Expression of CD38+CD8+ T cells in hepatitis B-related acute-on-chronic liver failure and its prognostic value

Immune dysfunction plays a critical role in the progression of acute-on-chronic liver failure (ACLF), inducing severe systemic inflammation, aggravating multi-organ failure, and finally manifests as jaundice and coagulopathy with the development of a high 28-day mortality. There is an urgent need for new and accurate prognostic biomarkers to validate the dynamic and timely changes of immune function in ACLF patients. Here we explored the potential role of CD38, an immunoregulatory molecule, in predicting the prognosis of HBV related ACLF. The study enrolled 30 chronic hepatitis B patients, 72 HBV-related cirrhosis patients, and 58 HBV-ACLF patients. Flow cytometry analysis was used to evaluate the expression of CD38 on subtypes of immnue cells from peripheral blood mononuclear cell from the above individuals. Multiple cytokine levels wer measured by ELISA analysis to identify the severity of systemic inflammation. Compared with B cells or NK cells, specific CD38highCD8+ T cells is highly consistent with MELD and Child-Pugh scores, served as promising marker as a sign of hepatic injury (was positively associated with bilirubin, AST/ALT ratio), and inversely with indicative markers of hepatic compensatory capability (e.g., platelet count). Our analysis of cytokine levels revealed that CD38 likely modulates immune responses by regulating cytokine profiles, shaping the immune microenvironment, and playing a role in the clinical features of HBV-ACLF. Notably, the CD38highCD8+ T cells also served as a potential indicator to distinguish between clinical recovery and deterioration of ACLF, with a higher proportion of CD38 high expression indicating poorer prognosis and lower expression indicating better prognosis. Univariate regression analysis further identified the mean fluorescence intensity of CD38 in CD8+ T cells as an independent prognostic predictor at both 28 days and 3 months. We further Integrate the counts of CD38+CD8+T cells with the MELD score substantially enhances prognostic accuracy (AUC = 0.859, 95% CI 0.745–0.973, p < 0.001). Our findings advocate for the use of CD38 expression on CD8+ T cells as a biomarker of immune status and prognostic indicator in HBV-ACLF, proposing its combination with the MELD score as a refined tool for clinical prognostic assessment.