血浆FSTL-1作为晚期肝纤维化患者的一种非侵入性诊断生物标志物。
Plasma FSTL-1 as a noninvasive diagnostic biomarker for patients with advanced liver fibrosis.
作者信息
Li Wenzhu, Chi Yongquan, Xiao Xuan, Li Junda, Sun Mingmin, Sun Shanke, Xu Wei, Zhang Long, Li Xiaoguo, Cheng Feng, Qi Xiaolong, Rao Jianhua
机构信息
Hepatobiliary Center, The First Affiliated Hospital with Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.
Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
出版信息
Hepatology. 2024 Nov 21. doi: 10.1097/HEP.0000000000001167.
BACKGROUND AND AIMS
Reliable novel noninvasive biomarkers for the diagnosis of advanced liver fibrosis are urgently needed in clinical practice. We aimed to investigate the accuracy of plasma Follistatin-like protein 1 (FSTL-1) in the diagnosis of advanced liver fibrosis in chronic liver diseases.
APPROACH AND RESULTS
We collected cross-sectional clinical data for a derivation cohort (n = 86) and a validation cohort (n = 431), totaling 517 subjects with liver biopsy. Advanced liver fibrosis was defined by the METAVIR pathological score (F ≥3). Dual cutoff values for diagnosis were explored. In the derivation cohort, plasma FSTL-1 levels were significantly elevated in patients with advanced liver fibrosis, with an AUROC of 0.85 (95% CI, 0.75-0.96). In the validation cohort, plasma FSTL-1 maintained good diagnostic performance, with an AUROC of 0.88 (95% CI, 0.83-0.92). Plasma FSTL-1 levels were significantly associated with individual histological features of the METAVIR scoring system, including interface hepatitis, lobular necrosis, and hepatocellular ballooning (p < 0.0001). A cutoff value ≤ 0.43 ng/mL was the optimal rule-out threshold, with a sensitivity of 84.62% (95% CI, 76.46%-90.30%) and a specificity of 79.51% (95% CI, 74.81%-83.53%), while ≥0.50 ng/mL was the best rule-in threshold, with a specificity of 86.41% (95% CI, 81.06%-90.43%) and a sensitivity of 70.67% (95% CI, 64.41%-76.23%).
CONCLUSIONS
Plasma FSTL-1 has high diagnostic accuracy and could potentially reduce the need for liver biopsy in identifying patients with advanced liver fibrosis.
背景与目的
临床实践中迫切需要可靠的新型非侵入性生物标志物来诊断晚期肝纤维化。我们旨在研究血浆卵泡抑素样蛋白1（FSTL-1）在诊断慢性肝病晚期肝纤维化中的准确性。
方法与结果
我们收集了一个推导队列（n = 86）和一个验证队列（n = 431）的横断面临床数据，共有517例进行了肝活检的受试者。晚期肝纤维化由METAVIR病理评分（F≥3）定义。探索了诊断的双重临界值。在推导队列中，晚期肝纤维化患者的血浆FSTL-1水平显著升高，曲线下面积（AUROC）为0.85（95%置信区间，0.75 - 0.96）。在验证队列中，血浆FSTL-1保持了良好的诊断性能，AUROC为0.88（95%置信区间，0.83 - 0.92）。血浆FSTL-1水平与METAVIR评分系统的个体组织学特征显著相关，包括界面性肝炎、小叶坏死和肝细胞气球样变（p < 0.0001）。≤0.43 ng/mL的临界值是最佳排除阈值，敏感性为84.62%（95%置信区间，76.46% - 90.30%），特异性为79.51%（95%置信区间，74.81% - 83.53%），而≥0.50 ng/mL是最佳纳入阈值，特异性为86.41%（95%置信区间，81.06% - 90.43%），敏感性为70.67%（95%置信区间，64.41% - 76.23%）。
结论
血浆FSTL-1具有较高的诊断准确性，在识别晚期肝纤维化患者时可能减少肝活检的需求。
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