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

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. 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. 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. 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.