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Increase of soluble programmed cell death ligand 1 in patients with chronic hepatitis C

International Journal of Medical Sciences Sep 19, 2017

Yamagiwa S, et al. - This study aimed at assessing if the soluble programmed cell death ligand 1 (sPD-L1) levels in patients with chronic hepatitis C (CHC) are associated with the clinical features of the disease and the efficacy of treatment, including interferon (IFN)-α. Findings revealed increased sPD-L1 levels in patients with CHC. The level of serum sPD-L1 could be related with the progression of CHC and the generation of hepatocellular carcinoma.

Methods

  • An investigation was conducted of sPD-L1 levels in the sera of 80 genotype 1b Japanese patients with CHC who underwent 12 weeks of telaprevir (TVR)- or simeprevir (SMV)-based triple therapy followed by 12 weeks of dual therapy with pegylated IFN-α plus ribavirin.
  • The authors also obtained serum from 22 patients with chronic hepatitis B (CHB) and from 10 healthy donors (HC).
  • Using an ELISA kit, they measured the sPD-L1 levels.
  • In addition, the PD-L1 expression on the cell surface of immortalized hepatocytes (HPT1) after incubation with cytokines, including IFN-γ was assessed.

Results

  • Significant increase in pretreatment serum sPD-L1 levels was observed in patients with CHC (median 109.3 pg/ml, range 23.1-402.3) compared with patients with CHB (69.2 pg/ml, 15.5-144.8; P <0.001) and HC (100.3 pg/ml, 40.1-166.6; P = 0.039).
  • There appeared no significant differences in the sustained virological response (SVR) rates between the TVR- (85.0%, n=40) and SMV-treated (80.0%, n=40) groups; the pretreatment levels of serum sPD-L1 differed not markedly between patients who achieved SVR (105.0 pg/ml, 23.1-402.3) and non-SVR patients (133.5 pg/ml, 39.9-187.2; P = 0.391).
  • There appeared a positive correlation of pretreatment level of sPD-L1 with the alanine aminotransferase and alpha-fetoprotein levels (R2= 0.082, P = 0.016, and R2 = 0.149, P = 0.002, respectively).
  • Although immortalized hepatocytes do not express PD-L1, it was confirmed that PD-L1 expression was induced after stimulation with IFN-γ.

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