Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Hepatol Commun. 2023 Mar 24;7(4). doi: 10.1097/HC9.0000000000000068. eCollection 2023 Apr 1.
The macrophage activation marker soluble (s)CD163 is associated with disease severity and prognosis in patients with primary biliary cholangitis (PBC). Ursodeoxycholic acid (UDCA) treatment attenuates fibrosis progression in PBC patients, but its effect on macrophage activation is unclear. We examined the effect of UDCA on macrophage activation, as determined by sCD163 levels.
We included 2 cohorts of PBC patients; 1 cohort with prevalent PBC patients, and 1 cohort of incident PBC patients before start of UDCA treatment and with follow-up after 4 weeks and 6 months. We measured sCD163 and liver stiffness in both cohorts. Further, we measured sCD163 and TNF-α shedding in vitro in monocyte-derived macrophages after UDCA and lipopolysaccharide incubation.
We included 100 patients with prevalent PBC [93% women, median age 63 y (interquartile range: 51-70)] and 47 patients with incident PBC [77% women, median age 60 y (49-67)]. Prevalent PBC patients had a lower median sCD163 of 3.54 mg/L (2.77-4.72) than incident PBC patients with a median sCD163 of 4.33 mg/L (2.83-5.99) at inclusion. Patients with an incomplete response to UDCA and patients with cirrhosis had higher sCD163 than responders to UDCA and noncirrhosis patients. After 4 weeks and 6 months of UDCA treatment median sCD163 decreased by 4.6% and 9.0%, respectively. In in vitro experiments, UDCA attenuated shedding of TNF-α, but not sCD163, from monocyte-derived macrophages.
In PBC patients, sCD163 levels correlated with liver disease severity and treatment response to UDCA. Further, after 6 months of UDCA treatment, we observed a decrease in sCD163, which may be related to the treatment.
巨噬细胞活化标志物可溶性（s）CD163 与原发性胆汁性胆管炎（PBC）患者的疾病严重程度和预后相关。熊去氧胆酸（UDCA）治疗可减轻 PBC 患者的纤维化进展，但对巨噬细胞活化的影响尚不清楚。我们研究了 UDCA 对 sCD163 水平确定的巨噬细胞活化的影响。
我们纳入了两批 PBC 患者；一批是现患 PBC 患者，另一批是在开始 UDCA 治疗前和治疗后 4 周和 6 个月随访的新发 PBC 患者。我们在这两批患者中测量了 sCD163 和肝硬度。此外，我们在 UDCA 和脂多糖孵育后测量了单核细胞衍生的巨噬细胞中 sCD163 和 TNF-α的脱落。
我们纳入了 100 例现患 PBC 患者[93%为女性，中位年龄 63 岁（四分位间距：51-70）]和 47 例新发 PBC 患者[77%为女性，中位年龄 60 岁（49-67）]。现患 PBC 患者的 sCD163 中位数为 3.54mg/L（2.77-4.72），低于纳入时 sCD163 中位数为 4.33mg/L（2.83-5.99）的新发 PBC 患者。对 UDCA 反应不完全的患者和肝硬化患者的 sCD163 高于对 UDCA 有反应的患者和非肝硬化患者。UDCA 治疗 4 周和 6 个月后，sCD163 中位数分别下降了 4.6%和 9.0%。在体外实验中，UDCA 减弱了单核细胞衍生的巨噬细胞中 TNF-α的脱落，但不能减弱 sCD163 的脱落。
在 PBC 患者中，sCD163 水平与肝脏疾病严重程度和 UDCA 治疗反应相关。此外，在 UDCA 治疗 6 个月后，我们观察到 sCD163 下降，这可能与治疗有关。
