慢性乙型肝炎患者肝硬度测定治疗期间纤维化消退的不可靠

StephenW

Unreliable Estimation of Fibrosis Regression During Treatment by Liver Stiffness Measurement in Patients With Chronic Hepatitis B
Dong Ji  1 , Yan Chen, Qinghua Shang, Huabao Liu, Lin Tan, Jing Wang, Yongping Chen, Qin Li, Qinghua Long, Laicheng Song, Li Jiang, Guangming Xiao, Zujiang Yu, Liang Chen, Xiaoyu Hu, Xiaodong Wang, Da Chen, Zhiqin Li, Zheng Dong, Guofeng Chen, Yongping Yang
Affiliations
Affiliation

    1
    Department of Liver Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; Department of Liver Diseases, the 960th Hospital of Chinese PLA Joint Logistics Support Force, Taian, Shandong Province, China; Traditional Chinese Medicine Hospital of Chongqing, Chongqing, China; Liver Disease Department, Fuyang 2nd People's Hospital, Fuyang, Anhui Province, China; Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan Province, China; Department of Infectious and Liver Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Fuzhou Infectious Diseases Hospital, Fuzhou, Fujian Province, China; Department of Infection and Liver Disease, Yichun People's Hospital, Yichun, Jiangxi Province, China; Traditional Chinese Medicine Hospital of Taihe, Taihe, Anhui Province, China; Department of Infectious Diseases, the First Affiliated Hospital (the Southwest Hospital) of the Third Military Medical University, Chongqing, China; Guangzhou 8th People's Hospital, Guangzhou, Guangdong Province, China; Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China; Department of Hepatic Diseases, Shanghai Public Health Clinical Center, Shanghai, China; Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China.

    PMID: 33840727 DOI: 10.14309/ajg.0000000000001239

Abstract

Introduction: Little reliable evidence has been reported regarding usefulness of liver stiffness measurement (LSM) for monitoring the hepatic fibrosis changes during treatment. We aimed to assess the association between changes in LSM and histological outcomes in patients with chronic hepatitis B.

Methods: In this prospective multicenter study, 727 treatment-naive patients receiving entecavir-based therapy, who underwent paired biopsies at treatment baseline and week 72, were analyzed. Changes in LSM were defined as ≥30% decrease, minor change, and ≥30% increase. Multivariate logistic regression was used to estimate odds ratios (ORs) of changes in LSM on clinical outcomes accounting for regression to the mean. A new on-treatment LSM threshold was established by receiver operating curve.

Results: Overall regression of fibrosis, improvement of inflammation, significant histological response, virologic response, alanine aminotransferase normalization, and hepatitis B e antigen seroconversion were 51.2%, 74.4%, 22.0%, 86.0%, 83.5%, and 13.3%, respectively. The association between changes in LSM and improvement of inflammation was nonlinear (P = 0.012). LSM decrease ≥30% was associated with regression of fibrosis (OR 1.501, 95% confidence interval [CI] 1.073-2.099, P = 0.018), significant histological response (OR 1.726, 95% CI 1.124-2.652, P = 0.013), and alanine aminotransferase normalization (OR 2.149, 95% CI 1.229-3.757, P = 0.007). After adjusting for regression to the mean, LSM increase ≥30% became negatively associated with the above 3 outcomes. A new on-treatment LSM cutoff value of 5.4 kPa was established for indicating the significant histological response.

Discussion: Changes in LSM are unreliable to estimate regression of fibrosis during treatment; the established cutoff value of on-treatment LSM can optimize monitoring strategy for histological outcomes in patients with chronic hepatitis B.

Copyright © The American College of Gastroenterology 2021. All Rights Reserved.

StephenW

慢性乙型肝炎患者肝硬度测定治疗期间纤维化消退的不可靠估计
董吉1，陈欣，尚庆华，刘华宝，林坦，王静，陈永平，李勤，龙庆华，宋来成，李江，肖光明，于江江，陈亮，胡小雨，王晓东，大陈志立李冬董正陈国峰杨永平
隶属关系
联系

    1个
    中国人民解放军总医院第五医疗中心肝病科，北京；中国人民解放军联合后勤保障部队第960医院肝病科，山东泰安；重庆市重庆市中医院；阜阳市第二人民医院肝病科，安徽省阜阳市；西南医科大学附属中医院，四川Lu州；温州医科大学附属第一医院感染与肝病科，浙江温州；福建省福州市福州传染病医院；江西省宜春市宜春市人民医院感染与肝病科；中国安徽省太和市太和市中医院；第三军医大学附属第一医院（西南医院）传染病科；重庆；中国广东省广州市广州市第八人民医院；郑州大学第一附属医院感染科，河南郑州；上海市公共卫生临床中心肝病科，上海；成都中医药大学附属医院传染病科，四川成都

    PMID：33840727 DOI：10.14309 / ajg.0000000000001239

抽象的

简介：鲜有可靠的证据报道肝硬度测量（LSM）可用于监测治疗期间肝纤维化的变化。我们旨在评估慢性乙型肝炎患者的LSM变化与组织学结果之间的关联。

方法：在这项前瞻性多中心研究中，分析了727名接受恩替卡韦为基础治疗的未接受过治疗的患者，他们在治疗基线和第72周接受了配对活检。 LSM的变化定义为减少≥30％，微小变化和增加≥30％。多元逻辑回归用于估计LSM变化在临床结果上的比值比（OR），这说明了回归到均值的原因。通过接收器工作曲线建立了新的治疗中LSM阈值。

结果：纤维化的总体消退，炎症的改善，明显的组织学应答，病毒学应答，丙氨酸氨基转移酶正常化和乙型肝炎e抗原血清转化分别为51.2％，74.4％，22.0％，86.0％，83.5％和13.3％。 LSM改变与炎症改善之间的关联是非线性的（P = 0.012）。 LSM降低≥30％与纤维化消退相关（OR 1.501，95％置信区间[CI] 1.073-2.099，P = 0.018），显着的组织学反应（OR 1.726，95％CI 1.124-2.652，P = 0.013），和丙氨酸氨基转移酶标准化（OR 2.149，95％CI 1.229-3.757，P = 0.007）。在调整为均值回归后，LSM≥30％的增加与上述3个结果呈负相关。建立了新的治疗中LSM临界值5.4 kPa，以表明明显的组织学反应。

讨论：LSM的变化不能可靠地估计治疗期间纤维化的消退；确定的治疗中LSM的临界值可以优化慢性乙型肝炎患者组织学结局的监测策略。

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