Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
Biomarkers and Research, Nordic Bioscience, Herlev, Denmark.
Sci Rep. 2023 Apr 13;13(1):6103. doi: 10.1038/s41598-023-33100-7.
Detecting patients with early post-transplant fibrosis after liver transplantation (LT) is very important. Non-invasive tests are needed to avoid liver biopsies. We aimed to detect fibrosis in liver transplant recipients (LTR) using extracellular matrix (ECM) remodeling biomarkers. ECM biomarkers for type III (PRO-C3), IV (PRO-C4), VI (PRO-C6) and XVIII (PRO-C18L) collagen formation and type IV collagen degradation (C4M) were measured by ELISA in prospectively collected, cryopreserved plasma samples (n = 100) of LTR with paired liver biopsies from a protocol biopsy program. Fibrosis ≥ F2 was present in 29% of patients (median 44 months post-LT). APRI and FIB-4 neither identified significant fibrosis nor were correlated with histopathological fibrosis scores, while ECM biomarkers (AUCs 0.67-0.74) did. The median levels of PRO-C3 (15.7 vs. 11.6 ng/ml; p = 0.002) and C4M (22.9 vs. 11.6 ng/ml; p = 0.006) levels were elevated in T-cell-mediated rejection compared to normal graft function. The median levels of PRO-C4 (178.9 vs. 151.8 ng/ml; p = 0.009) and C4M (18.9 vs. 16.8 ng/ml; p = 0.004) levels were increased if donor-specific antibodies were present. PRO-C6 had the highest sensitivity (100%), NPV (100%) and negative likelihood-ratio (0) for graft fibrosis. To conclude, ECM biomarkers are helpful in identifying patients at risk of relevant graft fibrosis.
检测肝移植（LT）后早期纤维化的患者非常重要。需要进行非侵入性检查以避免肝活检。我们旨在使用细胞外基质（ECM）重塑生物标志物检测肝移植受者（LTR）的纤维化。通过 ELISA 测量 ECM 标志物 III 型（PRO-C3）、IV 型（PRO-C4）、VI 型（PRO-C6）和 XVIII 型（PRO-C18L）胶原形成和 IV 型胶原降解（C4M），前瞻性收集了来自方案活检计划的 LTR 的冷冻保存血浆样本（n=100），并进行配对肝活检。29%的患者存在纤维化≥F2（LT 后中位数 44 个月）。APRI 和 FIB-4 既不能识别显著纤维化，也与组织病理学纤维化评分无关，而 ECM 生物标志物（AUCs 0.67-0.74）则可以。与正常移植物功能相比，T 细胞介导的排斥反应中 PRO-C3（15.7 与 11.6ng/ml；p=0.002）和 C4M（22.9 与 11.6ng/ml；p=0.006）的中位水平升高。与供体特异性抗体存在时相比，PRO-C4（178.9 与 151.8ng/ml；p=0.009）和 C4M（18.9 与 16.8ng/ml；p=0.004）的中位水平升高。如果存在供体特异性抗体，PRO-C6 的敏感性（100%）、NPV（100%）和负似然比（0）最高。总之，ECM 生物标志物有助于识别有相关移植物纤维化风险的患者。
