在自身免疫性肝炎(AIH)中,持续的炎症有助于纤维化进展,传统的生化标记物表现出相对不令人满意的预测。在这里,我们评估了血清CD48(sCD48)作为1型AIH炎症和纤维化指标的价值.首先使用ELISA在探索性队列中检测sCD48的水平。在这个队列中,与健康对照组相比(4.90ng/mL,P<0.0001),原发性胆汁性胆管炎(7.32ng/mL,P<0.0001),和非酒精性脂肪性肝病(7.76ng/mL,P<0.0001),AIH中sCD48水平升高(12.81ng/mL),并与组织学炎症和纤维化相关。进一步使用多元逻辑回归分析,sCD48被确定为显著炎症(G3-4)和晚期纤维化(S3-4)的独立预测因子。两个预测分数,基于sCD48,被构建用于诊断显著炎症和晚期纤维化(sCD48-AIH-SI和sCD48-AIH-AF,分别)。以这些数据为前提,随后在验证队列中评估并验证了预测能力.在探索性队列中,sCD48和sCD48-AIH-SI的接收器工作特性曲线下的面积,对于严重的炎症,分别为0.748和0.813。此外,在治疗随访期间,从免疫抑制开始到重新评估活检,sCD48水平逐渐降低,与天冬氨酸转氨酶平行,总血清IgG,和纤维化-4评分。对于重新评估活检队列中的AIH患者,sCD48可以预测显著的纤维化(S2-4)。进一步使用免疫组织化学,AIH患者肝CD48表达升高,治疗后降低。总之,基于sCD48和sCD48的预测评分可预测AIH-1的组织学炎症和纤维化。检测sCD48可能有助于AIH的临床治疗。
In autoimmune hepatitis (AIH), the persisting inflammation contributes to fibrosis progression, for which conventional biochemical markers manifest relatively unsatisfactory prediction. Herein, we assessed the value of serum CD48 (sCD48) as an
indicator for inflammation and fibrosis in AIH type 1. The levels of sCD48 were detected first in an exploratory cohort using ELISA. In this cohort, compared with healthy controls (4.90 ng/mL, P < 0.0001), primary biliary cholangitis (7.32 ng/mL, P < 0.0001), and non-alcoholic fatty liver disease (7.76 ng/mL, P < 0.0001), sCD48 levels were elevated in AIH (12.81 ng/mL) and correlated with histological inflammation and fibrosis. Further using multivariate logistic regression analysis, sCD48 was identified as an independent predictor for both significant inflammation (G3-4) and advanced fibrosis (S3-4). Two predictive scores, based on sCD48, were constructed for diagnosing significant inflammation and advanced fibrosis (sCD48-AIH-SI and sCD48-AIH-AF, respectively). Using these data as a premise, predictive abilities were subsequently evaluated and verified in a validation cohort. In the exploratory cohort, the area under the receiver operating characteristic curve of sCD48 and sCD48-AIH-SI, for significant inflammation, were 0.748 and 0.813, respectively. Besides, during treatment follow-up, sCD48 levels gradually decreased from immunosuppression initiation to re-evaluation biopsy, in parallel with aspartate transaminase, total sera IgG, and fibrosis-4 score. For AIH patients in a re-evaluation biopsy cohort, sCD48 could predict significant fibrosis (S2-4). Further using immunohistochemistry, hepatic CD48 expression was elevated in AIH patients and decreased after treatment. In conclusion, sCD48 and sCD48-based predictive scores predict histological inflammation and fibrosis in AIH-1. Detecting sCD48 might help in the clinical management of AIH.