Leucine-Rich Alpha-2-Glycoprotein as a non-invasive biomarker for pediatric acute appendicitis: a systematic review and meta-analysis

Eur J Pediatr. 2023 Jul;182(7):3033-3044. doi: 10.1007/s00431-023-04978-2. Epub 2023 May 6.

Abstract

The aim of this study was to analyze the diagnostic performance of Leucine-Rich Alpha-2-Glycoprotein (LRG1) in pediatric acute appendicitis (PAA). We conducted a systematic review of the literature in the main databases of medical bibliography. Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using the QUADAS2 index. A synthesis of the results, standardization of the metrics and 4 random-effect meta-analyses were performed. Eight studies with data from 712 participants (305 patients with confirmed diagnosis of PAA and 407 controls) were included in this review. The random-effect meta-analysis of serum LRG1 (PAA vs control) resulted in a significant mean difference (95% CI) of 46.76 μg/mL (29.26-64.26). The random-effect meta-analysis for unadjusted urinary LRG1 (PAA vs control) resulted in a significant mean difference (95% CI) of 0.61 μg/mL (0.30-0.93). The random-effect meta-analysis (PAA vs control) for urinary LRG1 adjusted for urinary creatinine resulted in a significant mean difference (95% CI) of 0.89 g/mol (0.11-1.66). Conlusion: Urinary LRG1 emerges as a potential non-invasive biomarker for the diagnosis of PAA. On the other hand, due to the high between-study heterogeneity, the results on serum LRG1 should be interpreted with caution. The only study that analyzed salivary LRG1 showed promising results. Further prospective studies are needed to confirm these findings. What is Known: • Pediatric acute appendicitis continues to be a pathology with a high rate of diagnostic error. • Invasive tests, although useful, are a source of stress for patients and their parents. What is New: • LRG1 emerges as a promising urinary and salivary biomarker for the noninvasive diagnosis of pediatric acute appendicitis.

Keywords: Acute appendicitis; Children; LRG1; Leucine-Rich Alpha-2-Glycoprotein; Meta-analysis; Pediatric; Sensitivity; Specificity; Systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Acute Disease
  • Appendicitis* / diagnosis
  • Biomarkers / blood
  • Child
  • Glycoproteins* / blood
  • Humans

Substances

  • Biomarkers
  • Glycoproteins
  • LRG1 protein, human