Soluble programmed death‐1 is a useful indicator for inflammatory and fibrosis severity in chronic hepatitis B

Abstract

SummaryElevated programmed death‐1 (PD‐1) has been found in immune cells in viral infections and plays an important role in infection persistence. The soluble form of PD‐1 (sPD‐1) is involved in tumours and viral infections. The aim of this study was to investigate the role of sPD‐1 in chronic hepatitis B (CHB). A total of two hundred and eighteen CHB patients and sixty healthy controls (HC) were enrolled. Demographic data and clinical parameters were collected. An ELISA assay was used to measure serum sPD‐1 levels, and the relationships between sPD‐1 and clinical/virological characteristics was analysed. sPD‐1 levels in CHB patients were higher (median 4.409 IQR 3.435‐5.306 pg/mL) than those of HC individuals (median 0.3665 IQR 0.2425‐0.5010 pg/mL). Among patients at various disease stages, patients with immune activity showed the highest sPD‐1 levels (median 5.138 IQR 4.329‐5.406 pg/mL). sPD‐1 concentration was associated with HBV markers (HBsAg, HBV DNA and HBeAg) and biochemical parameters (serum aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBil] and gamma glutamyl transferase [γ‐GT] levels) (all P < 0.05). sPD‐1 levels were higher in CHB patients with moderate‐to‐severe inflammation or fibrosis than in those with mild inflammation or fibrosis, regardless of ALT levels. The association between sPD‐1 and disease progression of CHB suggests that sPD‐1 could serve as a new indicator in assessing liver fibrosis. These findings may further aid in determining the initiation of antiviral treatment in patients with normal ALT levels.

Profiles of serum soluble programmed death‐1 and programmed death‐ligand 1 levels in chronic hepatitis B virus‐infected patients with different disease phases and after anti‐viral treatment

“…Therefore, we further analysed different disease phases of chronic HBV‐infected patients, which revealed that sPD‐1 and sPD‐L1 levels in ENI phase were lower than the other three phases, including EPI, ENH and EPH phases. These results were inconsistent with previous studies 14,25 . Our study found sPD‐1 level was positively correlated with HBV DNA load.…”

“…Consistent with most of previous studies, 14,25 using ultrasensitive multiplex immunoassays, we also found that serum sPD‐1 and sPD‐L1 levels were significantly elevated in chronic HBV infected‐patients compared to healthy controls. However, Yamagiwa et al concluded that the sPD‐L1 levels in CHB patients and HC were similar 26 .…”

“…Our study found sPD‐1 level was positively correlated with HBV DNA load. sPD‐1 levels in CHB patients have been confirmed associated with liver inflammation and fibrosis 25 . Patients in EPH and ENH phase have the characteristics of high HBV DNA load, high serum ALT levels, severe liver tissue inflammation, elevated sPD‐1 levels, activated T cell response to enhance virus clearance 16,17 .…”

Serum soluble programmed death ligand-1 is correlated with HBsAg level and nucleos(t)ide analogue therapy in chronic hepatitis B

“…The PD-1/PD-L1 axis as an immune checkpoint plays key role in the development and maintenance of persistent viral infection. Soluble PD-1 in serum has been found to be a useful indicator for inflammatory and fibrosis severity in CHB [27]. In this study, the serum sPD-L1 was also found to be meaningful in chronic HBV infection.…”

Discrepant range of sPD‐1 in different studies of chronic hepatitis B. A letter in response to Soluble programmed death‐1 is a useful indicator for inflammatory and fibrosis severity in chronic hepatitis B

“…We read with great interest the study by Zhou L et al focusing on the role of soluble programmed death-1 (sPD-1) in assessing liver fibrosis for chronic hepatitis B (CHB) patients. 1 However, several issues need to be clarified for better understanding the utility of sPD-1. First, the authors may need to check the range of the testing kit of sPD-1 (DuoSet Human PD-1, R&D systems, Minneapolis, MN, USA) in their manuscript.…”