LDHD and hepatocellular carcinoma: Functional validation included <i>in vitro</i> CCK8 and Transwell assays in Huh7 cells and <i>in vivo</i> xenograft experiments combining the LDHA inhibitor (R)-GNE-140 with a PD-1 antibody.<h4>Results</h4>Post-ICI, HCC cells upregulated pyruvate metabolism genes (LDHA, LDHB, LDHD) but showed decreased glycolysis, lactate buildup, reduced acetylation, and suppressed TCA cycle with AMPK activation.