also studied. Results: Forty-one patients treated
by entecavir for 56±23 months were recruited. Sustained
response was achieved in 30 patients (73%, 95% confidence
interval 58%-84%). At week 72, 31 (76%) patients had HBeAg
seroconversion, 23 (56%) patients had undetectable HBV
DNA, 31 (76%) patients had normal ALT, and 6 patients (15%)
had HBsAg loss. Three patients had entecavir restarted at
week 68-72 due to elevated HBV DNA (143,004 to 637,860
IU/ml) with ALT of 36-67 U/l, and they were regarded as
treatment failure at week 72. On logistic regression analysis,
lower HBsAg level at baseline was the strongest predictor
of sustained response [odds ratio 0.12 (95% CI 0.02-0.77)]
and HBsAg loss [odds ratio of 0.08 (95% CI 0.01-0.62) ]. By
receiver operating characteristic (ROC) curve analysis, the
best HBsAg cutoff for sustained response was <1500 IU/ml
[area under ROC curve 0.75 (95% CI 0.58-0.92)] and that
for HBsAg loss was <500 IU/ml [area under ROC curve 0.88
(95% CI 0.75-1.00)]. Twenty-two of 25 (88%) patients with
baseline HBsAg <1500 IU/ml had sustained response. Five of
10 (50%) patients with baseline HBsAg <500 IU/ml developed
HBsAg loss. Five patients have laboratory abnormalities
requiring dose reduction of peginterferon. Peginterferon was
generally safe with no serious adverse event related to the
study drug. Conclusion: Switching to peginterferon can be
considered as a treatment option in NA-treated patients with
HBeAg seroconversion. The rate of HBsAg loss is high (15%),
and it can be up to 50% among those with HBsAg levels <500
IU/ml. 作者: StephenW 时间: 2018-10-16 08:36
405
切换到聚乙二醇干扰素治疗慢性病
乙型肝炎患者乙型肝炎抗原
恩替卡韦的血清学转换 - 一项前瞻性研究
研究
Henry Lik Yuen Chan1，Fiona Wai Sze Chan2，Aric Josun Hui3，
Michael Kin Kong Li4，Kam Hon Chan5，Grace Lai Hung Wong6，
Ching Kong Loo2，Angel Mei Ling Chim6，Chi Hang Tse7和
Vincent Wai Sun Wong，（1）消化系疾病研究所，
医学和治疗学系和国家重点
中国人民大学消化系疾病实验室
香港，香港，（2）广华医院，（3）爱丽丝
何妙龄那打素医院，（4）屯门医院，
（5）北区医院，（6）医学系
Therapeutics，香港中文大学，（7）The
香港中文大学
背景：Nucleos（t）ide类似物（NA）是有效的
在抑制乙型肝炎病毒（HBV）复制，但大多数
患者需要长期治疗。以前的研究有
据报道乙型肝炎表面抗原约占9％-10％
（HBsAg）在恩替卡韦的HBeAg阴性患者中丢失
转为1年的聚乙二醇干扰素。有了这样的背景，
我们假设发生HBeAg的患者
NA的血清转换将受益于免疫调节
通过聚乙二醇干扰素治疗。该研究评估了疗效
和转换为聚乙二醇干扰素的安全性
对NA治疗有HBeAg血清学转换。方法：这个
是一项前瞻性，多中心，单臂，开放标签的研究
（NCT 02068365）。 HBeAg阳性的慢性乙型肝炎患者
在NA治疗期间发生HBeAg血清学转换
被研究过。所有患者均接受开放式聚乙二醇干扰素
alfa-2a 180mcg /周，持续48周，并停止NA
在聚乙二醇干扰素治疗的第4周。主要终点是
持续反应，定义为阴性HBeAg，
72周时阳性抗-HBe和HBV DNA <2000 IU / ml。
其他次要终点，包括每周HBsAg丢失
还研究了72个。结果：41例患者接受了治疗
通过恩替卡韦招募56±23个月。持续
在30名患者中实现了反应（73％，95％的置信度
间隔58％-84％）。在第72周，31名（76％）患者患有HBeAg
血清学转换，23例（56％）患者无法检测到HBV
DNA，31例（76％）患者ALT正常，6例患者（15％）
HBsAg丢失了。三名患者重新开始使用恩替卡韦
第68-72周，由于HBV DNA升高（143,004至637,860
IU / ml）ALT为36-67 U / l，它们被认为是
在第72周治疗失败。在逻辑回归分析中，
基线时较低的HBsAg水平是最强的预测因子
持续反应[优势比0.12（95％CI 0.02-0.77）]
和HBsAg损失[比值比为0.08（95％CI 0.01-0.62）]。通过
接收机工作特性（ROC）曲线分析，
持续反应的最佳HBsAg截止值<1500 IU / ml
[ROC曲线下面积0.75（95％CI 0.58-0.92）]和
HBsAg损失<500 IU / ml [ROC曲线下面积0.88
（95％CI 0.75-1.00）]。 25例（88％）患者中有22例患有
基线HBsAg <1500 IU / ml有持续反应。五个
发生10例（50％）基线HBsAg <500 IU / ml的患者
HBsAg丢失。 5名患者有实验室异常
需要减少聚乙二醇干扰素的剂量。 Peginterferon是
一般安全，没有严重的不良事件
研究药物。结论：切换到聚乙二醇干扰素可以
被认为是NA治疗患者的治疗选择
HBeAg血清学转换。 HBsAg损失率很高（15％），
HBsAg水平<500的患者可高达50％
国际单位/毫升。作者: 齐欢畅 时间: 2018-10-16 21:44