2016年EASL：五年期 - 治疗系统地监测的 肝脏硬度测量

StephenW

GS02
FIVE-YEAR ON-TREATMENT SYSTEMATICALLY MONITORING OF
DYNAMIC CHANGES OF LIVER STIFFNESS MEASUREMENT WITH
TRANSIENT ELASTOGRAPHY COMPARED WITH PAIRED LIVER
BIOPSIES IN A RANDOMIZED CONTROLLED TRIAL IN CHRONIC
HEPATITIS B PATIENTS
J. Sun1, Q. Xie2, D. Tan3, Q. Ning4, J. Niu5, X. Bai6, R. Fan1, X. Liang1,
S. Chen7, J. Cheng8, Y. Yu9, H. Wang10, M. Xu11, G. Shi12, M.Wan13,
X. Chen14, H. Tang15, J. Sheng16, X. Dou17, J. Shi18, H. Ren19, M.Wang20,
H. Zhang21, Z. Gao22, C. Chen23, H. Ma24, Y. Chen1, J. Jia24, J. Hou1.
1Hepatology Unit, Nanfang Hospital, Southern Medical University,
Guangzhou; 2Department of Infectious Diseases, Ruijin Hospital,
Shanghai; 3Department of Infectious Diseases, Xiangya Hospital,
Changsha; 4Department of Infectious Diseases, Tongji Hospital, Wuhan;
5Hepatology Unit, No.1 Hospital affiliated to Jilin University, Changchun;
6Department of Infectious Diseases, Tangdu Hospital, Xi’an; 7Ji’nan
Infectious Diseases Hospital, Ji’nan; 8Beijing Ditan Hospital;
9Department of Infectious Diseases, First Hospital of Peking University;
10Hepatology Unit, Peking University People’s Hospital, Beijing;
118th People’s Hospital, Guangzhou; 12Department of Infectious Diseases,
Huashan Hospital; 13Department of Infectious Diseases, Changhai
Hospital, Shanghai; 14Beijing Youan Hospital, Beijing; 15Department of
Infectious Diseases, Huaxi Hospital, Chengdu; 16Department of
Infectious Diseases, Zhejiang University 1st Affiliated Hospital,
Hangzhou; 17Department of Infectious Diseases, Shengjing Hospital,
Shenyang; 186th People’s Hospital, Hangzhou; 19Department of
Infectious Diseases, Chongqing Medical University 2nd Affiliated
Hospital, Chongqing; 20Department of Infectious Diseases, 81st PLA
Hospital, Nanjing; 21302nd PLA Hospital, Beijing; 22Department of
Infectious Diseases, Sun Yat-Sen University 3rd Affiliated Hospital,
Guangzhou; 23Department of Infectious Diseases, 85th PLA Hospital,
Shanghai; 24Hepatology Unit, Beijing Friendship Hospital, Beijing, China
E-mail: [email protected]
Background and Aims: Transient elastography is a rapid, noninvasive
and reproducible method to measure liver stiffness. Liver
stiffness measurement (LSM) has been shown to be a reliable tool
to diagnose advanced fibrosis or liver cirrhosis in chronic hepatitis B
(CHB). However, the use of LSM to monitor liver fibrosis dynamics
has not been thoroughly evaluated during antiviral therapy.
Methods: Six hundred and six patients with HBV DNA ≥5 Log10
copies/mL, ALT 2–10 × ULN and compensated adult naive HBeAgpositive
CHB were enrolled in a multicenter, randomized controlled
trial (EFFORT Study; Sun J, et al. Hepatology. 2014; Fan R, et al. Gut.
2015), receiving telbivudine (LDT) alone or combined with adefovir
(ADV) for up to 260 weeks (5 years). LSM was performed using
transient elastography (FibroScan®, Echosens, France) at the interval
of 24weeks during the 5-year antiviral treatment. Percutaneous liver
biopsy was performed at baseline and week 104.
Results: Five hundred and ninety-nine of intent-to-treat population
were enrolled in the analysis, among which 347 patients with
qualified paired biopsies. During 5-year antiviral treatment, LSM
decreased rapidly from 8.5 (2.6–49.5) kPa at baseline to 6.1 (2.2–37.4)
kPa at week 24, and then decreased slowly from 6.1 (2.2–37.4) kPa at
week 24–4.9 (2.3–19.6) kPa at week 260. From baseline toweek 104,
liver biopsy evaluation showed that the proportion of patients with
no or mild necroinflammation (Knodell range 0–3) increased from
29.7% (103/347) to 77.2% (268/347), and the proportion of patients
with no or mild fibrosis (Ishak range 0–2) increased from 29.1%
(101/347) to 66.0% (229/347). At baseline, the AUROC of LSM for
patients with advanced fibrosis (Ishak >2) was 0.816. Multivariate
logistic regression analysis showed that values of 24-week and 52-
week LSM were independently associated with 104-week liver
necroinflammation (Knodell ≤2; OR, 1.889; p = 0.014) and fibrosis
(Ishak ≤2; OR, 3.002; p = 0.023), respectively.
Conclusions: The kinetics of LSM decreased during long-term
antiviral therapy with bi-phase pattern, which may mainly reflect
the resolution of inflammation during the first phase, and the
regression of fibrosis during the second phase. Transient elastography
is a useful tool for the evaluation of the change of liver inflammation
and fibrosis during antiviral therapy.

