Differential peripheral memory T cell subsets sensitively indicate the severity of nonalcoholic fatty liver disease

AimDifferential patterns of peripheral memory T cell subsets in nonalcoholic fatty liver disease (NAFLD) were assessed using flow cytometry (FCM) to elucidate their association with NAFLD severity and provide a new noninvasive method to sensitively detect the disease severity in addition to existing biomarkers.MethodsWe assessed the differential frequencies of peripheral memory T cell subsets in 103 patients with NAFLD according to the degree of liver fibrosis (FIB) using FCM analysis. We focused on the following populations: CCR7+ CD45RA+ naive T, CCR7+ CD45RA- central memory T cells (TCM), CCR7- CD45RA- effector memory T, and CCR7- CD45RA+ terminally differentiated effector memory T (TEMRA) cells in CD4+ and CD8+ T, Th1, Th2, and Th17 cells, respectively. To evaluate the pathological progression of the disease, these frequencies were also examined according to the degree of the NAFLD activity score (NAS).ResultsSeveral significant correlations were observed between laboratory parameters and peripheral memory T lymphocyte frequencies according to the degree of liver FIB and NAS in NAFLD. In univariate and multivariate analyses, the frequency of CD8+ TEMRA cells predicted severe FIB, and the predictive power was validated in an independent cohort. Furthermore, the frequencies of several memory T cell subsets sensitively indicated the pathological progression of NAFLD (Th17 TCM: steatosis, CD4+ TCM: lobular inflammation, and CD8+ TEMRA and effector memory T cells: hepatocellular ballooning).ConclusionsOur results suggest that the analysis of peripheral memory T lymphocyte frequencies can noninvasively predict severe FIB and sensitively indicate the pathological progression of NAFLD. The analysis of peripheral memory T lymphocyte frequencies can noninvasively sensitively detect nonalcoholic fatty liver disease (NAFLD) severity in addition to existing biomarkers. We should focus on CD8+ terminally differentiated effector memory T cells as a predictor of severe fibrosis and also on CD8+ effector memory T cells, and CD4+ and Th17 central memory T cells as indicators of the pathological progression of NAFLD.image