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

ABSTRACT

AIM: Differential 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. METHODS: We 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+ naïve 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). RESULTS: Several 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). CONCLUSIONS: Our results suggest that the analysis of peripheral memory T lymphocyte frequencies can noninvasively predict severe FIB and sensitively indicate the pathological progression of NAFLD.