Incremental diagnostic value of HSP-70, presepsin, and HO-1 for differentiating acute appendicitis from nonsurgical abdominal pain in children: a prospective cohort study

BACKGROUND: Diagnosing acute appendicitis in children remains challenging when clinical findings, laboratory results, or imaging are equivocal. We evaluated the individual and incremental diagnostic performance of serum HSP-70, presepsin, and heme oxygenase-1 (HO-1) for differentiating histopathologically confirmed appendicitis from nonsurgical abdominal pain. METHODS: This prospective single-centre cohort included 68 consecutive children aged 3-17 years with suspected acute appendicitis. Final classification identified 34 children with histopathologically confirmed appendicitis and 34 with nonsurgical abdominal pain. Biomarker measurements were available for 63 children (34 appendicitis; 29 nonsurgical abdominal pain). Individual discrimination was assessed by receiver operating characteristic analysis. Exploratory logistic regression assessed whether each biomarker improved discrimination beyond a model comprising white blood cell count, neutrophil percentage, and C-reactive protein. RESULTS: HSP-70 was nominally higher in appendicitis than nonsurgical abdominal pain (median, 26.30 vs. 25.70 ng/mL; unadjusted P = 0.044), but this difference was not significant after Holm adjustment (P = 0.132). Presepsin was numerically higher (unadjusted P = 0.117), and HO-1 concentrations were similar (P = 0.557). HSP-70 had the highest individual AUC (0.649; 95% CI, 0.510-0.788), followed by presepsin (0.616; 95% CI, 0.473-0.758) and HO-1 (0.544; 95% CI, 0.396-0.691). The conventional laboratory-marker model had an apparent AUC of 0.749 (95% CI, 0.627-0.872). Addition of HSP-70, presepsin, and HO-1 yielded apparent AUCs of 0.779, 0.764, and 0.745, respectively; none significantly improved discrimination. CONCLUSIONS: HSP-70 and presepsin may reflect inflammatory or tissue-stress activity, but none of the biomarkers demonstrated statistically robust incremental diagnostic value beyond routine laboratory markers. Their role in suspected paediatric appendicitis remains uncertain and should be assessed alongside clinical evaluation and appropriate imaging.