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Related Experiment Video

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Hepatic CD4 T Cells Predict Hepatocellular Carcinoma Risk on Metabolic Dysfunction-Associated Steatohepatitis

Emilse Rodriguez1, Peter Simon2, Sabrina Dhooge3

  • 1Hospital Privado Centro Médico de Córdoba S.A., Córdoba, Argentina.

United European Gastroenterology Journal
|December 12, 2025
PubMed
Summary

Increased CD4+ T cell infiltration in the liver predicts hepatocellular carcinoma (HCC) development in patients with metabolic dysfunction-associated steatohepatitis (MASH). Combining immune cell data with clinical factors offers strong predictive value for high-risk MASH patients.

Keywords:
CD4+ T cellsHCCINRMASHPD1/PDL1 interactionsblood‐based biomarkers

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Area of Science:

  • Hepatology
  • Immunology
  • Oncology

Background:

  • Metabolic dysfunction-associated steatohepatitis (MASH) is a growing cause of liver cancer.
  • Understanding the immune microenvironment in MASH is crucial for predicting hepatocellular carcinoma (HCC) development.

Purpose of the Study:

  • To characterize inflammatory infiltrates in liver biopsies of MASH patients who developed HCC versus controls.
  • To identify predictive immune signatures associated with MASH-induced HCC progression.

Main Methods:

  • Analysis of liver biopsies from MASH patients (pre-HCC and control) using multiplexed immunohistochemistry.
  • Single-cell RNA-seq to characterize hepatic CD4+ T cell heterogeneity.
  • Evaluation of clinical parameters including liver function tests and platelet counts.

Main Results:

  • Pre-HCC MASH showed altered inflammatory distribution compared to controls.
  • Significantly higher CD4+ T cell and CD4+PD1+ cell densities were observed in pre-HCC MASH patients.
  • A combination of immune cell data and clinical variables achieved high predictive performance (AUC=0.944) for HCC development.

Conclusions:

  • Increased liver CD4+ T cell infiltration is a key feature of MASH progression to HCC.
  • Immune signatures combined with clinical parameters can effectively identify MASH patients at high risk for HCC.