StephenW

GS02
五年期-治疗系统地监测的
肝脏硬度测量，带动态变化
瞬时弹性成像比较了PAIRED肝
活检的随机对照试验慢性
乙肝患者
J. Sun1，问：Xie2，D Tan3，问：Ning4，J. Niu5，十Bai6，R.风扇1，X.亮1，
S. Chen7，J. Cheng8，Y. Yu9，H Wang10，M. Xu11，G Shi12，M.Wan13，
十Chen14，H Tang15，J. Sheng16，X. Dou17，J. Shi18，H Ren19，M.Wang20，
H. Zhang21，Z. Gao22，C Chen23，H Ma24，Y.臣1，J Jia24，J. Hou1。
1Hepatology单位，南方医科大学南方医院，南方医科大学，
广州;传染病教研室，瑞金医院，
上海;传染病3Department，湘雅医院，
长沙;传染病，同济医院，武汉4Department;
5Hepatology单位，第一附属医院吉林长春;
传染病，唐都医院，西安6Department; 7Ji'nan
传染病医院，济南; 8Beijing地坛医院;
传染病9Department，北京大学第一医院;
10肝病单位，北京大学人民医院，北京;
118人民医院，广州;传染病12Department，
华山医院;传染病13Department，长海
医院，上海; 14Beijing佑安医院，北京;的15Department
传染病，华西医院，成都;的16Department
传染病，浙江大学附属第一医院，
杭州;传染病17Department，盛京医院，
沉阳; 186人民医院，杭州;的19Department
传染病，重庆医科大学附属第二
医院，重庆;传染病20Department，解放军第81
医院，南京;第二万一千三百零二解放军医院，北京;的22Department
传染病，孙中山大学第三附属医院，
广州;传染病23Department，解放军第85医院，
上海; 24Hepatology单位，北京友谊医院，北京，中国
电子信箱：[email protected]
背景和目的：瞬时弹性是一种快速，无创
和可重复的方法来测量肝脏硬度。肝
刚度测量（LSM）已被证明是一个可靠的工具
诊断慢性乙型肝炎肝纤维化或肝硬化
（CHB）。然而，使用LSM的监控肝纤维化动力学
一直没有抗病毒治疗过程中彻底评估。
方法：六零六例HBV DNA≥5LOG10
拷贝/ ml，ALT 2-10×ULN和补偿成人幼稚HBeAg阳性
CHB多中心患者，随机对照
试验（努力学习;孙健等肝病2014年;范R等人肠。
2015年），替比夫定接收（LDT）单独或与阿德福韦联合
（ADV）长达260周（5年）。 LSM使用进行
在间隔瞬时弹性成像（FibroScan®，Echosens，法国）
的5年抗病毒治疗过程中24周。经皮肝
活检在基线和周104执行。
结果：5百99意向性治疗人群的
在分析患者，其中347例
合格的配对活检。在5年的抗病毒治疗，LSM
迅速下降为8.5（2.6-49.5）千帕在基线至6.1（2.2-37.4）
帕在24周，然后再慢慢地从6.1（2.2-37.4）千帕在下降
周24-4.9（2.3-19.6）在千帕每周260从基线toweek 104，
肝活检评价结果表明，患者的比例与
无或轻度炎症坏死（科诺德范围0-3）从增加的
29.7％（三百四十七分之一百〇三）为77.2％（347分之268），以及患者的比例
无或轻度纤维化（伊沙克范围0-2）从29.1％上升
（三百四十七分之一百〇一）为66.0％（347分之229）。在基线，LSM的AUROC为
患者晚期肝纤维化（伊沙克> 2）为0.816。多元
Logistic回归分析显示，24周和52-值
周LSM独立与104周的肝脏相关
坏死性炎症（柯诺戴尔≤2; OR，1.889; P = 0.014）和纤维化
（≤2伊沙克;或者3.002，P = 0.023），分别为。
结论：LSM的动力学长期下降过程中
抗病毒治疗与双相图案，这可能主要反映
炎症在第一阶段的分辨率，并且
在第二阶段期间纤维化消退。瞬时弹性
为肝脏炎症的变化的评价的有用工具
和抗病毒治疗期间纤维化。