Altered T cell immune profile and its prognostic implications in children with portal hypertension: A pilot study

Abstract Objectives Immune dysregulation in paediatric portal hypertension (PHT) is poorly understood. We aimed to characterise T cell phenotype and function and circulating immune mediators in children with PHT according to disease aetiology. Methods Forty‐four children with PHT (27 chronic liver disease [CLD]‐related and 17 portal vein thrombosis [PVT]‐related) and 15 healthy controls were prospectively enrolled. Peripheral and portal blood samples were analysed using multiparameter flow cytometry and ELISA to assess T cell subsets, chemokine receptors, cytokines and soluble immune markers. Analyses examined group differences and correlations with liver stiffness and bleeding history. Results PHT was associated with reduced circulating T cells, altered immune phenotypes and impaired effector function. CLD‐related PHT exhibited a pronounced pro‐inflammatory profile, with elevated IFN‐γ, TNF‐α, MMP7 and soluble PD‐L1 and increased CD39 and PD‐1. PVT‐related PHT showed relatively preserved liver function and milder systemic inflammation but altered T cell trafficking, characterised by increased CCR4 and reduced CXCR3 expression. Elevated CXCL9 correlated with CXCR3 expression. T cells in the portal circulation displayed reduced cytokine production and cytotoxicity, suggesting functional adaptation within the hepatic microenvironment. Liver stiffness correlated positively with pro‐inflammatory cytokines and immune‐regulatory markers. Conclusions Paediatric PHT is characterised by aetiology‐specific T cell dysregulation. CLD‐related PHT predominantly features chronic inflammation and T cell exhaustion, whereas PVT‐related PHT shows a milder inflammatory phenotype with altered T cell trafficking. These findings provide mechanistic insights and identify candidate immune signatures requiring validation in larger, aetiology‐specific cohorts.