Department of Gastroenterology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan.
Department of Evidence-Based Medicine, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan.
Int J Mol Sci. 2022 Aug 29;23(17):9814. doi: 10.3390/ijms23179814.
Primary biliary cholangitis (PBC) has a wide variation in clinical presentation and course. There is no significant correlation between these symptoms and the disease stage, although patients with more advanced stages generally have more symptoms. It is important to develop biomarkers in order to identify patients with an increased risk of complications and end-stage liver disease. This study investigated surrogate markers for risk estimation of PBC-related complications, including a study population of 77 patients with PBC who underwent liver biopsy and were measured for serum levels of macrophage activation markers, soluble CD163 (sCD163), soluble mannose receptor (sMR), and zonulin. Patients with PBC were divided into symptomatic (Group S, n = 20) and asymptomatic (Group A, n = 57) groups. The correlations of histological stages based on both Scheuer and Nakanuma classifications with the three serum markers were investigated. The Nakanuma classification involves grading for liver fibrosis and bile duct loss. The three biomarkers were assessed for their diagnostic ability to identify patients with PBC having high risk of developing complications. The predictive factors of these complications were examined as well. Group S had significantly higher serum sMR (p = 0.011) and sCD163 (p = 0.048) levels versus Group A. A composite index of sMR and sCD163 measurements had significantly better prediction performance than sCD163 alone (p = 0.012), although not when compared to sMR alone (p = 0.129). Serum sMR was an independent factor for developing complications on both univariate (Odds ratio (OR) = 30.20, 95% confidence interval (95% CI): 3.410−267.0, p = 0.00220), and multivariate (OR = 33.70, 95% CI: 3.6600−311.0, p = 0.0019) analyses. Patients with PBC having sMR of ≥56.6 had a higher incidence of clinical complications versus those with a sMR of <56.6. Serum sMR predicts the development of complications in patients with PBC. sMR plus sCD163 showed better predictive power than either marker alone, although the addition of sCD163 did not improve the predictive power of sMR. Future prospective studies are required in order to validate the findings of the present study.
原发性胆汁性胆管炎 (PBC) 的临床表现和病程差异很大。这些症状与疾病阶段之间没有显著相关性，尽管更晚期的患者通常有更多的症状。开发生物标志物对于识别有并发症和终末期肝病风险的患者非常重要。本研究调查了 PBC 相关并发症风险估计的替代标志物，包括 77 名接受肝活检并测量巨噬细胞活化标志物、可溶性 CD163（sCD163）、可溶性甘露糖受体（sMR）和紧密连接蛋白水平的 PBC 患者的研究人群。将 PBC 患者分为有症状（组 S，n = 20）和无症状（组 A，n = 57）组。研究了基于 Scheuer 和 Nakanuma 分类的组织学阶段与三种血清标志物的相关性。Nakanuma 分类涉及肝纤维化和胆管丢失的分级。评估了这三种生物标志物识别有发展并发症高风险的 PBC 患者的诊断能力。还检查了这些并发症的预测因素。与组 A 相比，组 S 的血清 sMR（p = 0.011）和 sCD163（p = 0.048）水平显著更高。sMR 和 sCD163 联合测量的复合指数的预测性能明显优于单独的 sCD163（p = 0.012），尽管与单独的 sMR 相比并不明显（p = 0.129）。在单变量（优势比（OR）= 30.20，95%置信区间（95%CI）：3.410-267.0，p = 0.00220）和多变量（OR = 33.70，95%CI：3.6600-311.0，p = 0.0019）分析中，血清 sMR 是发生并发症的独立因素。与 sMR <56.6 的患者相比，sMR ≥56.6 的 PBC 患者发生临床并发症的发生率更高。血清 sMR 可预测 PBC 患者并发症的发生。sMR 加 sCD163 的预测能力优于单独使用任何一种标志物，尽管添加 sCD163 并未提高 sMR 的预测能力。需要进一步的前瞻性研究来验证本研究的结果。
