Tamirna

Adult hypophosphatasia (HPP) patients present with diffuse heterogenous symptoms often mimicking rheumatological diseases or osteoporosis and therefore accompanied by delayed diagnosis. The aim of this study was to identify circulating microRNAs (miRNAs) in adult HPP patients and to identify potential associations with clinical patients' characteristics.

We utilized untargeted miRNA biomarker discovery by small RNA-sequencing to investigate cell-free miRNA profiles in 24 adult HPP patients (pathogenic variant of the ALPL gene, HPP-related clinical symptoms, and repeatedly low alkaline phosphatase) and 24 healthy controls (CTRL).

Patients and CTRL were comparable in age (47.9 ± 14.2 vs 45.9 ± 8.8 years, P = .980) and sex (55.5% vs 47.8% females, P = 1.000). In total, 91% of patients reported musculoskeletal pain, 41% diffuse neurological symptoms, and 64% history of fractures. In total, 84 miRNAs were significantly differently expressed between HPP and CTRL in next-generation sequencing analysis (P < .05). Of these, 14 miRNAs were selected (selection criteria: P < .05, tissue specificity index >0.7, log2 fold change >+0.8 or <−0.8) for validation using RT-qualitative PCR, which verified 6 of 14 selected miRNAs (P < .05; miR-122-3p, miR-140-5p, miR-143-3p, miR-155-5p, miR-451a, miR-92a-3p). Target prediction and enrichment analysis identified associations with the musculoskeletal system and the central nervous system. In total, 37 miRNAs correlated with alkaline phosphatase levels, but only 3 miRNAs with pyridoxal-5′-phosphate.

These findings highlight a profound involvement of multiple organ systems and the potential of miRNAs as biomarkers for the effect of HPP on various systems.

NCT04018287

Posthepatectomy liver failure (PHLF) continues to be the most significant factor-determining outcome after hepatic resection, accounting for nearly half of postoperative mortality. In this study, we evaluated whether a newly developed commercially available test measuring circulating microRNAs (miRs) could predict PHLF and compared it with other established liver function tests.

A total of 329 patients undergoing liver resection were included and postoperative outcome was assessed. Our previously described P-score, calculated on the basis of three circulating microRNAs (miR-122-5p, miR-192-5p, miR-151a-5p) using the hepatomiR® CE-IVD test, was evaluated and compared with other predictors of PHLF, namely indocyanine green (ICG)-clearance as well as the combined aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and albumin–bilirubin grade (ALBI) score.

Compared with both other liver function tests, P-scores were superior in predicting PHLF and PHLF grades B and C (PHLF B + C) (PHLF B + C: hepatomiR® AUC = 0.835, APRI + ALBI AUC = 0.807; retention rate at 15 min (R15) AUC = 0.690; plasma disappearance rate (PDR) AUC = 0.691). We also documented a superior positive (77%) and negative predictive value (> 90%) for PHLF, along with a close association with postoperative overall survival. A health-economic analysis demonstrated the cost-effectiveness of hepatomiR® in terms of life-years gained due to improved patient risk stratification.

The hepatomiR® P-score outperforms established liver function tests utilized in daily clinical practice for predicting PHLF and identifies patients possibly better served with alternative treatments. A health-economic assessment allowed us to demonstrate that optimized preoperative risk-assessment leads to a cost-effective improvement in patient outcomes.