# Evaluation of Five Plasma miRNAs as Biomarkers for Minimally Invasive Staging of Liver Fibrosis in β-Thalassaemia Patients

## TL;DR

This study tested five plasma miRNAs as potential biomarkers for liver fibrosis in β-thalassaemia patients but found limited effectiveness for precise staging.

## Contribution

The study evaluates the performance of specific miRNAs for fibrosis staging in β-thalassaemia, highlighting limitations due to blood miRNA changes in haemoglobinopathies.

## Key findings

- Candidate miRNAs showed fair discriminatory performance with area-under-the-curve values between 0.7 and 0.917.
- No statistically significant variation in miRNA expression was observed across fibrosis stages.
- The study suggests that blood miRNA transcriptome changes in haemoglobinopathies may reduce miRNA effectiveness for fibrosis staging.

## Abstract

Iron overload-driven liver fibrosis is a major concern in β-thalassaemia patients, but non-invasive or minimally invasive biomarkers for fibrosis staging remain limited. This study evaluated five plasma microRNAs (let-7a, miR-21, miR-29a, miR-34a, and miR-122) as potential markers for distinguishing liver fibrosis stages in β-thalassaemia. Plasma samples from 40 patients with fibrosis stages F0–F1 to F4 were analysed using RT-qPCR, normalised against the arithmetic mean of reference miRNAs miR-16 and miR-221. Expression levels of candidate miRNAs showed no statistically significant variation across stages, and logistic regression and ROC analyses revealed fair discriminatory performance for individual miRNAs and their combinations in selected stage comparisons. Notably, while for the discrimination of different fibrosis stages all five candidate miRNAs tested showed fair area-under-the-curve values between 0.7 and 0.8 individually and up to 0.917 in combination, none of these findings reached statistical significance. These results suggest that while the selected set of miRNAs reflects liver injury, its performance for precise fibrosis staging in β-thalassaemia is limited. A key cause for the low discriminatory power of these miRNAs may be the overall change of the blood miRNA transcriptome in haemoglobinopathies. The results indicate the need for validation in larger cohorts based on larger miRNA panels or the use of alternative source materials to improve diagnostic performance.