Circulating level of sPD-1 and PD-1 genetic variants are associated with hepatitis B infection and related liver disease progression. (February 2022)

• Record Type: Journal Article
• Authors: Huyen, Pham Thi Minh; Dung, Dang Thi Ngoc; Weiß, Peter Johann; Hoan, Phan Quoc; Giang, Dao Phuong; Uyen, Ngo Thi; Van Tuan, Nguyen; Trung, Ngo Tat; Velavan, Thirumalaisamy P.; Song, Le Huu; Hoan, Nghiem Xuan
• Is Part Of: International journal of infectious diseases. Volume 115(2022)
• Page Start: 229
• Page End: 236
• Publication Date: 2022-02
• Subjects: Hepatitis B virus -- Chronic hepatitis B -- Liver cirrhosis -- Hepatocellular carcinoma -- PD-1 -- sPD-1 -- PD-1.5 -- PD-1.9 polymorphism; Communicable diseases -- Periodicals; Communicable Diseases -- Periodicals; Communicable diseases; Periodicals; Electronic journals; 616.9
• DOI: 10.1016/j.ijid.2021.12.325
• Languages: English
• ISSNs: 1201-9712

Abstract

Highlights: PD-1/PD-L1 signalling involves T-cell exhaustion in patients with chronic hepatitis B virus (HBV) infection. Increased expression of PD-1 is considered to be associated with infectious diseases. PD-1.9 and PD-1.9 are associated with HBV-associated liver disease outcomes. Increased sPD-1 levels are associated with HBV-related liver inflammation and fibrosis. 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], P adj =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), P adj =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.