Impact of steroid therapy on pediatric acute liver failure: prognostic implication and interplay between TNF-α and miR-122

Abstract

BACKGROUND: Acute liver failure (ALF) is a rare illness marked by rapid deterioration of liver function, leading to high morbidity and mortality rates, particularly in children. While steroids have been observed to correlate with improved survival, evidence supporting their efficacy in ALF children remains limited. miR-122, a liver-specific microRNA, plays a pivotal role in liver pathology, with its expression significantly altered in various liver diseases. Thus, it is considered a potential biomarker for disease progression, aids in prognosis, and identifies therapeutic targets. Our study aims to assess the expression of miR-122 in 24 children with ALF, both before and after steroid therapy, alongside its relationship with tumor necrosis factor-α (TNF-α), to better understand its potential role in treatment response and disease outcomes. miR-122 levels were determined using quantitative real-time RT-PCR (qRT-PCR), while TNF-α levels were assessed using enzyme-linked immunosorbent assay (ELISA) in patient sera. RESULTS: In ALF children who survived after steroid treatment, miR-122 was markedly decreased compared to both pre-treatment levels (p = 0.003) and levels in deceased patients (p = 0.01). In addition, TNF-α levels significantly increased in surviving patients compared to pre-treatment levels (p = 0.008) and levels in deceased children (p = 0.028). A negative correlation was observed between TNF-α and miR-122 following steroids (r=-0.46, p = 0.04). miR-122 demonstrated 72% sensitivity and 67% specificity in distinguishing survivors and non-survivors, as indicated by its receiver-operated characteristic curve. A positive correlation was found between miR-122 before steroid therapy and both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) before (r = 0.641, p = 0.002 and r = 0.512, p = 0.02, respectively) and after (r = 0.492, p = 0.03 and r = 0.652, p = 0.003, respectively) steroids treatment. CONCLUSION: Our data implies that lower miR-122 levels in steroids-treated ALF children are associated with a better outcome. Although miR-122 is not a strong standalone marker, it could be valuable in a biomarker panel. The increased TNF-α levels and decreased miR-122 expression indicate their involvement in the disease's pathophysiology. More studies are needed to validate our results.