Soluble form of CTLA‐4 is a good predictor for tumor recurrence after radiofrequency ablation in hepatocellular carcinoma patients

BACKGROUND: A soluble form of cytotoxic‐T‐lymphocyte‐antigen‐4 (sCTLA‐4) is a prognostic biomarker for several cancers but remains unclear in HCC patients. The aim of study is to evaluate the predictive role of serum sCTLA‐4 levels for tumor recurrence of chronic hepatis C (CHC)‐HCC patients receiving radiofrequency ablation (RFA). MATERIAL AND METHOD: A prospective study recruiting 88 CHC‐HCC patients was done between 2013 and 2019. Cox regression analysis was used to determine the predictors of early recurrence. All tests were two‐tailed, and the level of statistical significance was set as p < 0.05. RESULTS: During a median follow‐up of 44.4 months, 53 of the 88 (60.2%) CHC‐HCC patients encountered early recurrence within 2 years. The predictability of sCTLA‐4 for local recurrence (LR) and intrahepatic metastasis (IHM) by 2‐years using AUROC curve analysis were 0.740 and 0.715, respectively. Patients with high sCTLA‐4 levels (>9 ng/ml) encountered shorter recurrence‐free survival (RFS) for LR (log‐rank p = 0.017) but paradoxically longer RFS for IHM (log‐rank p = 0.007) compared to those with low levels (≤9 ng/ml). By multivariate Cox regression analysis, sCTLA‐4 levels and antiviral therapy were independent prognostic factor of early recurrence both in LR and IHM. A combination of baseline sCTLA‐4 and AFP level could improve the predictability of early LR and IHM with specificity of 80.0% and 79.7% and positive predictive value of 63.3% and 67.3%, respectively. CONCLUSIONS: sCTLA‐4 level is a good predictor for early HCC recurrence with higher levels indicating susceptibility to early LR, but protecting from early IHM.