Tumor Necrosis Factor Alpha as a Predictive Biomarker for Hirschsprung-Associated Enterocolitis: A Case-Control Study

Background: The most dangerous consequence of Hirschsprung's disease (HD) is Hirschsprung-associated enterocolitis (HAEC), which can have a 30% fatality rate. Due to a lack of trustworthy biomarkers, early diagnosis and prediction are still difficult. The expression of tumor necrosis factor alpha (TNF-α) was examined in this study as a potential biomarker for the development of HAEC.Methods: From January 2024 to June 2025, a case-control study was carried out at the Dr. Saiful Anwar Hospital in Malang, Indonesia. Twelve children were recruited, five of whom had HAEC and seven of whom had HD without. Both ganglionic and aganglionic intestinal segments were subjected to histopathological investigation utilizing hematoxylin and eosin staining and immunohistochemistry evaluation of TNF-α expression. The number of positive cells per high-power field was used to quantify TNF-α expression.Results: In the aganglionic segments of HAEC patients, TNF-α expression was substantially higher than that of HD patients (50.80 ± 8.47 vs. 25.14 ± 6.23 positive cells/field; p = 0.0127). Ganglionic segments did not significantly differ across groups (28.20 ± 5.67 vs. 21.43 ± 5.24; p = 0.0778). More severe histological grades, including neutrophil infiltration, mucosal ulceration, and widespread crypt abscesses, were seen in HAEC patients.Conclusions: The expression of TNF-α in aganglionic segments is a trustworthy biomarker for the development of HAEC. In order to improve patient outcomes, elevated TNF-α levels may aid in early diagnosis and direct focused therapy measures.