组织金属蛋白酶抑制剂 1 和天冬氨酸转氨酶-血小板比值指数作为非侵入性生物标志物预测儿童肝移植后移植物纤维化。
Tissue inhibitor of metalloproteinase 1 and AST-to-Platelet Ratio Index as noninvasive biomarkers predict allograft fibrosis after pediatric liver transplantation.
机构信息
Pediatric Gastroenterology and Hepatology, University Children´s Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
出版信息
Clin Transplant. 2019 Oct;33(10):e13676. doi: 10.1111/ctr.13676. Epub 2019 Sep 12.
BACKGROUND
Assessing liver fibrosis in patients after liver transplantation is still largely dependent on liver biopsy. Especially in children, noninvasive methods are of utmost importance. We evaluated tissue inhibitor of metalloproteinase 1 (TIMP1) and AST-to-Platelet Ratio Index (APRI) and their potential as serum biomarkers to predict liver allograft fibrosis (LAF) in a pediatric cohort.
METHODS
In this retrospective, observational study, we analyzed 91 protocol liver biopsy specimens from 73 children after pediatric liver transplantation (PLT) and compared histological stage of liver fibrosis using LAF Score (LAFSc) and Ishak Score (IshakSc) to TIMP1-serum concentration and APRI using ROC analysis.
RESULTS
In our cohort, TIMP1 and APRI reliably predict LAF. Depending on the histological scoring system, cutoff values for TIMP1 were 328 ng/mL (IshakSc ≥ IV) and 351 ng/mL (LAFSc ≥ 5) with AUC of 0.86 and 0.98. The cutoff for APRI was 0.8 with AUC of 0.87 (IshakSc ≥ IV) and 0.94 (LAFSc ≥ 5). Using LAFSc, TIMP1 and APRI showed excellent diagnostic accuracy to detect severe LAF (LAFSc ≥ 5) with PPV of ≥ 90% and NPV of 100%.
CONCLUSION
TIMP1 and APRI are accurate biomarkers to predict severe LAF in children. The use of TIMP1 and APRI will not replace but complement liver biopsies after PLT to further improve our understanding of each individual patient.
背景
评估肝移植后患者的肝纤维化仍然在很大程度上依赖于肝活检。特别是在儿童中，非侵入性方法是最重要的。我们评估了组织金属蛋白酶抑制剂 1（TIMP1）和天冬氨酸转氨酶-血小板比值指数（APRI）及其作为血清生物标志物预测小儿肝移植后肝纤维化（LAF）的潜力。
方法
在这项回顾性观察研究中，我们分析了 73 例小儿肝移植后 91 例协议肝活检标本，并使用 LAF 评分（LAFSc）和 Ishak 评分（IshakSc）比较肝纤维化的组织学分期，用 ROC 分析比较 TIMP1 血清浓度和 APRI。
结果
在我们的队列中，TIMP1 和 APRI 可靠地预测 LAF。根据组织学评分系统，TIMP1 的截断值为 328ng/mL（IshakSc≥IV）和 351ng/mL（LAFSc≥5），AUC 为 0.86 和 0.98。APRI 的截断值为 0.8，AUC 为 0.87（IshakSc≥IV）和 0.94（LAFSc≥5）。使用 LAFSc，TIMP1 和 APRI 显示出良好的诊断准确性，以检测严重的 LAF（LAFSc≥5），PPV≥90%，NPV 为 100%。
结论
TIMP1 和 APRI 是预测儿童严重 LAF 的准确生物标志物。TIMP1 和 APRI 的使用不会替代但会补充 PLT 后的肝活检，以进一步提高我们对每个患者的了解。
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