肝硬度的早期急剧下降预示了恩替卡韦治疗的慢性乙型肝炎

StephenW

J Viral Hepat. 2019 Jan 9. doi: 10.1111/jvh.13058. [Epub ahead of print]
Early steep decline of liver stiffness predicts histological reversal of fibrosis in chronic hepatitis B patients treated with entecavir.
Kong Y1, Sun Y1, Zhou J1, Wu X1, Chen Y2, Piao H3, Lu L4, Ding H5, Nan Y6, Jiang W7, Xu Y8, Xie W9, Li H10, Feng B11, Shi G12, Chen G13, Li H14, Zheng H15, Cheng J16, Wang T17, Liu H18, Fudong L18, Chen S17, Mao Y19, Sun J20, Chen T21, Han T22, Han Y23, Wang L1, Ou X1, Zhang H24, Jia J1, You H1.
Author information

1
    Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center for Digestive Disease, Beijing, China.
2
    Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
3
    Infectious Disease Department, Affiliated Hospital of Yanbian University, Yanji, Jilin, China.
4
    Department of Gastroenterology and Hepatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
5
    Department of Gastroenterology and Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.
6
    Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
7
    Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China.
8
    Department of Digestive System, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
9
    Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
10
    Liver Cirrhosis Treatment Center, 302 Military Hospital of China, Beijing, China.
11
    Hepatology Institution, Peking University People's Hospital, Beijing, China.
12
    Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
13
    Second Liver Cirrhosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China.
14
    Department of Hepatopancreatobiliary and Splenic Medicine, Affiliated Hospital, Logistics University of People's Armed Police Force, Tianjin, China.
15
    Department of Infectious Disease, the Fifth Hospital of Shijiazhuang City, Shijiazhuang, Hebei, China.
16
    Department of Gastroenterology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
17
    Pathology Department, China-Japan Friendship Hospital, Beijing, China.
18
    Pathology Department, Beijing Youan Hospital, Capital Medical University, Beijing, China.
19
    Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
20
    Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
21
    Department of Infectious Disease, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
22
    Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, China.
23
    Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi, China.
24
    Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.

Abstract

It is unknown whether dynamic changes of liver stiffness measurement (LSM) can predict the reversibility of fibrosis. Therefore, we evaluated the utility of LSM changes in predicting histological changes of fibrosis in patients with chronic hepatitis B (CHB) on antiviral therapy. In a prospective cohort of CHB patients treated with entecavir, virological and biochemical measurement along with LSM were measured at baseline and every 6 months. Liver biopsies were conducted at baseline and month 18 of treatment. Fibrosis regression was defined by two criteria: (1) Ishak score decrease ≥1 stage, (2) Ishak score decrease ≥1 stage or predominantly regressive by posttreatment P-I-R classification. The dynamic changes of LSM and its predictive value for histological reversibility were evaluated with piecewise linear mixed-effects model and ROC analysis. We found that at month 18 of antiviral therapy, liver fibrosis was reserved in 86 of 212 (40.6%) CHB patients by Ishak reversal criterion. Overall, a decline in LSM was associated with attenuation of Ishak score. The rate of LSM decline in the first 6 months was significantly faster in patients with fibrosis reversal (ΔLSM%Ishak =-2.19%/month, p=0.0025; ΔLSM%Ishak/ PIR =-2.56%/month, p=0.0004). The predictive model based on baseline FIB-4 and Ishak score as well as baseline LSM, PLT, ALB and their changes during the first 6 months could predict histological reversal (AUROCI shak =0.74, 95% CI: 0.67-0.80; AUROCI shak/ PIR =0.81, 95% CI: 0.74-0.87). We conclude that in CHB patients changes in LSM during the first 6 months of entecavir therapy can predict histological reversibility of liver fibrosis at month 18 of antiviral therapy. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.
KEYWORDS:

antiviral therapy; chronic hepatitis B; liver fibrosis; liver stiffness measurement; reversibility

