关键词: 非酒精性脂肪性肝病, 肝纤维化, 趋化因子C-X-C基序配体12, 趋化因子受体4, 趋化因子受体7, 诊断

Abstract: Objective The aim of this study was to investigate the changes and clinical implication of serum levels of chemokine C-X-C motif ligand 12 (CXCL12) and its receptors chemokine receptor 4 (CXCR4) and chemokine receptor 7 (CXCR7) in patients with non-alcoholic fatty liver disease (NAFLD). Method A total of 137 patients with NAFLD were admitted to our hospital between June 2021 and June 2024, and all patients underwent liver biopsy. Liver fibrosis S2 was defined as significant liver fibrosis. Serum CXCL12, CXCR4 and CXCR7, and hyaluronic acid (HA), type III procollagen (PCⅢ), type IV collagen (CⅣ) and laminin (LN) levels were assayed by ELISA. Multivariate Logistic regression model was applied to analyze the related influencing factors of liver fibrosis in patients with NAFLD, and the receiver operating characteristic (ROC) curves were drawn to analyze the predictive efficacy of serum CXCL12, CXCR4, and CXCR7 for liver fibrosis. Result Liver histo-pathological examination found liver fibrosis S0/S1 in 50 cases, S2 in 37 cases, S3 in 34 cases and S4 in 16 cases in our series; serum PCⅢ, CⅣ, LN, HA, CXCL12, CXCR4 and CXCR7 levels in patients with S4 were (135.6±10.7)μg/L,(87.1±8.1)μg/L, (120.3±12.1)μg/L, (107.1±9.8)μg/L, (17.6±2.9)pg/L, (60.2±7.2)pg/mL and (7.5±1.4)ng/L, all significantly higher than [(110.1±13.4)μg/L, (69.2±7.6)μg/L, (99.2±10.8)μg/L, (88.7±10.2)μg/L, (11.5±2.6)pg/L, (45.6±7.5)pg/mL and (4.6±1.0)ng/L, respectively, P＜0.05] in those with S0/S1 or [(117.4±12.8)μg/L, (75.8±8.9)μg/L, (105.3±15.7)μg/L, (93.6±9.1)μg/L, (13.7±2.7)pg/L, (50.7±6.3)pg/mL and (5.5±1.1)ng/L, respectively, P＜0.05] in those with S2 or [(124.5±12.1)μg/L, (81.1±9.1)μg/L, (111.6±13.9)μg/L, (98.8±8.3)μg/L, (15.4±3.0)pg/L, (54.2±8.1)pg/mL and (6.7±1.3)ng/L, respectively, P＜0.05] in those with S3; multivariate Logistic regression analysis showed that serum PCⅢ, CⅣ, LN, HA, CXCL12, CXCR4 and CXCR7 levels were all the independent risk factors for liver fibrosis in patients with NAFLD(P＜0.05); ROC analysis demonstrated that the AUC was 0.896, with sensitivity of 82.76% and specificity of 87.93%, when combination of serum CXCL12, CXCR4 and CXCR7 levels was applied to predict significant liver fibrosis. Conclusion Elevated serum CXCL12, CXCR4 and CXCR7 levels indicate the presence of liver fibrosis in patients with NAFLD, and combination of these three indicators has a high predictive performance for screening liver fibrosis.

Key words: Nonalcoholic fatty liver disease, Liver fibrosis, Chemokine C-X-C motif ligand 12, Chemokine receptor 4, Chemokine receptor 7, Diagnosis