International Journal of Infectious Diseases (Feb 2022)

Circulating level of sPD-1 and PD-1 genetic variants are associated with hepatitis B infection and related liver disease progression

  • Pham Thi Minh Huyen,
  • Dang Thi Ngoc Dung,
  • Peter Johann Weiß,
  • Phan Quoc Hoan,
  • Dao Phuong Giang,
  • Ngo Thi Uyen,
  • Nguyen Van Tuan,
  • Ngo Tat Trung,
  • Thirumalaisamy P. Velavan,
  • Le Huu Song,
  • Nghiem Xuan Hoan

Journal volume & issue
Vol. 115
pp. 229 – 236

Abstract

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ABSTRACT: Background: Programmed cell death-1 (PD-1) variants and circulating level of soluble PD-1 are associated with susceptibility to malignant and infectious disease. This study aimed to examine the association of PD-1.5 and PD-1.9 variants, and plasma sPD-1 level with hepatitis B virus (HBV) infection and disease progression. Methods: The study cohort consisted of adults infected with HBV (n=513) – stratified by clinical course, including chronic hepatitis B (CHB, n=173), liver cirrhosis (LC, n=134) and hepatocellular carcinoma (HCC, n=206) – and matched healthy controls (HC, n=196). The PD-1.5 (rs2227981 C/T) and PD-1.9 (rs2227982 C/T) genetic variants were genotyped by Sanger sequencing, and plasma sPD-1 levels were quantified by enzyme immunoassay. Results: Plasma sPD-1 levels were significantly higher among patients infected with HBV. The highest plasma sPD-1 levels were observed in patients with CHB, followed by patients with LC and HCC. In addition, the plasma sPD-1 levels correlated positively with liver inflammation [aspartate transaminase (AST): rho=0.57, P<0.0001; alanine aminotransferase: rho=0.57, P<0.0001], and were positively correlated with liver fibrosis [AST to platelet ratio index score: rho=0.53, P<0.0001). The PD-1.9 TT genotype was less common in patients with CHB compared with patients with LC, HCC, and HCC+LC in both codominant and recessive models (P<0.01), and was found to be a risk factor for HCC predisposition {HCC vs non-HCC: odds ratio (OR) 2.0 [95% confidence interval (CI) 1.13–3.7], Padj=0.017}. The PD-1.5 CT genotype was associated with reduced risk of acquiring HCC [OR 0.6 (95% CI 0.4–0.9), Padj=0.031]. Conclusion: sPD-1 level was associated with liver inflammation and progression of liver fibrosis, and the PD-1.5 and PD-1.9 variants were associated with HBV infection and progression of liver disease.

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