The macrophage activation marker sCD163 is associated with morphological disease stages in patients with non-alcoholic fatty liver disease
The macrophage activation marker sCD163 is associated with morphological disease stages in patients with non-alcoholic fatty liver disease
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DOI：
10.1111/liv.13150
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发表时间：
2016-10-01
影响因子：
6.7
通讯作者：
Gronbaek, Henning
中科院分区：
文献类型：
--
作者：
Kazankov, Konstantin;Barrera, Francisco;Gronbaek, Henning
背景与目的巨噬细胞活化在实验性非酒精性脂肪性肝病（NAFLD）中起关键的致病作用，并促进脂肪性肝炎（NASH）和肝纤维化的进展。我们通过测量可溶性CD 163（一种特异性巨噬细胞活化标志物）研究了人类NAFLD中的巨噬细胞活化，假设sCD 163与患者的形态学疾病分级相关。此外，我们研究了sCD 163和细胞凋亡标志物细胞角蛋白-18（CK-18）之间的关系，以探讨巨噬细胞活化和NAFLD之间的联系。MethodsCD 163与NAFLD生化和组织学指标的关系在两个独立的队列中进行了研究，其中157名澳大利亚和174名意大利NAFLD患者，肝活检按NAFLD严重程度、脂肪变性和纤维化分级。结果两组患者sCD 163水平均随病理分级的增加而升高，且与Kleiner纤维化评分独立相关（P < 0.001）。高sCD 163可预测晚期纤维化{F 3;澳大利亚队列：接受者-操作特征曲线下面积0.77 [95%置信区间（CI）：0.76-0.87]，意大利队列：0.80（95% CI：0.72-0.88）}。sCD 163与CK-18独立相关（P < 0.001）。结论sCD 163反映巨噬细胞活化，与NAFLD的形态学特征相关，提示sCD 163参与NAFLD、NASH尤其是纤维化的发病机制。sCD 163和细胞角蛋白-18之间的独立关联表明，细胞凋亡可能有助于NAFLD/NASH中的巨噬细胞活化。
Background & AimsMacrophage activation plays a key pathogenic role in experimental non-alcoholic fatty liver disease (NAFLD) and contributes to the progression of steatohepatitis (NASH) and fibrosis. We studied macrophage activation in human NAFLD by measuring soluble (s)CD163, a specific macrophage activation marker, hypothesizing that sCD163 would be associated with the patients' morphological disease grade. Furthermore, we investigated an association between sCD163 and the apoptosis marker cytokeratin-18 (CK-18) to explore a link between macrophage activation and apoptosis.MethodssCD163 associations with biochemical and histological measures of NAFLD were investigated in two independent cohorts of 157 Australian and 174 Italian NAFLD patients, with liver biopsies graded for NAFLD severity, steatosis and fibrosis. sCD163 and CK-18 were measured by enzyme-linked immunosorbent assay.ResultsIn both cohorts sCD163 increased in parallel with the patients' morphological disease grading, being independently associated with the Kleiner fibrosis score (P < 0.001). A high sCD163 predicted advanced fibrosis {F 3; Australian cohort: area under receiver-operating characteristics curve 0.77 [95% confidence interval (CI): 0.76-0.87], Italian cohort: 0.80 (95% CI: 0.72-0.88)}. In both groups, sCD163 was independently associated with CK-18 (P < 0.001).ConclusionSoluble CD163 reflecting macrophage activation is associated with morphological features of NAFLD suggesting their involvement in the pathogenesis of NAFLD, NASH and particularly fibrosis. An independent association between sCD163 and cytokeratin-18 suggests that apoptosis may contribute to macrophage activation in NAFLD/NASH.