Mitochondrial Membrane Potential of CD8+ T Cells Predicts Bacterial Infection and Rapid Development of Acute-on-chronic Liver Failure in Cirrhotic Patients.

Abstract

Background and aims: Patients with cirrhosis are at an increased risk of bacterial infection (BI), which is the most common precondition for acute-on-chronic liver failure (ACLF). In this study, we aimed to evaluate the ability of mitochondria-related indicators (mitochondrial mass and mitochondrial membrane potential (MMP)) of T cells in peripheral blood to predict BI and ACLF within 90 days in cirrhotic patients.

Methods: We prospectively studied mitochondria-related indicators in various T cells from 235 cirrhotic patients at the Second Hospital of Nanjing. The outcomes of interest were BI and ACLF.

Results: The restricted cubic spline analysis showed that the MMP of CD8⁺ T cells had a linear relationship with the risk of BI and ACLF (both P < 0.001). Multivariable Cox regression analysis demonstrated that the MMP of CD8⁺ T cells was an independent risk factor for both BI and ACLF (BI: hazard ratio 0.96, 95% confidence interval 0.94-0.98; P < 0.001; ACLF: hazard ratio 0.94, 95% confidence interval 0.90-0.97; P < 0.001). The MMP of CD8⁺ T cells exhibited better diagnostic efficacy than traditional indices in predicting BI (C index: 0.75). The MMP of CD8⁺ T cells, when combined with traditional models (Child-Turcotte-Pugh and model for end-stage liver disease score), improved their diagnostic efficiency in predicting both BI and ACLF. Additionally, the MMP of CD8⁺ T cells showed a significant negative correlation with inflammation-related markers (P < 0.05). Mitochondrial damage and abnormally activated mitochondrial autophagy were observed in CD8⁺ T cells from cirrhotic patients with low MMP.

Conclusions: The MMP of CD8⁺ T cells could serve as a valuable predictor of BI and ACLF within 90 days in cirrhotic patients.