SPP1 and hepatocellular carcinoma: FISH confirmed stage-specific shifts in macrophage abundances and close spatial interactions between SPP1<sup>+</sup> macrophages and Tc in HCC specimens.<h4>Conclusion</h4>We provided a stage-resolved framework to delineated macrophage heterogeneity during CLDs progression and identified SPP1 and KLF2 as candidate prognostic biomarkers and potential therapeutic targets in HCC.