Markers of activated inflammatory cells are associated with disease severity and intestinal microbiota in adults with non­alcoholic fatty liver disease.

ABSTRACT

Several mechanisms contribute to the pathogenesis of non­alcoholic fatty liver disease (NAFLD). The intestinal microbiota (IM) and liver immune cells (LIC) may serve a role, but there has been no previous study assessing potential associations between IM and LIC. The aim of the present study was to investigate whether there are differences in LIC markers between patients with NAFLD and healthy controls (HC), and to determine whether these markers are associated with specific IM. The present prospective, cross­sectional study examined a cohort of adults with liver biopsy­confirmed NAFLD and HC. Clinical and laboratory data were collected. Fecal IM was assessed by quantitative polymerase chain reaction and LIC, by immunohistochemistry. NAFLD activity score (NAS) was used for disease severity. Liver immune cell counts were increased in patients with NAFLD (n=34) vs. HC (n=8) and this was associated with disease severity. Hematopoietic cell marker cluster of differentiation (CD)45+ and Kupffer cell marker CD163+ were higher in NAFLD compared with HC, and those with an NAS ≥5 had higher levels of CD20+ cells, a marker of B cells, vs. a NAS of 0 or 1­4. Additionally, from those patients (5 HC, 34 NAFLD), IM was measured. Specific immune cells in portal or lobular areas correlated with specific fecal IM, suggesting a potential association between IM and liver inflammation in patients with NAFLD. Specifically, Faecalibacterium prausnitzii was negatively correlated with CD45+ (r= ­0.394; P=0.015) and CD163+ (r= ­0.371; P=0.022) cells in the portal tract and Prevotella was negatively correlated with CD20+ (r= ­0.353; P=0.028) cells in the liver lobule. Other taxa exhibited no correlation. In conclusion, the present study demonstrated a potential association between IM and liver inflammation in NAFLD.