Tissue inhibitor of metalloproteinase 1 and AST-to-Platelet Ratio Index as noninvasive biomarkers predict allograft fibrosis after pediatric liver transplantation.

Abstract

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. 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. In our cohort, TIMP1 and APRI reliably predict LAF. Depending on the histological scoring system, cutoff values for TIMP1 were 328ng/mL (IshakSc≥IV) and 351ng/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%. 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.