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.