Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change

Abstract

Natural killer (NK) cells play a therapeutic role in liver fibrosis (LF). We aimed to analyze NK cells in heavy drinkers without cirrhosis or decompensated liver disease and establish correlations with other related subpopulations. Data on sociodemographic characteristics, alcohol consumption, laboratory parameters, and immunophenotyping of NK (CD16+/CD56+), T (CD3+), B (CD19+), NKT (CD16+/CD56+/CD3+), and cytotoxic (CD3-CD8+) cells were collected. Fibrosis-4 (FIB-4) scores were used to compare patients without (FIB-4 < 1.45) and with (FIB-4 > 3.25) advanced LF (ALF). We included 136 patients (76% male) with a mean age of 49 years who had a 15-year alcohol use disorder (AUD) and alcohol consumption of 164 g/day. Patients with ALF (n = 25) presented significantly lower absolute total lymphocyte, T cell, B cell, and NKT cell numbers than patients without LF (n = 50; p < 0.01). However, the NK cells count was similar (208 ± 109 cells/µL vs. 170 ± 105 cells/µL) in both groups. The T cells percentage was lower (80.3 ± 5.6% vs. 77 ± 7%; p = 0.03) and the NK cells percentage was higher (9.7 ± 5% vs. 13 ± 6%; p = 0.02) in patients with ALF than in those without LF. The percentages of NK cells and T cells were inversely correlated in patients without (r = –0.65, p < 0.01) and with ALF (r = −0.64; p < 0.01). Additionally, the NK cells and CD3-CD8+ cell percentages were positively correlated in patients without (r = 0.87, p < 0.01) and with (r = 0.92; p < 0.01) ALF. Conclusions: Heavy drinkers without decompensated liver disease showed an increase in NK cells related to T cells lymphopenia and an increase in cytotoxic populations. The interaction of NK cells with other subpopulations may modify alcohol-related liver disease progression.