Zhao Su-Xian, Li Wen-Cong, Fu Na, Kong Ling-Bo, Zhang Qing-Shan, Han Fang, Ren Wei-Guang, Cui Po, Du Jing-Hua, Wang Bao-Yu, Zhang Yu-Guo, Wang Rong-Qi, Kong Li, Nan Yue-Min
Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
Exp Ther Med. 2020 Dec;20(6):228. doi: 10.3892/etm.2020.9358. Epub 2020 Oct 15.
Hepatic fibrosis is a crucial pathological process involved in the development of chronic hepatitis C (CHC) and may progress to liver cirrhosis and hepatocellular carcinoma. Activated peripheral blood monocytes and intrahepatic macrophages further promote hepatic fibrogenesis by releasing proinflammatory and profibrogenic cytokines. The present study aimed to investigate the role of peripheral CD14 monocytes and intrahepatic CD163 macrophages in hepatitis C virus (HCV)-associated liver fibrosis and clarify whether serum soluble CD163 (sCD163) may serve as a fibrosis marker in patients with CHC. A total of 87 patients with CHC and 20 healthy controls were recruited. Serum sCD163 levels were measured by ELISA. Frequencies of peripheral CD14 monocytes and inflammatory cytokines expressed by CD14 monocytes were analyzed by flow cytometry. The degree of fibrosis in human liver biopsies was graded using the Metavir scoring system and patients were stratified into two groups based on those results (F<2 vs. F≥2). Hepatic expression of CD163 was examined by immunohistochemical staining. The diagnostic values of sCD163, aspartate aminotransferase to platelet ratio index (APRI), fibrosis 4 score (FIB-4) and the aspartate aminotransferase to alanine aminotransferase ratio (AAR) in significant fibrosis (F≥2) were evaluated and compared using receiver operating characteristic (ROC) curves. The results indicated that the serum sCD163 levels and the frequency of CD14 monocytes were significantly higher in the patients than that in the controls and positively correlated with liver fibrosis. The level of serum sCD163 was consistent with hepatic CD163 expression in the liver sections from patients. The frequencies of interleukin (IL)-8- and tumor necrosis factor-α-expressing monocytes were increased and that of IL-10-expressing monocytes was decreased in the patients. The area under the ROC curve (AUROC) for sCD163, APRI, FIB-4 and AAR was 0.876, 0.785, 0.825 and 0.488, respectively, and the AUROC for sCD163 was significantly higher than those for APRI and AAR. In conclusion, sCD163 may serve as a novel marker for assessing the degree of liver fibrosis in HCV-infected patients.
肝纤维化是慢性丙型肝炎(CHC)发展过程中的一个关键病理过程,可能进展为肝硬化和肝细胞癌。活化的外周血单核细胞和肝内巨噬细胞通过释放促炎和促纤维化细胞因子进一步促进肝纤维化的形成。本研究旨在探讨外周血CD14单核细胞和肝内CD163巨噬细胞在丙型肝炎病毒(HCV)相关肝纤维化中的作用,并阐明血清可溶性CD163(sCD163)是否可作为CHC患者的纤维化标志物。共招募了87例CHC患者和20名健康对照者。采用酶联免疫吸附测定法(ELISA)检测血清sCD163水平。通过流式细胞术分析外周血CD14单核细胞的频率以及CD14单核细胞表达的炎性细胞因子。使用梅塔维(Metavir)评分系统对人肝活检组织的纤维化程度进行分级,并根据结果将患者分为两组(F<2与F≥2)。通过免疫组织化学染色检测肝组织中CD163的表达。使用受试者工作特征(ROC)曲线评估并比较sCD163、天冬氨酸氨基转移酶与血小板比值指数(APRI)、纤维化4评分(FIB-4)以及天冬氨酸氨基转移酶与丙氨酸氨基转移酶比值(AAR)在显著纤维化(F≥2)中的诊断价值。结果表明,患者血清sCD163水平和CD14单核细胞频率显著高于对照组,且与肝纤维化呈正相关。患者肝脏切片中血清sCD163水平与肝组织中CD163表达一致。患者中表达白细胞介素(IL)-8和肿瘤坏死因子-α的单核细胞频率增加,而表达IL-10的单核细胞频率降低。sCD163、APRI、FIB-4和AAR的ROC曲线下面积(AUROC)分别为0.876、0.785、0.825和0.488,sCD163的AUROC显著高于APRI和AAR。总之,sCD163可能作为评估HCV感染患者肝纤维化程度的一种新型标志物。