PMID:
    30624000
DOI:
    10.1111/jvh.13058

StephenW

J病毒肝病。 2019年1月9日doi：10.1111 / jvh.13058。 [提前打印]
肝硬度的早期急剧下降预示了恩替卡韦治疗的慢性乙型肝炎患者纤维化的组织学逆转。
Kong Y1，Sun Y1，Zhou J1，Wu X1，Chen Y2，Piao H3，Lu L4，Ding H5，Nan Y6，Jiang W7，Xu Y8，Xie W9，Li H10，Feng B11，Shi G12，Chen G13，Li H14 ，Zheng H15，Cheng J16，Wang T17，Liu H18，Fudong L18，Chen S17，Mao Y19，Sun J20，Chen T21，Han T22，Han Y23，Wang L1，Ou X1，Zhang H24，Jia J1，You H1。
作者信息

1
    首都医科大学附属北京友谊医院肝病研究中心，北京市肝硬化转化医学重点实验室，国家消化病临床研究中心，北京，中国。
2
    南方医科大学南方医院感染科，广东广州
3
    延边大学附属医院传染病科，吉林延吉。
4
    上海交通大学医学院附属上海总医院消化内科，上海。
五
    首都医科大学附属北京佑安医院消化内科，肝病科，北京
6
    河北医科大学第三医院中西医结合肝病科，河北石家庄
7
    复旦大学附属中山医院消化内科，上海
8
    首都医科大学附属北京天坛医院消化系，北京
9
    首都医科大学附属北京地坛医院肝病中心，北京
10
    中国军队医院302肝硬化治疗中心，北京，中国。
11
    北京大学人民医院肝病研究所，北京，中国。
12
    复旦大学附属华山医院感染科，上海
13
    中国军队302医院第二肝硬化诊断治疗中心，北京，中国。
14
    中国人民武装警察部队物流大学附属医院肝胆胰脾科，天津
15
    河北省石家庄市第五医院传染病科，河北省石家庄市
16
    复旦大学上海市公共卫生临床中心消化内科，上海
17
    中日友好医院病理科，北京，中国。
18
    首都医科大学附属北京佑安医院病理科，北京
19
    上海交通大学医学院附属仁济医院消化内科，上海
20
    浙江大学医学院邵逸夫医院放射科，浙江杭州
21
    华中科技大学同济医学院附属同济医院传染病研究所传染病科，湖北武汉
22
    天津市第三中心医院消化内科，天津市
23
    第四军医大学西京医院消化内科，山西西安
24
    美国田纳西州孟菲斯市圣犹达儿童研究医院生物统计学系。

抽象

尚不清楚肝脏硬度测量（LSM）的动态变化是否可以预测纤维化的可逆性。因此，我们评估了LSM变化在预测慢性乙型肝炎（CHB）患者抗病毒治疗中纤维化组织学变化方面的效用。在用恩替卡韦治疗的前瞻性CHB患者队列中，在基线和每6个月测量病毒学和生物化学测量以及LSM。在基线和治疗的第18个月进行肝脏活组织检查。纤维化消退由两个标准定义：（1）Ishak评分降低≥1期，（2）Ishak评分降低≥1期或主要通过治疗后P-I-R分类进行回归。采用分段线性混合效应模型和ROC分析评估LSM的动态变化及其组织学可逆性预测值。我们发现，在抗病毒治疗的第18个月，通过Ishak逆转标准，在212名（40.6％）CHB患者中有86名保留了肝纤维化。总的来说，LSM的下降与Ishak评分的减弱有关。纤维化逆转患者前6个月LSM下降速度明显加快（ΔLSM％Ishak = -2.19％/月，p = 0.0025;ΔLSM％Ishak / PIR = -2.56％/月，p = 0.0004）。基于基线FIB-4和Ishak评分以及基线LSM，PLT，ALB及其在前6个月内的变化的预测模型可以预测组织学逆转（AUROCI shak = 0.74,95％CI：0.67-0.80; AUROCI shak / PIR = 0.81,95％CI：0.74-0.87）。
我们得出结论，在CHB患者中，恩替卡韦治疗的前6个月LSM的变化可以预测抗病毒治疗第18个月肝纤维化的组织学可逆性。 本文受版权保护。 版权所有。

本文受版权保护。 版权所有。
关键词：

抗病毒治疗; 慢性乙型肝炎; 肝纤维化; 肝硬度测量;可逆性

结论：
    30624000
DOI：
    10.1111/ jvh.13058