AASLD2018[417]慢性肝炎的治疗停止 B：通过预测非处

StephenW

417
Treatment Cessation in Chronic Hepatitis
B: Predicting Off-Treatment Durability Via
Combination of Viral Markers
Wai Kay Walter Seto1, Kevin Liu2, Lung-Yi Mak3, Ka Shing
Cheung4, Danny Ka Ho Wong5, Fen Liu4, James Fung6, Ching
Lung Lai4 and Man-Fung Yuen7, (1)Queen Mary Hospital,
Hong Kong, Hong Kong, (2)Medicine, Queen Mary Hospital,
Hong Kong, (3)Queen Mary Hospital, (4)Medicine, The
University of Hong Kong, (5)State Key Laboratory for Liver
Research, The University of Hong Kong, (6)Medicine, Queen
Mary Hospital, (7)Department of Medicine, University of Hong
Kong, Queen Mary Hospital
Background: Treatment cessation in nucleoside analoguetreated
chronic hepatitis B (CHB) can be associated with high
rates of disease relapse. Serum hepatitis B surface antigen
(HBsAg) levels have been suggested as a marker reflecting
immune control. We investigated the efficacy of treatment
cessation and predictors of successful off-treatment durability
in CHB patients with low serum HBsAg levels. Methods: We
prospectively recruited consecutive non-cirrhotic HBsAgpositive
patients treated with entecavir or tenofovir with serum
HBsAg <200 IU/mL and fulfilling the European Association for
the Study of the Liver (EASL) criteria for treatment cessation.
Liver biochemistry, serum HBV DNA, HBsAg and hepatitis B
core-related antigen (HBcrAg) were measured at baseline
and every 6 weeks up to week 48 after treatment cessation.
HBV reactivation was defined as HBV DNA >2,000 IU/mL.
Treatment was re-initiated in patients with HBV reactivation
and elevated alanine aminotransferase (ALT) (>40 U/L), or
with two consecutive HBV DNA readings of >2,000 IU/mL (the
second measurement taken within two weeks). Results: In
this interim analysis, 103 patients (mean age 56.4 ±10.9 years,
67.0% male) with a mean nucleoside analogue treatment
duration of 7.1 (±2.0) years were recruited. Median duration
of follow-up after treatment cessation was 42 (IQR 29-48)
weeks. Median baseline HBsAg and HBcrAg levels were 55.3
(16.9-89.5) IU/mL and 1.1 (0.3-4.7) kU/mL respectively. The
cumulative rate of HBV reactivation at 48 weeks, calculated
by the Kaplan-Meier method, was 59.2%. Among 78 patients
with available viral measurements, baseline serum HBsAg
≤10 IUmL, compared to HBsAg >10 IU/mL, had a significantly
lower cumulative rate of HBV reactivation (31.6% versus
66.1%, p=0.023). A lower baseline serum HBsAg level, via Cox
regression, was associated with significantly lower rates of
HBV reactivation (p=0.047, OR 1.005, 95%CI 1.001-1.010). A
lower baseline serum HBcrAg level was associated with lower
HBV reactivation rates in patients with baseline serum HBsAg
>20 IU/mL (p=0.020, OR 1.034, 95%CI 1.005-1.063) but not
among all patients (p=0.147). 16 (33.3%) patients with HBV
reactivation developed ALT elevation (median ALT 104 U/L,
IQR 62-151 U/L). All HBV reactivation cases were eventually
controlled with either entecavir or tenofovir. Conclusion:
HBV reactivation remained common after treatment cessation
in HBsAg-positive patients with low HBsAg levels. Combining
serum HBsAg and HBcrAg kinetics can identify patients with
likely off-treatment durability after treatment discontinuation.
(Clinicaltrials.gov identifier NCT02738554)

StephenW

417
慢性肝炎的治疗停止
B：通过预测非处理耐久性
病毒标记的组合
Wai Kay Walter Seto1，Kevin Liu2，Lung-Yi Mak3，Ka Shing
Cheung4，Danny Ka Ho Wong5，Fen Liu4，James Fung6，Ching
Lung Lai4和Man-Fung Yuen7，（1）玛丽医院，
香港，香港，（2）医学，玛丽医院，
香港，（3）玛丽医院，（4）医学，
香港大学，（5）肝脏国家重点实验室
研究，香港大学，（6）医学，女王
玛丽医院，（7）香港大学医学系
香港玛丽医院
背景：核苷类似物治疗中的治疗停止
慢性乙型肝炎（CHB）可能与高血压有关
疾病复发率。血清乙型肝炎表面抗原
（HBsAg）水平被认为是反映的标志物
免疫控制。我们调查了治疗效果
停止和预测成功的治疗后耐久性
在血清HBsAg水平低的CHB患者中。方法：我们
前瞻性招募连续非肝硬化HBsAg阳性
接受恩替卡韦或替诺福韦治疗的患者血清
HBsAg <200 IU / mL并履行欧洲协会
肝脏（EASL）治疗停止标准的研究。
肝脏生化，血清HBV DNA，HBsAg和乙型肝炎
在基线测量核心相关抗原（HBcrAg）
治疗停止后每6周至第48周。
HBV再激活定义为HBV DNA> 2,000 IU / mL。
在HBV再激活患者中重新开始治疗
和升高的丙氨酸氨基转移酶（ALT）（> 40 U / L），或
连续两次HBV DNA读数> 2,000 IU / mL（
在两周内进行第二次测量）。结果是
本次中期分析，103例患者（平均年龄56.4±10.9岁，
67.0％男性）平均核苷类似物治疗
招募了7.1（±2.0）年的持续时间。中位数持续时间
治疗停止后的随访时间为42（IQR 29-48）
周。中位基线HBsAg和HBcrAg水平为55.3
（16.9-89.5）IU / mL和1.1（0.3-4.7）kU / mL。该
计算出48周时HBV再激活的累积率
通过Kaplan-Meier方法，为59.2％。 78名患者中
用可用的病毒测量，基线血清HBsAg
与HBsAg> 10 IU / mL相比，≤10IUmL有显着性
较低的HBV再激活累积率（31.6％vs
66.1％，p = 0.023）。通过Cox降低基线血清HBsAg水平
回归，显着降低了
HBV再激活（p = 0.047，OR 1.005,95％CI 1.001-1.010）。一个
较低的基线血清HBcrAg水平与较低水平相关
基线血清HBsAg患者的HBV再激活率
> 20 IU / mL（p = 0.020，OR 1.034,95％CI 1.005-1.063）但不是
在所有患者中（p = 0.147）。 16例（33.3％）HBV患者
再激活发生ALT升高（中位数ALT 104 U / L，
IQR 62-151 U / L）。最终所有HBV再激活病例
用恩替卡韦或替诺福韦控制。结论：
治疗停止后HBV再激活仍然很常见
在HBsAg阳性的HBsAg水平低的患者中。结合
血清HBsAg和HBcrAg动力学可以鉴别患者
治疗中止后可能的治疗后耐久性。
（Clinicaltrials.gov标识符NCT02738554）