Circulating soluble programmed death-1 levels may differentiate immune-tolerant phase from other phases and hepatocellular carcinoma from other clinical diseases in chronic hepatitis B virus infection
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Na Li1,*, Zhihua Zhou1,*, Fang Li1, Jiao Sang1, Qunying Han1, Yi Lv2,3, Wenxuan Zhao1, Chunyan Li1 and Zhengwen Liu1,3
1Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
2Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
3Institute of Advanced Surgical Technology and Engineering, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
*These authors have contributed equally to this work
Zhengwen Liu, email: [email protected]
Keywords: hepatocellular carcinoma, hepatitis B virus, soluble PD-1, infection phases, clinical diseases
Received: December 12, 2016 Accepted: March 09, 2017 Published: May 02, 2017
Programmed death-1 (PD-1) is involved in the immune dysfunction of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study analyzed the association of circulating soluble PD-1 (sPD-1) levels with the phases and clinical diseases in chronic HBV infection. Serum sPD-1 levels were determined by enzyme linked immunosorbent assay in patients with different phases and liver diseases of chronic HBV infection. The sPD-1 levels in patients with chronic HBV infection were significantly elevated compared with HBV infection resolvers or healthy controls. According to phases, sPD-1 level in immune-tolerant phase (IT) was significantly lower than in other phases. Multivariate analysis showed that sPD-1 was an independent factor associated with IT. Area under the receiver operating characteristic (ROC) curves (AUC) showed that sPD-1 was significantly discriminative of IT from other phases with a cut-off of 1.535 ng/mL (AUC, 0.984; P<0.001). According to clinical diseases, sPD-1 level in HBV-related HCC was significantly higher than in other clinical diseases. Multivariate analysis showed that sPD-1 was an independent factor associated with HCC. The sPD-1 was significantly discriminative of HCC from other clinical diseases with a cut-off of 6.058 ng/mL (AUC, 0.962; P<0.001). The sPD-1 levels were significantly associated with HCC patients’ overall survival. HCC resection resulted in remarkable reduction in sPD-1 levels. These results demonstrate the involvement of sPD-1 in the disease course of chronic HBV infection and indicate the potential to apply sPD-1 as a biomarker for differentiating IT from other phases and HCC from other disease conditions in chronic HBV infection.
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