Bossen Lars, Rebora Paola, Bernuzzi Francesca, Jepsen Peter, Gerussi Alessio, Andreone Pietro, Galli Andrea, Terziroli Benedetta, Alvaro Domenico, Labbadia Giancarlo, Aloise Chiara, Baiocchi Leonardo, Giannini Edoardo, Abenavoli Ludovico, Toniutto Pierluigi, Marra Fabio, Marzioni Marco, Niro Grazia, Floreani Annarosa, Møller Holger J, Valsecchi Maria G, Carbone Marco, Grønbaek Henning, Invernizzi Pietro
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan Bicocca, Milan, Italy.
Liver Int. 2020 Jun;40(6):1408-1414. doi: 10.1111/liv.14466. Epub 2020 Apr 24.
In primary biliary cholangitis (PBC), macrophages are involved in liver inflammation and fibrosis. The macrophage activation markers, soluble (s)CD163 and mannose receptor (sMR) are associated with liver disease severity and prognosis in other chronic liver diseases. We aimed to investigate sCD163 and sMR in patients with PBC.
We investigated PBC patients from the Italian PBC Study Group cohort and measured macrophage activation markers in serum at study enrolment. Patients were followed from enrolment until they experienced an event or were censored at their last visit. Events were defined as follows: (a) death from a liver-related cause; or (b) liver transplantation (LT) for PBC. We used Cox regression to investigate the association between sCD163 and sMR and long-term prognosis.
In total, 202 PBC patients were included. Median age was 62 years (interquartile range (IQR), 53-71) at enrolment and 93% were women. Median sCD163 was 3.43 mg/L (IQR 2.48-5.35) and median sMR was 0.35 mg/L (IQR 0.28-0.45). There was an increase in sCD163 and sMR with increasing alkaline phosphatase. Two hundred and one patients were followed for a median of 8.6 years, and sCD163 and sMR predicted long-term risk of liver-related death or LT in univariate analyses, while sCD163 was also associated with outcome after confounder adjusting (adjusted HR = 1.14, 95% CI 1.00-1.30). Finally, we showed an increase in the prediction accuracy of poor outcome by adding sCD163 to the UK-PBC risk score.
The macrophage activation markers sCD163 and sMR represent a non-invasive measure of PBC disease severity that provides useful long-term prognostic information.
在原发性胆汁性胆管炎（PBC）中，巨噬细胞参与肝脏炎症和纤维化过程。巨噬细胞活化标志物，可溶性（s）CD163和甘露糖受体（sMR）与其他慢性肝病的疾病严重程度和预后相关。我们旨在研究PBC患者中的sCD163和sMR。
我们调查了意大利PBC研究组队列中的PBC患者，并在研究入组时测量了血清中的巨噬细胞活化标志物。患者从入组开始随访，直至发生事件或在最后一次就诊时被 censored。事件定义如下：（a）因肝脏相关原因死亡；或（b）因PBC进行肝移植（LT）。我们使用Cox回归研究sCD163和sMR与长期预后之间的关联。
总共纳入了202例PBC患者。入组时的中位年龄为62岁（四分位间距（IQR），53 - 71岁），93%为女性。sCD163的中位数为3.43mg/L（IQR 2.48 - 5.35），sMR的中位数为0.35mg/L（IQR 0.28 - 0.45）。随着碱性磷酸酶升高，sCD163和sMR也升高。201例患者的中位随访时间为8.6年，在单变量分析中，sCD163和sMR预测了肝脏相关死亡或LT的长期风险，而在调整混杂因素后，sCD163也与结局相关（调整后的HR = 1.14，95%CI 1.00 - 1.30）。最后，我们发现将sCD163添加到英国PBC风险评分中可提高对不良结局的预测准确性。
巨噬细胞活化标志物sCD163和sMR代表了一种PBC疾病严重程度的非侵入性测量方法，可提供有用的长期预后信息。
