慢性乙型肝炎患者血清CC类趋化因子配体5水平与肝纤维化的关系

摘要/Abstract

摘要： 目的探讨慢性乙型肝炎(CHB)患者血清CC类趋化因子配体5(CCL-5)水平与肝纤维化的关系。方法选取2022年6月至2024年6月晋江市医院收治并确诊的180例CHB患者和70名健康体检志愿者(纳入对照组)为研究对象,根据改良Scheuer 评分系统将CHB患者分为非显著肝纤维化组(112例)、显著肝纤维化期组(68例)。收集并比较各组受试者的一般资料[年龄、性别、体质指数、合并基础疾病(高血压、糖尿病、高血脂)、CHB病程(仅限于CHB患者)等]、肝脏超声[肝内结节,测量左肝静脉直径、肝中静脉直径、右肝静脉直径、肝脏硬度测量值(LSM)、门静脉流速]及实验室指标[乙型肝炎病毒脱氧核糖核酸(HBV DNA)、乙型肝炎表面抗原(HBsAg)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、血小板计数、国际标准化比值(INR)、CCL-5]。将非显著肝纤维化组和显著肝纤维化期组单因素分析中存在统计学意义的指标纳入多因素logistic回归分析。采用受试者工作特征(ROC)曲线分析相关指标预测CHB患者显著肝纤维化的价值。结果 3组受试者的性别、体质指数、门静脉流速、ALT、AST、INR比较差异均无统计学意义(P＞0.05),2组CHB组的合并基础疾病、CHB病程、肝内结节比较差异均无统计学意义(P＞0.05)。与对照组相比,2组CHB组的左肝静脉直径、肝中静脉直径、右肝静脉直径、血小板计数均明显减少(P<0.05),LSM、CCL-5均明显增高(P<0.05);与非显著肝纤维化组相比,显著肝纤维化组的左肝静脉直径[(6.62±2.02) mm vs. (5.32±1.52) mm]、肝中静脉直径[(6.79±2.11) mm vs. (5.53±1.60) mm]、右肝静脉直径[(7.55±1.97) mm vs. (5.46±1.38) mm]、血小板计数[(193.26±46.64) ×10⁹/L vs. (171.65±33.57) ×10⁹/L]均明显减少(P<0.05),年龄[(51.2±8.7) 岁 vs. (58.5±9.9) 岁])、LSM[(8.91±2.41) kPa vs. (1.79±2.65) kPa]、HBV DNA[(4.09±1.11) IU/mL vs. (4.62±1.30) IU/mL]、HBsAg[(3.20±0.69) lg U/mL vs. (4.16±1.21) lg U/mL]、CCL-5[(4.62±1.21) ng/mL vs. (5.53±1.60) ng/mL]均明显增高(P<0.05)。Logistic回归分析显示,年龄[OR(95%CI: 1.204 (1.073~1.351)]、LSM[OR(95%CI: 1.754 (1.281~2.402)]、CCL-5[OR(95%CI: 14.737 (5.936~36.589)]均是影响CHB患者显著肝纤维化的危险因素(P<0.05),预测临界值分别为52岁、10.10 kPa、3.58 ng/mL。与单一指标相比,年龄、LSM、CCL-5联合检测的价值较高,曲线下面积(AUC)、灵敏度均较高。结论 CHB伴显著肝纤维化患者血清CCL-5水平显著增高,血清CCL-5是CHB患者肝纤维化的独立危险因素,联合年龄和LSM可显著提高预测CHB患者肝纤维化的效能。

