Fig. 3.

Representative examples of lipid and metabolite changes across fibrosis and steatosis and between NAFL/NASH states.

(A) Number of changing metabolites across Kleiner fibrosis stages in all (n = 627) participants, showing the number of metabolites changing between each stage (F1–F4) as compared with F0. (B) Venn diagram depicting which metabolites significantly change across fibrosis stages (light green) and steatosis grades (green) or between NAFL/NASH diagnoses (purple), revealing the existence of both overlapping and, crucially, specific metabolic signatures of 3 clinical perspectives of NAFLD. (C) Levels of lipids/metabolites across the 5 stages of fibrosis as per the Kleiner scoring system (bottom row), the 4 steatosis scores (top row), and between NAFL and NASH (middle row). For each row, 3 representative lipids and 1 metabolite are given. ANOVA and Tukey HSD p values shown in the upper left of each panel only given if they satisfy significance threshold of (p <0.05). Cer, ceramide; HSD, honest significant difference; LPC, lysophosphatidylcholine; NAFL, non-alcoholic fatty liver; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; SM, sphingomyelin; TG, triacylglycerol.