优化使用APRI和FIB-4来排除慢性乙型肝炎患者的肝硬化：来自SO

StephenW

Lancet Gastroenterol Hepatol. 2019 Apr 8. pii: S2468-1253(19)30087-1. doi: 10.1016/S2468-1253(19)30087-1. [Epub ahead of print]
Optimisation of the use of APRI and FIB-4 to rule out cirrhosis in patients with chronic hepatitis B: results from the SONIC-B study.
Sonneveld MJ1, Brouwer WP1, Chan HL2, Piratvisuth T3, Jia JD4, Zeuzem S5, Liaw YF6, Hansen BE7, Choi H8, Wat C9, Pavlovic V9, Gaggar A10, Xie Q11, Buti M12, de Knegt RJ1, Janssen HLA13.
Author information

1
    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
2
    Department of Medicine and Therapeutics and Institute of Digestive Disease, the Chinese University of Hong Kong, Hong Kong SAR, China.
3
    NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand.
4
    Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
5
    Medical Clinic 1, Johann Wolfgang Goethe University Medical Center, Frankfurt, Germany.
6
    Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
7
    Toronto Centre for Liver Disease, University Health Network, Toronto, Canada; IHPME, University of Toronto, Toronto, Canada.
8
    Toronto Centre for Liver Disease, University Health Network, Toronto, Canada.
9
    Roche Products Ltd, Welwyn Garden City, UK.
10
    Gilead Sciences, Foster City, CA, USA.
11
    Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
12
    Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona Liver Unit, Hospital Universitari Vall d'Hebron and CIBEHED del Instituto Carlos III, Barcelona, Spain.
13
    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands; Toronto Centre for Liver Disease, University Health Network, Toronto, Canada. Electronic address: [email protected].

Abstract
BACKGROUND:

Ruling out the presence of cirrhosis is important for the management of chronic hepatitis B. We aimed to study and optimise the performance of two non-invasive indices for ruling out cirrhosis: the aspartate aminotransferase-platelet ratio index (APRI) and fibrosis score based on four factors (FIB-4).
METHODS:

We applied established cutoffs to rule in (APRI >2·00; FIB-4 >3·25) or rule out (APRI <1·00; FIB-4 <1·45) cirrhosis to data from eight global randomised trials that required baseline biopsy, and identified new cutoffs aiming for a sensitivity for detection of cirrhosis greater than 90% and a negative predictive value (NPV) of greater than 95% in the same dataset. We externally validated the new cutoffs using data from all consecutive biopsied patients from two tertiary referral hospitals in the Netherlands and Canada.
FINDINGS:

In the derivation dataset (n=2926; of whom 1750 were Asian); 340 (12%) individuals had cirrhosis. The validation cohort consisted of 1034 individuals (of whom 575 were Asian), with 155 (15%) individuals with cirrhosis. Application of conventional cutoffs for FIB-4 in the derivation dataset yielded unclassifiable results in 686 (23%) individuals, and 139 (41%) of the 340 patients with cirrhosis were misclassified as having no cirrhosis. Similarly, conventional cutoffs for APRI in the derivation dataset yielded unclassifiable results in 706 (24%) individuals, and 153 (45%) were misclassified as having no cirrhosis. An APRI of 0·45 or less had sensitivity of 91·5%, an NPV of 95·4%, and misclassified 29 (9%) of 340 individuals with cirrhosis in the derivation dataset, but performance was reduced in the validation set (22 [14%] of 155 individuals with cirrhosis misclassified). A FIB-4 score of 0·70 had a sensitivity of 90·9%, an NPV of 96·6%, and misclassified 31 (9%) of individuals with cirrhosis in the derivation dataset. In the validation cohort, the same score gave a sensitivity of 94·2%, an NPV of 97·3%, and misclassified nine (6%) of the individuals with cirrhosis. Subgroup analysis indicated that the new FIB-4 cutoff performed acceptably in all subgroups except for individuals aged 30 years or younger.
INTERPRETATION:

Conventional cutoffs for APRI and FIB-4 should not be used to guide management of patients with chronic hepatitis B due to high rates of misclassification. A newly identified and externally validated cutoff for FIB-4 (≤0·70) can be used to exclude cirrhosis in patients over 30 years of age.
FUNDING:

Foundation for Liver and Gastrointestinal Research, Rotterdam, Netherlands.

Copyright © 2019 Elsevier Ltd. All rights reserved.

