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16 November 2018

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Int J Med Sci 2017; 14(5):403-411. doi:10.7150/ijms.18784

Research Paper

Increase of Soluble Programmed Cell Death Ligand 1 in Patients with Chronic Hepatitis C

Satoshi Yamagiwa1✉, Toru Ishikawa2, Nobuo Waguri3, Soichi Sugitani4, Kenya Kamimura1, Atsunori Tsuchiya1, Masaaki Takamura1, Hirokazu Kawai1, Shuji Terai1

1. Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan;
2. Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan;
3. Department of Gastroenterology and Hepatology, Niigata City General Hospital, Niigata 950-1197, Japan;
4. Department of Gastroenterology and Hepatology, Tachikawa General Hospital, Nagaoka 940-8621, Japan.


Objectives: To determine whether 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.

Methods: We investigated the 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. Serum was also obtained from 22 patients with chronic hepatitis B (CHB) and from 10 healthy donors (HC). The sPD-L1 levels were measured using an ELISA kit. In addition, we examined the PD-L1 expression on the cell surface of immortalized hepatocytes (HPT1) after incubation with cytokines, including IFN-γ.

Results: The pretreatment serum sPD-L1 levels were significantly increased 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). No significant differences in the sustained virological response (SVR) rates were found between the TVR- (85.0%, n=40) and SMV-treated (80.0%, n=40) groups, and the pretreatment levels of serum sPD-L1 were not significantly different 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). The pretreatment level of sPD-L1 was positively correlated 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, we confirmed that PD-L1 expression was induced after stimulation with IFN-γ.

Conclusions: In this study, we first found that sPD-L1 was increased in patients with CHC. Our results indicate that the level of serum sPD-L1 might be associated with the progression of CHC and the generation of hepatocellular carcinoma.

Keywords: soluble programmed cell death ligand 1, programmed cell death 1, chronic hepatitis C, Telaprevir, Simeprevir.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
How to cite this article:
Yamagiwa S, Ishikawa T, Waguri N, Sugitani S, Kamimura K, Tsuchiya A, Takamura M, Kawai H, Terai S. Increase of Soluble Programmed Cell Death Ligand 1 in Patients with Chronic Hepatitis C. Int J Med Sci 2017; 14(5):403-411. doi:10.7150/ijms.18784. Available from