Poynard Thierry, Munteanu Mona, Charlotte Frederic, Perazzo Hugo, Ngo Yen, Deckmyn Olivier, Pais Raluca, Merrouche Wassil, de Ledinghen Victor, Mathurin Philippe, Ratziu Vlad
Groupe Hospitalier Pitié Salpêtrière APHP, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, Institute of Cardiometabolism and Nutrition (ICAN).
INSERM.
Eur J Gastroenterol Hepatol. 2018 May;30(5):569-577. doi: 10.1097/MEG.0000000000001064.
One of the unmet needs in patients with metabolic risks is the prediction of metabolic liver disease (MLD) by noninvasive tests (NITs).
The primary aim of this study was to construct a new quantitative test for the diagnosis of nonalcoholic steatohepatitis (NASH) using a simplified histological definition.
As a reference, we used a simplified histological definition of NASH derived from the FLIP-CRN-definition that does not require the presence of steatosis and the presence of both lobular inflammation and ballooning. We analyzed 1081 patients from two prospective cohorts at risk of MLD who had biopsies and contemporaneous blood samples. These patients were divided randomly into a training group (n=541) and a control group (n=540) for internal validation. The new test was compared with standard tests, and applied in two large populations at risk of MLD.
Out of 1081 patients with biopsy, 39 (3.6%) cases with significant inflammatory activity or fibrosis (A2orF2) were missed by the current histological definitions. The combination of 11 parameters permitted to construct a test (NIT-NASHs) predicting NASH with an area under the receiver operating characteristic curve (AUROC) of 0.773 (95% confidence interval: 0.730-0.810), confirmed in the control group 0.814 (0.774-0.847). The AUROCs of NIT-NASHs were higher (all P<0.001) than those of ActiTest, FIB4, BARD, and nonalcoholic fatty liver disease scores. A combination of NIT-NASHs with FibroTest (AUROC=0.800; 0.759-0.835) enabled a better prediction (P<0.0001) of significant MLD, A2orF2, than the ActiTest-FibroTest combination.
These results suggested that this new test enables a quantitative assessment of NASH, and when associated with the FibroTest, identifies cases with clinically significant MLD. An external validation is needed.
代谢风险患者尚未满足的需求之一是通过非侵入性检测（NITs）预测代谢性肝病（MLD）。
本研究的主要目的是使用简化的组织学定义构建一种用于诊断非酒精性脂肪性肝炎（NASH）的新定量检测方法。
作为参考，我们使用了源自FLIP-CRN定义的NASH简化组织学定义，该定义不要求存在脂肪变性以及小叶炎症和气球样变同时存在。我们分析了来自两个有MLD风险的前瞻性队列的1081例患者，这些患者均接受了活检并采集了同期血样。这些患者被随机分为训练组（n = 541）和对照组（n = 540）用于内部验证。将新检测方法与标准检测方法进行比较，并应用于两个有MLD风险的大群体。
在1081例接受活检的患者中，当前组织学定义遗漏了39例（3.6%）具有显著炎症活动或纤维化（A2或F2）的病例。11个参数的组合使得能够构建一种检测方法（NIT-NASHs）来预测NASH，其受试者操作特征曲线下面积（AUROC）为0.773（95%置信区间：0.730 - 0.810），在对照组中得到证实为0.814（0.774 - 0.847）。NIT-NASHs的AUROC高于ActiTest、FIB4评分、BARD评分和非酒精性脂肪性肝病评分（所有P < 0.001）。NIT-NASHs与FibroTest组合（AUROC = 0.800；0.759 - 0.835）比ActiTest - FibroTest组合能够更好地预测（P < 0.0001）显著的MLD，即A2或F2。
这些结果表明，这种新检测方法能够对NASH进行定量评估，并且与FibroTest联合使用时，能够识别出具有临床显著意义的MLD病例。需要进行外部验证。