关键词: 慢性乙型肝炎, 趋化因子, CC类趋化因子配体5, 肝纤维化

Abstract: Objective To investigate the relationship between serum C-C motif chemokine ligand 5 (CCL-5) and liver fibrosis in patients with chronic hepatitis B (CHB). Methods A total of 180 CHB patients diagnosed and treated in Jinjiang City Hospital from June 2022 to June 2024 and 70 healthy volunteers served as the control group were enrolled in this study. The CHB patients were divided into a non-significant liver fibrosis group (n=112) and a significant liver fibrosis group (n=68) based on the modified Scheuer scoring system. The general data [age, sex, body mass index, comorbidities (e.g., hypertension, diabetes, hyperlipidemia), CHB duration (only CHB patients)], liver ultrasound findings [e.g., intrahepatic nodules, diameter of the left/middle/right hepatic veins, liver stiffness measurement (LSM), portal vein flow velocity], and laboratory parameters [hepatitis B virus DNA (HBV DNA), hepatitis B surface antigen (HBsAg), alanine aminotransferase (ALT), aspartate aminotransferase (AST), platelet count, international normalized ratio (INR), CCL-5] were collected and compared within the groups. Indicators with statistical significance in univariate analysis between the two CHB groups were included in multivariate Logistic regression analysis. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of relevant indicators for significant liver fibrosis in CHB patients. Results No significant differences were observed among the three groups in sex, body mass index, portal vein flow velocity, ALT, AST and INR (P＞0.05). Between the 2 CHB groups, no significant differences were found in comorbidities, CHB duration and intrahepatic nodules (P＞0.05). Compared with the control group, both CHB groups showed significantly reduced diameters of the left/middle/right hepatic veins and platelet counts (P＜0.05), whereas the LSM and CCL-5 levels were significantly elevated (P＜0.05). Compared with the non-significant fibrosis group, the significant liver fibrosis group showed significantly reduced diameters of the left [(6.62±2.02) mm vs. (5.32±1.52) mm]/middle [(6.79±2.11) mm vs. (5.53±1.60) mm]/right hepatic veins[(7.55±1.97) mm vs. (5.46±1.38) mm] and platelet counts [(193.26±46.64) ×10⁹/L vs. (171.65±33.57) ×10⁹/L] (P＜0.05), whereas the LSM, HBV DNA, HBsAg, and CCL-5 levels were significantly elevated (P＜0.05), and the age [(6.8±2.1)y vs. (58.5±9.9) y]), LSM [(8.91±2.41) kPa vs. (1.79±2.65) kPa], HBV DNA [(4.09±1.11) IU/mL vs. (4.62±1.30) IU/mL], HBsAg [(3.20±0.69) lg U/mL vs. (4.16±1.21) lg U/mL] and CCL-5 [(4.62±1.21) ng/mL vs. (5.53±1.60) ng/mL] were significantly higher (P＜0.05). By Logistic regression analysis it was identified that age [OR(95%CI: 1.204 (1.073~1.351)], LSM[OR(95%CI: 1.754 (1.281~2.402)] and CCL-5 [OR(95%CI: 14.737 (5.936~36.589)] as independent risk factors for significant liver fibrosis in CHB patients (P＜0.05). The optimal cutoff values for predicting significant fibrosis were: age ≥52 years, LSM ≥10.10 kPa and CCL-5 ≥3.58 ng/mL. The combination of these three indicators demonstrated a higher predictive efficacy [area under the curve (AUC) and sensitivity] than that of any single parameter. Conclusion Serum CCL-5 levels are significantly elevated in CHB patients with significant liver fibrosis. CCL-5 is an independent risk factor for liver fibrosis, and its combination with age and LSM significantly improves its diagnostic efficacy as a non-invasive marker for significant liver fibrosis in CHB patients.

Key words: Chronic hepatitis B, Chemokine, C-C motif chemokine ligand 5, Hepatic fibrosis

曾华礼, 施迎迎, 高晓雯, 吕海明. 慢性乙型肝炎患者血清CC类趋化因子配体5水平与肝纤维化的关系[J]. 肝脏, 2026, 31(5): 625-630.

ZENG Hua-li, SHI Ying-ying, GAO Xiao-wen, LV Hai-ming. The relationship between serum C-C motif chemokine ligand 5 and liver fibrosis in chronic hepatitis B patients[J]. Chinese Hepatolgy, 2026, 31(5): 625-630.

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