CD274 and Cirrhosis: 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