FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study
FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study
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DOI：
10.1016/s2468-1253(19)30383-8
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发表时间：
2020-04-01
影响因子：
35.7
通讯作者：
Harrison, Stephen A.
中科院分区：
文献类型：
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作者：
Newsome, Philip N.;Sasso, Magali;Harrison, Stephen A.
背景：全球范围内，非酒精性脂肪性肝病（NAFLD）的负担正在增加，一个主要的优先事项是识别有更大进展为肝硬化风险的非酒精性脂肪性肝炎（NASH）患者，这些患者将成为临床试验和新兴药物治疗的候选者。我们的目标是建立一个评分来识别NASH、NAFLD活动评分升高（NAS >= 4）和晚期纤维化（2期或更高[F >= 2]）的患者。方法本前瞻性研究在多个国际队列验证之前包括一个衍生队列。衍生队列是一项横断面、多中心研究，研究对象为年龄在18岁或以上的患者，这些患者计划在英格兰的7个三级肝脏护理中心接受疑似NAFLD的肝活检。这是一项主要终点已经报道的研究中预先指定的次要终点。采用振动控制瞬态弹性仪测量肝脏刚度（LSM）和纤维扫描仪测量控制衰减参数（CAP），并结合天冬氨酸转氨酶（AST）、丙氨酸转氨酶（All）或AST:ALT比值。为了识别NASH、NAS升高和显著纤维化患者，确定了最佳拟合的多变量logistic回归模型，并使用bootstrap进行了内部验证。在英国的衍生数据集和7个独立的国际（法国、美国、中国、马来西亚、土耳其）经组织学证实的NAFLD患者队列（外部验证队列）中确定评分校准和区分性能。本研究已在ClinicalTrials.gov注册，编号NCT01985009。在2014年3月20日至2017年1月17日期间，在英国肝脏诊所就诊的350例疑似NAFLD患者被前瞻性纳入衍生队列。结合LSM、CAP和AST的预测效果最好的模型被命名为FAST （FibroScan-AST）。衍生数据集的性能令人满意（c -统计量0.80,95% CI 0.76-0.85），并且校准良好。在外部验证队列中，评分的校正是令人满意的，并且在整个验证队列中具有良好的辨别性（c统计量范围为0.74- 0.95,0.85；在合并的外部验证患者队列中，95% CI为0.83-0.87;n=1026）。在衍生队列中，敏感性为0.90及以上的临界值为0.35，特异性为0.90及以上的临界值为0.67，阳性预测值（PPV）为0.83(84/101)，阴性预测值（NPV）为0.85（93/110）。在外部验证队列中，PPV范围为0.33至0.81，NPV范围为0.73至1.0。FAST评分为临床试验或治疗提供了一种有效的非侵入性识别进展性NASH风险患者的方法，从而减少了不太可能有重大疾病的患者不必要的肝活检。版权所有(C) 2020作者。Elsevier Ltd.出版。
Background The burden of non-alcoholic fatty liver disease (NAFLD) is increasing globally, and a major priority is to identify patients with non-alcoholic steatohepatitis (NASH) who are at greater risk of progression to cirrhosis, and who will be candidates for clinical trials and emerging new pharmacotherapies. We aimed to develop a score to identify patients with NASH, elevated NAFLD activity score (NAS >= 4), and advanced fibrosis (stage 2 or higher [F >= 2]).Methods This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (All), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov , number NCT01985009.Findings Between March 20,2014, and Jan 17,2017,350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0.80, 95% CI 0.76-0.85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0.74-0 .95,0.85; 95% CI 0.83-0.87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0.35 for sensitivity of 0.90 or greater and 0.67 for specificity of 0.90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0.83 (84/101) and a negative predictive value (NPV) of 0.85 (93/110). In the external validation cohorts, PPV ranged from 0.33 to 0.81 and NPV from 0.73 to 1.0.Interpretation The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.