Department of Hepatology & Gastroenterology, and European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Aarhus University Hospital, Aarhus, Denmark.
Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, and European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Oslo University Hospital Rikshospitalet, Oslo, Norway.
Clin Transl Gastroenterol. 2021 Mar 1;12(3):e00315. doi: 10.14309/ctg.0000000000000315.
Primary sclerosing cholangitis (PSC) is a progressive liver disease characterized by bile duct inflammation and fibrosis. The role of macrophages in PSC development and progression is less studied. Macrophage activation markers soluble (s)CD163 and mannose receptor (sMR) are associated with disease severity and outcome in other liver diseases, but not previously investigated in PSC. We evaluated sCD163 and sMR regarding disease severity and prognosis in patients with PSC.
We investigated 2 independent PSC cohorts from Oslo (n = 138) and Helsinki (n = 159) and analyzed blood sCD163 and sMR levels. The Mayo score, Enhanced Liver Fibrosis Test, and Amsterdam-Oxford model were assessed for comparison.
Median (interquartile range) sCD163 was 3.32 (2.27-5.60) and 1.96 (1.47-2.70) mg/L in the Oslo and Helsinki cohorts, respectively, reflecting differences in disease severity between cohorts. Median sMR was similar in both cohorts, 0.28 (0.22-0.44) and 0.28 mg/L (0.20-0.36), respectively. In both cohorts, sCD163 and sMR levels raised with increasing disease severity (liver enzymes, Mayo score, and enhanced liver fibrosis test). Patients with high baseline levels of sCD163 had shorter transplant-free survival than patients with low baseline levels. Furthermore, sCD163 was associated with transplant-free survival in univariate cox-regression analyses. Both sCD163 and sMR performed better in the Oslo cohort of more severely diseased patients than those in the Helsinki cohort of more mildly diseased patients.
Macrophage activation markers are elevated according to disease severity suggesting an important role of macrophages in PSC. Furthermore, sCD163 was identified as a prognostic marker and predictor of transplant-free survival in PSC (see Visual Abstract, Supplementary Digital Content 4, http://links.lww.com/CTG/A516).
原发性硬化性胆管炎（PSC）是一种进展性肝脏疾病，其特征为胆管炎症和纤维化。巨噬细胞在 PSC 的发展和进展中的作用研究较少。巨噬细胞激活标志物可溶性（s）CD163 和甘露糖受体（sMR）与其他肝脏疾病的严重程度和预后相关，但在 PSC 中尚未进行过研究。我们评估了 sCD163 和 sMR 在 PSC 患者中的疾病严重程度和预后。
我们研究了来自奥斯陆（n = 138）和赫尔辛基（n = 159）的两个独立的 PSC 队列，并分析了血液 sCD163 和 sMR 水平。比较了 Mayo 评分、增强型肝纤维化试验和阿姆斯特丹-牛津模型。
奥斯陆和赫尔辛基队列的 sCD163 中位数（四分位距）分别为 3.32（2.27-5.60）和 1.96（1.47-2.70）mg/L，反映了队列间疾病严重程度的差异。两个队列的 sMR 中位数相似，分别为 0.28（0.22-0.44）和 0.28 mg/L（0.20-0.36）。在两个队列中，sCD163 和 sMR 水平随着疾病严重程度的增加而升高（肝酶、 Mayo 评分和增强型肝纤维化试验）。基线 sCD163 水平较高的患者无移植生存率短于基线 sCD163 水平较低的患者。此外，在单变量 Cox 回归分析中，sCD163 与无移植生存率相关。在疾病更严重的奥斯陆队列中，sCD163 和 sMR 的表现均优于疾病更轻的赫尔辛基队列。
根据疾病严重程度，巨噬细胞激活标志物升高，提示巨噬细胞在 PSC 中具有重要作用。此外，sCD163 被确定为 PSC 的预后标志物和无移植生存率的预测因子（见视觉摘要，补充数字内容 4，http://links.lww.com/CTG/A516）。
