Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
J Gastroenterol Hepatol. 2018 Feb;33(2):484-491. doi: 10.1111/jgh.13849.
Liver macrophages are activated in chronic hepatitis B virus (CHB) infection and play a pivotal role in hepatic inflammation and fibrosis. However, their role during antiviral treatment is unclear. The soluble (s) macrophage activation markers, sCD163 and mannose receptor (sMR), are released during liver damage, and their serum levels reflect liver disease severity and portal hypertension. We aimed to investigate associations between sCD163 and sMR and histopathological activity and fibrosis and changes in sCD163, sMR, and hepatic CD163-expression following antiviral treatment in CHB patients.
We assessed Ishak histological necroinflammatory activity and fibrosis scores in liver biopsies from 254 CHB patients and serially in 71 patients before and after nucleoside-analogue treatment. Liver CD163-expression was semi-quantitatively determined by immunohistochemistry and serum sCD163 and sMR measured by enzyme-linked immunosorbent assays.
Before treatment, the mean levels of sCD163 and sMR were 3.57 (SD 1.72) mg/L and 0.35 (0.12) mg/L. sCD163 and sMR increased with histological inflammatory activity (sCD163: r = 0.46, P < 0.00001; sMR: r = 0.48, P < 0.00001) and correlated positively with fibrosis (sCD163: OR 1.16, 95% CI:1.03-1.31; sMR: OR 1.34, 95% CI:1.13-1.59); both were markers of fibrosis independent of other biochemical parameters and risk factors. Antiviral treatment significantly reduced sCD163 (3.76 [1.46] vs 2.31 [0.95], P < 0.00001), sMR (0.37 [0.1] vs 0.29 [0.07], P < 0.00001) and hepatic CD163-expression (P = 0.0002).
The macrophage activation markers sCD163 and sMR were associated with activity and fibrosis in liver biopsies from CHB patients. Both serum markers decreased with antiviral treatment, along with decreased hepatic CD163 expression.
肝巨噬细胞在慢性乙型肝炎病毒（CHB）感染中被激活，在肝炎症和纤维化中发挥关键作用。然而，其在抗病毒治疗中的作用尚不清楚。可溶性（s）巨噬细胞激活标志物 sCD163 和甘露糖受体（sMR）在肝损伤时释放，其血清水平反映肝脏疾病的严重程度和门脉高压。我们旨在研究 CHB 患者抗病毒治疗前后 sCD163 和 sMR 与组织病理学活动和纤维化的关系，以及 sCD163、sMR 和肝 CD163 表达的变化。
我们评估了 254 例 CHB 患者肝活检的 Ishak 组织学坏死性炎症活动和纤维化评分，并在 71 例患者抗病毒治疗前后进行了连续评估。通过免疫组织化学半定量测定肝 CD163 表达，通过酶联免疫吸附试验测定血清 sCD163 和 sMR。
治疗前，sCD163 和 sMR 的平均水平分别为 3.57（SD 1.72）mg/L 和 0.35（0.12）mg/L。sCD163 和 sMR 随着组织学炎症活动的增加而增加（sCD163：r=0.46，P<0.00001；sMR：r=0.48，P<0.00001），与纤维化呈正相关（sCD163：OR 1.16，95%CI：1.03-1.31；sMR：OR 1.34，95%CI：1.13-1.59）；这两个标志物都是独立于其他生化参数和危险因素的纤维化标志物。抗病毒治疗显著降低了 sCD163（3.76[1.46] vs 2.31[0.95]，P<0.00001）、sMR（0.37[0.1] vs 0.29[0.07]，P<0.00001）和肝 CD163 表达（P=0.0002）。
巨噬细胞激活标志物 sCD163 和 sMR 与 CHB 患者肝活检的活动和纤维化有关。两种血清标志物均随抗病毒治疗而降低，肝 CD163 表达也随之降低。