PMID:
    30975477
DOI:
    10.1016/S2468-1253(19)30087-1

StephenW

柳叶刀Gastroenterol Hepatol。 2019年4月8日.pii：S2468-1253（19）30087-1。 doi：10.1016 / S2468-1253（19）30087-1。 [印刷前的电子版]
优化使用APRI和FIB-4来排除慢性乙型肝炎患者的肝硬化：来自SONIC-B研究的结果。
Sonneveld MJ1，Brouwer WP1，Chan HL2，Piratvisuth T3，Jia JD4，Zeuzem S5，Liaw YF6，Hansen BE7，Choi H8，Wat C9，Pavlovic V9，Gaggar A10，Xie Q11，Buti M12，de Knegt RJ1，Janssen HLA13。
作者信息

1
    荷兰鹿特丹伊拉斯谟MC大学医学中心消化内科和肝病学系。
2
    香港中文大学医学与治疗学系和消化疾病研究所，中国香港特别行政区。
3
    NKC Songklanagarind医院消化内科和肝脏病学研究所，Songkla大学王子，泰国合艾。
4
    首都医科大学附属北京友谊医院肝脏研究中心，中国北京。
五
    医疗诊所1，Johann Wolfgang歌德大学医学中心，德国法兰克福。
6
    台湾台北长庚大学医学院长庚纪念医院肝脏研究室
7
    加拿大多伦多大学健康网多伦多肝病中心; IHPME，加拿大多伦多多伦多大学。
8
    加拿大多伦多大学健康网多伦多肝病中心。
9
    罗氏产品有限公司，英国韦林花园城。
10
    吉利德科学，福斯特城，加利福尼亚州，美国。
11
    上海交通大学医学院附属瑞金医院感染科，上海
12
    西班牙巴塞罗那瓦尔德希伯伦大学医院和巴勒斯坦大学医学院内科医学系肝脏科，西班牙巴塞罗那卡尔斯三世大学
13
    荷兰鹿特丹Erasmus MC大学医学中心胃肠病学和肝病学系;加拿大多伦多大学健康网多伦多肝病中心。电子地址：[email protected]。

抽象
背景：

排除肝硬化的存在对于慢性乙型肝炎的治疗非常重要。我们的目的是研究和优化两种非侵入性指数排除肝硬化的表现：天冬氨酸氨基转移酶 - 血小板比值指数（APRI）和纤维化评分基于四个因素（FIB-4）。
方法：

我们应用确定的截止值来治疗（APRI> 2·00; FIB-4> 3·25）或排除（APRI <1 00; FIB-4 <1·45）肝硬化，来自8项全球随机试验的数据基线活组织检查，并确定新的临界值，目的是在同一数据集中检测肝硬化的灵敏度大于90％，阴性预测值（NPV）大于95％。我们使用来自荷兰和加拿大两家三级转诊医院的所有连续活检患者的数据，在外部验证了新的临界值。
发现：

在推导数据集中（n = 2926;其中1750是亚洲人）; 340名（12％）人患有肝硬化。验证队列包括1034名个体（其中575名是亚洲人），155名（15％）患有肝硬化。 FIB-4的常规截止值在衍生数据集中的应用在686（23％）个体中产生了不可分类的结果，并且340个肝硬化患者中的139个（41％）被错误分类为没有肝硬化。类似地，衍生数据集中APRI的常规截止值在706（24％）个体中产生了不可分类的结果，153个（45％）被错误分类为没有肝硬化。在推导数据集中，APR为0.45或更低的敏感性为91.5％，NPV为95.4％，并且340个肝硬化患者中29个（9％）被错误分类，但验证集中的性能降低（ 155例肝硬化患者中有22例[14％]错误分类）。在衍生数据集中，FIB-4评分为0.70，灵敏度为90·9％，NPV为96·6％，错误分类为31例（9％）肝硬化患者。在验证队列中，相同评分的敏感性为94·2％，NPV为97.3％，错误分类为9例（6％）肝硬化患者。亚组分析表明，新的FIB-4截止值在所有亚组中均可接受，但30岁或以下的个体除外。
解释：

APRI和FIB-4的常规临界值不应用于指导慢性乙型肝炎患者的管理，因为误分类率很高。 FIB-4（≤0·70）的新鉴定和外部验证截止值可用于排除30岁以上患者的肝硬化。
资金：

荷兰鹿特丹肝脏和胃肠研究基金会。

版权所有©2019 Elsevier Ltd.保留所有权利。

结论：
    30975477
DOI：
    10.1016 / S2468-1253（19）30087-1