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生长分化因子-15作为镰状细胞病肝纤维化的非侵入性生物标志物。

Growth differentiation factor-15 as a non-invasive biomarker of liver fibrosis in sickle cell disease.

作者信息

Manganas Konstantinos, Delicou Sophia, Hadziyannis Emilia, Giannouli Stavroula, Koskinas John

机构信息

Thalassemia and Sickle Cell Unit, Hippokration General Hospital, 114 Vas. Sofias, 11527, Athens, Greece.

Second Department of Internal Medicine and Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece.

出版信息

Int J Hematol. 2025 Jul 13. doi: 10.1007/s12185-025-04035-8.

Abstract

This study aimed to evaluate the relationship between growth differentiation factor-15 (GDF-15) levels and liver fibrosis in patients with sickle cell disease (SCD) and assess the diagnostic performance of GDF-15 as a non-invasive biomarker. Thirty patients with SCD were categorized into two groups based on fibrosis severity (≥ F2 vs. < F2) determined by Fibroscan, AST to Platelet Ratio Index (APRI) and FIB-4. GDF-15 levels were compared between groups, and independent predictors of GDF-15 were identified by multiple linear regression. Patients with significant liver fibrosis (≥ F2) had significantly higher GDF-15 levels. Multivariate linear regression revealed that GDF-15 concentration was independently associated with liver elastography values (β = 0.619, p = 0.002). The area under the curve for detecting significant fibrosis using GDF-15 as a diagnostic test was 0.835 (95% CI: 0.686-0.983, p = 0.002). A GDF-15 cut-off of 4200 pg/ml had a positive predictive value of 73.6%, a negative predictive value of 81.8%, sensitivity of 87.5% and specificity of 64.3%. In conclusion, GDF-15 is strongly associated with liver fibrosis in SCD and demonstrates high diagnostic accuracy as a non-invasive biomarker. Given its role in inflammation, oxidative stress, and iron metabolism, GDF-15 may serve as a valuable tool for early fibrosis detection and disease monitoring.

摘要

本研究旨在评估镰状细胞病(SCD)患者中生长分化因子-15(GDF-15)水平与肝纤维化之间的关系,并评估GDF-15作为一种非侵入性生物标志物的诊断性能。根据Fibroscan、AST与血小板比值指数(APRI)和FIB-4确定的纤维化严重程度(≥F2 vs.<F2),将30例SCD患者分为两组。比较两组之间的GDF-15水平,并通过多元线性回归确定GDF-15的独立预测因素。有显著肝纤维化(≥F2)的患者GDF-15水平显著更高。多元线性回归显示,GDF-15浓度与肝脏弹性成像值独立相关(β = 0.619,p = 0.002)。以GDF-15作为诊断测试检测显著纤维化的曲线下面积为0.835(95%CI:0.686 - 0.983,p = 0.002)。GDF-15临界值为4200 pg/ml时,阳性预测值为73.6%,阴性预测值为81.8%,敏感性为87.5%,特异性为64.3%。总之,GDF-15与SCD中的肝纤维化密切相关,并作为一种非侵入性生物标志物显示出高诊断准确性。鉴于其在炎症、氧化应激和铁代谢中的作用,GDF-15可能是早期纤维化检测和疾病监测的有价值工具。

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