Loss of naive T lymphocytes is associated with advanced liver fibrosis in alcohol use disorder

Alcohol use disorder (AUD) is associated with changes in cellular immunity. The objective of the present study was to analyze the contribution of AUD to the differentiation of T cells and associations with advanced liver fibrosis (ALF).

This cross-sectional study included patients admitted for treatment of AUD between 2013 and 2016. T cell immune-phenotyping defined four profiles of cellular differentiation according to the expression of CCR7 and CD45RA: naive T cells, central memory (T_CM) cells, effector memory (T_EM) cells, and terminal effector (T_EMRA) cells. CD4⁺ memory cells were subdivided into Th1, Th2, and Th17 according to the expression of CXCR3 and CCR6. The stages of cellular differentiation were compared to healthy controls. ALF was defined as FIB-4 > 3.25.

Seventy-nine patients (81% men) with a median age of 50 years (IQR: 45-56 years) and median ethanol consumption of 150 g/day (IQR: 100-200 g/day) were included in the study. Compared to healthy controls, patients with AUD had fewer CD4⁺ naive cells (p < 0.001), more T_CM and T_EM cells (p = 0.003 and p = 0.050, respectively), and larger Th2 populations (p = 0.03). Among CD8⁺ cells, the percentage of T_CM, T_EM, and T_EMRA were higher in patients with AUD than in the healthy controls (p < 0.05). Patients with ALF had fewer CD4⁺ and CD8⁺ naive cells (p < 0.05) and more CD4⁺ memory cells than patients without ALF.

Altered lymphocyte differentiation in AUD patients suggests immunosenescence. An increase in memory cells and decrease in naive cells is associated with ALF.