Gastroenterology and Endoscopy United, The Nazareth Hospital, EMMS, Nazareth.
Department of Gastroenterology, Galilee Medical Center, Nahariya.
Eur J Gastroenterol Hepatol. 2019 Sep;31(9):1110-1115. doi: 10.1097/MEG.0000000000001393.
The progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is believed to be the driver for future development of fibrosis and cirrhosis. Nevertheless, there remains a lack of noninvasive methods for the diagnosis of NASH. The aim of the present study was to determine the role of neutrophil-to-lymphocyte ratio (NLR) in predicting histological severity in NAFLD.
We performed a single-center retrospective study in EMMS Nazareth Hospital from July 2014 to May 2017. Liver biopsies were evaluated using the steatosis, activity, and fibrosis scoring system, which includes three components: (i) steatosis (0-3), (ii) activity grade (0-4), and (iii) fibrosis (0-4). Patients were divided into two groups. The first group was considered to have NAFLD when fibrosis grade was 0-1 and inflammatory activity was 0-1, whereas the second group included patients with fibrosis grade of 2-4 and inflammatory activity grade of 2-3, considered to have NASH.
Ninety-one (91) patients with biopsy-proven fatty liver were included. The average age was 42.13 ± 11.5 (18-74) years. Fifty-seven (62.6%) patients were male. Univariate analysis revealed several factors to be associated with advanced fibrosis and inflammatory activity, including NLR, C-reactive protein, and HOMA-IR, which correlated with fibrosis [odds ratio (OR): 1.405, 95% confidence interval (CI): 1.21-1.63, P < 0.0001; OR: 1.329, 95% CI: 1.05-1.68, P = 0.016; and OR: 1.922, 95% CI: 1.18-3.11, P = 0.007, respectively], and NLR, triglycerides, and HOMA-IR, which correlated with hepatocyte inflammation (OR: 1.210, 95% CI: 1.08-1.35, P = 0.0009; OR: 0.984, 95% CI: 0.97-0.99, P = 0.01; and OR: 2.069, 95% CI: 1.28-3.34, P = 0.003, respectively). On multivariate logistic regression analysis, NLR remains independently associated with advanced fibrosis grade and inflammatory activity (OR: 0.734, 95% CI: 0.631-0.854, P < 0.0001, area under the curve: 0.8622 and OR: 0.836, 95% CI: 0.74-0.95, P = 0.006, area under the curve: 0.7845, respectively). Our second major finding was defining an NLR cut-off point that was associated with inflammatory activity and fibrosis grade using receiver operating characteristic analysis based on the Youden index (J), which is defined by the maximal sensitivity and specificity.
NLR showed significant independent correlation with advanced inflammation and fibrosis in patients with NAFLD. This simple available laboratory tool may be incorporated into future diagnostic scores.
非酒精性脂肪性肝病（NAFLD）向非酒精性脂肪性肝炎（NASH）的进展被认为是未来纤维化和肝硬化发展的驱动因素。然而，目前仍然缺乏用于诊断 NASH 的非侵入性方法。本研究旨在确定中性粒细胞与淋巴细胞比值（NLR）在预测 NAFLD 组织学严重程度中的作用。
我们在 2014 年 7 月至 2017 年 5 月期间在 EMMS 拿撒勒医院进行了一项单中心回顾性研究。使用包括三个组成部分的脂肪变性、活动和纤维化评分系统评估肝活检：（i）脂肪变性（0-3），（ii）活动等级（0-4）和（iii）纤维化（0-4）。患者分为两组。第一组被认为是纤维化等级为 0-1 和炎症活动度为 0-1 的 NAFLD，而第二组包括纤维化等级为 2-4 和炎症活动度等级为 2-3 的患者，被认为是 NASH。
共纳入 91 例经活检证实的脂肪肝患者。平均年龄为 42.13±11.5（18-74）岁。57（62.6%）例为男性。单因素分析显示，与晚期纤维化和炎症活动相关的因素包括 NLR、C 反应蛋白和 HOMA-IR，这些因素与纤维化相关[比值比（OR）：1.405，95%置信区间（CI）：1.21-1.63，P<0.0001；OR：1.329，95%CI：1.05-1.68，P=0.016；和 OR：1.922，95%CI：1.18-3.11，P=0.007]，与肝细胞炎症相关的因素包括 NLR、甘油三酯和 HOMA-IR[OR：1.210，95%CI：1.08-1.35，P=0.0009；OR：0.984，95%CI：0.97-0.99，P=0.01；和 OR：2.069，95%CI：1.28-3.34，P=0.003]。多变量逻辑回归分析显示，NLR 与晚期纤维化分级和炎症活动度独立相关（OR：0.734，95%CI：0.631-0.854，P<0.0001，曲线下面积：0.8622；OR：0.836，95%CI：0.74-0.95，P=0.006，曲线下面积：0.7845）。我们的第二个主要发现是使用基于 Youden 指数（J）的接收器工作特征分析（ROC）定义与炎症活动度和纤维化分级相关的 NLR 截断点，J 由最大敏感性和特异性定义。
NLR 与 NAFLD 患者的晚期炎症和纤维化有显著的独立相关性。这种简单的可用实验室工具可能会被纳入未来的诊断评分中。
