AASLD2016[610]急性乙型肝炎的免疫反应：慢性对 解决了HBV感染

StephenW

610
Immune Responses in Acute Hepatitis B: Chronicity versus
Resolved HBV Infection.
Femke Stelma1,2, Annikki de Niet1,2, Sophie Willemse1,2, Marjan
J. Sinnige2, Hans L. Zaaijer3, Ester M. van Leeuwen2, Neeltje A.
Kootstra2, Hendrik W. Reesink1,2; 1Department of Gastroenterology
and Hepatology, Academic Medical Center, Amsterdam,
Netherlands; 2Department of Experimental Immunology, Academic
Medical Center, Amsterdam, Netherlands; 3Department of Virology,
Academic Medical Center, Amsterdam, Netherlands

Background and aims The majority of adult patients who
acquire hepatitis B virus (HBV) infection will spontaneously clear
the virus. However, some patients become chronically infected
and the mechanism that leads to chronicity is largely unknown.
Here we analysed the early dynamics of natural killer (NK)
and HBV-specific T cells during acute HBV infection in patients
who cleared HBV as well as a unique patient who did not clear
HBV and became chronically infected. Methods We included
9 patients with acute HBV infection (genotype A n=5, genotype
B, D, E and F all n=1). Patients were assessed at baseline (BL),
week 1, 4, 12 and 24. Eight healthy controls were included
for comparison. NK cell characteristics were analysed by flowcytometry.
PBMC from patients infected with genotype A were
stimulated in vitro with HBV peptide pools, followed by intracellular
cytokine staining. Results At BL, median HBV DNA
load was 5.12 log IU/mL (range 3.53-8.23) and median was
ALT 2,652 U/mL (range 690-3,970). Of 9 patients, 8 cleared
HBsAg within 6 months (6/8 with anti-HBs formation) and one
patient (genotype A) became chronically infected (i.e. meeting
the criteria of HBsAg and HBV DNA positivity ≥ 6 months
after infection). Early time points after infection were associated
with an increase in CD56bright NK cells (median 7.4%)
as compared to healthy controls (median 1.4%, p=0.0037)
and increased expression of CD38, HLA-DR, NKp46, perforin
and granzyme B. Similarly, TRAIL expression on CD56bright
NK cells was upregulated (median 11.7% at BL compared to
1.9% in healthy controls p=0.0025) and decreased towards
week 24. At week 24 TRAIL expression in patients who cleared
HBV was 4.7% (range 2.8—10.3) whereas in the chronically
infected patients TRAIL expression did not decrease (25.5% at
week 24). In patients that cleared HBV, the peak of HBV-specific
CD8+ and CD4+ responses was generally seen later in
the course of the infection (around week 1 or 4). In the patient
that became chronically infected, very low HBV-specific T cell
responses were observed at all time points. Conclusion NK
cells are activated early in the course of acute HBV infection.
In patients who clear acute HBV infection, broad and multi-specific
T cell responses are observed. As exemplified by one
patient who did not clear HBV infection, failure of NK cell
normalization as well as narrow T cell responses may lead to
chronic infection.
Disclosures:
Hendrik W. Reesink - Consulting: Abbvie, Alnylam, BMS, Gilead, Janssen-Cilag,
Merck, PRA-International, Regulus, Boehringer Ingelheim, Roche, R-Pharm;
Grant/Research Support: AbbVie, BMS, Boehringer Ingelheim, Gilead, Janssen-
Cilag, Merck, PRA-International, Regulus, Replicor, Roche
The following people have nothing to disclose: Femke Stelma, Annikki de Niet,
Sophie Willemse, Marjan J. Sinnige, Hans L. Zaaijer, Ester M. van Leeuwen,
Neeltje A. Kootstra

StephenW

AASLD2016 [610]急性乙型肝炎的免疫反应：慢性对
解决了HBV感染。
急性乙型肝炎的免疫反应：慢性对
解决了HBV感染。
Femke Stelma1,2，Annikki de Niet1,2，Sophie Willemse1,2，Marjan
J. Sinnige2，Hans L.Zaaijer3，Ester M.van Leeuwen2，Neeltje A.
Kootstra2，Hendrik W. Reesink1,2;消化内科
和Hepatology，Academic Medical Center，Amsterdam，
荷兰;实验免疫学
医疗中心，荷兰阿姆斯特丹;病毒学，
学术医疗中心，荷兰阿姆斯特丹

背景和目的大多数成年患者
获得乙型肝炎病毒（HBV）感染会自发清除
病毒。然而，一些患者变成慢性感染
并且导致慢性的机制在很大程度上是未知的。
在这里我们分析了自然杀伤（NK）
和HBV特异性T细胞在急性HBV感染患者
谁清除HBV以及一个独特的病人谁没有清除
HBV并成为慢性感染。方法我们包括
9例急性HBV感染患者（基因型A n = 5，基因型
B，D，E和F全部n = 1）。在基线（BL）评估患者，
第1周，第4周，第12周和第24周。包括8个健康对照
用于比较。通过流式细胞术分析NK细胞特征。
来自感染基因型A的患者的PBMC
用HBV肽库体外刺激，然后进行细胞内刺激
细胞因子染色。结果在BL，中位数HBV DNA
负荷为5.12logIU / mL（范围3.53-8.23），中位数为
ALT 2,652U / mL（范围690-3,970）。 9例患者，8例清除
HBsAg在6个月内（6/8与抗HBs形成）和一个
患者（基因型A）成为慢性感染（即会议）
HBsAg和HBV DNA阳性标准≥6个月
感染后）。感染后的早期时间点相关
与CD56bright NK细胞增加（中值7.4％）
（中位数为1.4％，p = 0.0037）
和CD38，HLA-DR，NKp46，穿孔素的表达增加
和颗粒酶B.类似地，在CD56bright上的TRAIL表达
NK细胞上调（与BL相比中位数为11.7％
1.9％在健康对照中p = 0.0025），并向下降
24周。在24周TRAIL表达在清除的患者中
HBV为4.7％（范围2.8-10.3），而在慢性
感染患者TRAIL表达没有降低（25.5％
第24周）。在清除HBV的患者中，HBV特异性的峰值
CD8 +和CD4 +反应一般见于后面
感染的过程（大约1周或4周）。在病人
成为慢性感染，非常低的HBV特异性T细胞
在所有时间点观察到反应。结论NK
细胞在急性HBV感染过程中早期被激活。
在清除急性HBV感染的患者中，广泛和多特异性
观察到T细胞应答。例如一个
患者没有清除HBV感染，NK细胞衰竭
正常化以及窄T细胞应答可能导致
慢性感染。
披露：
Hendrik W. Reesink - 咨询：Abbvie，Alnylam，BMS，Gilead，Janssen-Cilag，
Merck，PRA-International，Regulus，Boehringer Ingelheim，Roche，R-Pharm;
资助/研究支持：AbbVie，BMS，Boehringer Ingelheim，Gilead，Janssen-
Cilag，Merck，PRA-International，Regulus，Replicor，Roche
下面的人没有什么可以披露：Femke Stelma，Annikki de Niet，
Sophie Willemse，Marjan J. Sinnige，Hans L.Zaaijer，Ester M.van Leeuwen，
Neeltje A. Kootstra

四十己过

把一些垃圾文章顶到第二页面去，版主跑哪去了？