Neutrophil-to-lymphocyte ratio is independently associated with inflammatory activity and fibrosis grade in nonalcoholic fatty liver disease.

Abstract

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.