Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China.
Clin Rev Allergy Immunol. 2022 Dec;63(3):342-356. doi: 10.1007/s12016-022-08935-z. Epub 2022 Jun 3.
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.
在自身免疫性肝炎 (AIH) 中，持续的炎症会导致纤维化进展，而传统的生化标志物在预测纤维化进展方面表现相对不理想。在此，我们评估了血清 CD48 (sCD48) 作为 AIH 1 型炎症和纤维化指标的价值。我们首先使用 ELISA 在一个探索性队列中检测 sCD48 水平。在该队列中，与健康对照组 (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) 相比，AIH 患者的 sCD48 水平升高 (12.81ng/mL)，且与组织学炎症和纤维化相关。进一步使用多变量逻辑回归分析，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。基于 sCD48，构建了两个预测评分，用于诊断显著炎症和晚期纤维化 (sCD48-AIH-SI 和 sCD48-AIH-AF)。在此基础上，我们在验证队列中评估和验证了预测能力。在探索性队列中，sCD48 和 sCD48-AIH-SI 对显著炎症的受试者工作特征曲线下面积分别为 0.748 和 0.813。此外，在治疗随访期间，从免疫抑制治疗开始到重新评估活检时，sCD48 水平逐渐下降，与天门冬氨酸转氨酶、总血清 IgG 和纤维化 4 评分下降一致。在重新评估活检队列的 AIH 患者中，sCD48 可预测显著纤维化 (S2-4)。进一步使用免疫组化，AIH 患者的肝 CD48 表达升高，治疗后下降。总之，sCD48 和基于 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 的临床管理。
