优化使用APRI和FIB-4来排除慢性乙型肝炎患者的肝硬化：SONIC-B

StephenW

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

    Milan J Sonneveld, MD
    Willem P Brouwer, MD
    Prof Henry L-Y Chan, MD
    Prof Teerha Piratvisuth, MD
    Prof Ji-Dong Jia, MD
    Prof Stefan Zeuzem, MD
    et al.
    Show all authors

Published:April 08, 2019DOI:https://doi.org/10.1016/S2468-1253(19)30087-1

Summary
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.

StephenW

优化使用APRI和FIB-4来排除慢性乙型肝炎患者的肝硬化：SONIC-B研究的结果

    米兰J Sonneveld，医学博士
    Willem P Brouwer，医学博士
    医学博士Henry L-Y Chan教授
    医学博士Teerha Piratvisuth教授
    贾继东教授，医学博士
    Stefan Zeuzem教授，医学博士
    等。
    显示所有作者

发布时间：2019年4月8日道：htt：//doi.org/10.1016/S2468-1253（19）30087-1

摘要
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。在衍生数据集中应用FIB-4的常规截止值在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。