Soluble Programmed Cell Death-1 Predicts Hepatocellular Carcinoma Development During Nucleoside Analogue Treatment

Abstract

Soluble immune checkpoint molecules are emerging novel mediators of immune regulation. However, it is unclear whether soluble immune checkpoint proteins affect the development of hepatocellular carcinoma (HCC) during nucleos(t)ide analogue (NA) treatment in patients with chronic hepatitis B virus infection. This study included 122 NA-naïve patients who received NA therapy. We assessed the associations of clinical factors, including soluble immune checkpoint proteins, with HCC development during NA treatment. The baseline serum concentrations of 16 soluble immune checkpoint proteins were measured using multiplexed fluorescent bead-based immunoassay. In total, 13 patients developed HCC during the follow-up period (median duration, 4.3 years). Of the 16 proteins, soluble inducible T-cell co-stimulator (≥ 164.71 pg/mL; p = 0.014), soluble programmed cell death-1 (sPD-1) (≤ 447.27 pg/mL; p = 0.031), soluble CD40 (≤ 493.68 pg/mL; p = 0.032), and soluble herpes virus entry mediator (≤ 2,470.83 pg/mL; p = 0.038) were significantly associated with HCC development (log-rank test). In a multivariate analysis, an sPD-1 level ≤ 447.27 pg/mL (p = 0.014; hazard ratio [HR], 4.537) and α-fetoprotein level ≥ 6.4 ng/mL (p = 0.040; HR, 5.524) were independently and significantly associated with HCC development. sPD-1 is a novel predictive biomarker for HCC development during NA treatment.

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

“…36 Supporting this, several studies have shown that high serum sCTLA-4 levels predicted shorter RFS in patients with glioma 21 and colorectal cancer. 22 As for the hepatocellular carcinoma, Kozuca et al 37 tried to elucidate the associations of 16 soluble immune checkpoint proteins including sCTLA-4 with HCC development during nucleos(t)ide analogue (NA) treatment in 122 chronic hepatitis B (CHB) patients, However, there was no significant correlation between sCTLA-4 and HCC development. Nevertheless, when consider the tumor recurrence, we have now shown in this study serum sCTLA-4 level is associated with tumor recurrence in CHC-HCC patients with high sCTLA-4 levels had shorter RFS for early LR.…”