This sustained upregulation of SPHK1, along with elevated S1P levels, has been implicated in immune evasion through PD-L1–mediated T cell exhaustion in chronic HCV infection and to HCC progression post-SVR.23, 49, 50 Notably, Hamdane et al. reported that high SPHK1 expression has also been associated with increased HCC risk up to 10 years post-SVR23, while other studies reported significantly higher serum S1P levels in HCC patients compared with cirrhosis or healthy controls, highlighting their potential as diagnostic markers for HCC.50, 51. This evidence concerns the gene CD274 and hepatocellular carcinoma.