Beneficial effects of combination therapy after short term treatment. (A) Steatohepatitis and fibrosis were induced by CDAHFD (choline-deficient, amino acid-defined high-fat diet) over a total period of 8 weeks. Effects of pharmacologic treatment were assessed after administration of CCR2/CCR5 inhibitor (CCR2/5i) and/or PEG-FGF21 variant (FGF21v) over the last two weeks of injury induction. (B) Representative liver section of H&E, Sirius Red and F4/80 immunohistochemistry staining (×10 magnification; scale bars = 100 µm). (C,D) Serum alanine transaminase (ALT) levels, NAFLD activity score, hepatic triglyceride and hydroxyproline content as well as quantification of Sirius Red area fraction display the liver phenotype. (E,F) Quantification of F4/80 positive area fraction and flow cytometrically determined monocyte-derived macrophages (MoMFs) and liver Kupffer cells (KC). All data are presented as mean SD (n ≥ 6 per group) ns = non-significant, * p < 0.05, ** p < 0.01, *** p < 0.001 (one-way ANOVA with post-hoc testing).