Effect of elafibranor on NASH characteristic hallmarks. (A) Schematic representation of the anti‐NASH mechanism of elafibranor. (B) Representative images of neural lipid staining of NASH chips in (Bi) absence and (Bii) presence of elafibranor. (Biii) Difference in mean fluorescence intensity of neural lipid staining between NASH chips and NASH chips exposed to elafibranor. Data are presented as mean ± SEM; n ≥ 10. Significance was calculated by the nonparametric Mann‐Whitney test, ****P < 0.0001. (C) Effect of elafibranor on HSC activation. Representative images of HSCs under a NASH condition (Ci) without elafibranor exposure and (Cii) in the presence of elafibranor. (Ciii) Mean fluorescence intensity of α‐SMA‐stained HSCs in NASH chips in the absence and presence of elafibranor. Data are presented as mean ± SEM; n = 5. Significance was calculated by the nonparametric Mann‐Whitney test, **P < 0.01. (Civ) Average number of activated HSCs under a NASH condition without elafibranor exposure and in the presence of elafibranor after 10 days of disease induction. Data are presented as mean ± SEM; n = 6. Significance was calculated by the nonparametric Mann‐Whitney test, **P < 0.01. (D) Average number of ballooned HCs in control, NAFL, NASH, and NASH chips exposed to elafibranor. Data are presented as mean ± SEM; n ≥ 7. Significance was calculated using ANOVA followed by the Kruskal‐Wallis test, *P < 0.05 and ***P < 0.005. (E) Effect of elafibranor on expression levels of inflammatory and profibrotic markers of liver cells under a NASH condition. Concentration levels of inflammatory markers (Ei) MCP1, (Eii) MIP1α, and (Eiii) TNF‐α and profibrotic markers (Eiv) TGF‐β and (Ev) OPN in the effluent media of control, NASH, and NASH with elafibranor groups after 5 and 10 days of culturing. Data are presented as mean ± SEM; n = 3. Significance was calculated using two‐way ANOVA followed by the Bonferroni test, *P < 0.05, **P < 0.01, ***P < 0.005, and ****P < 0.0001. Abbreviations: AP‐1, activator protein 1; a.u., arbitrary units; conc., concentration; DAPI, 4′,6‐diamidino‐2‐phenylindole; PPRE, peroxisome proliferator response element.