Soluble programmed death-1 is predictive of hepatitis B surface antigen loss in chronic hepatitis B patients after antiviral treatment

Abstract

BACKGROUND Hepatitis B surface antigen (HBsAg) loss, a functional cure in patients with chronic hepatitis B (CHB) undergoing antiviral therapy, might be an ideal endpoint of antiviral treatment in clinical practice. The factors that contribute to the functional cure remain unclear, and the predictors of functional cure are worth exploring. The concentration and kinetics of soluble programmed death-1 (sPD-1) in patients with CHB may play an important role in elucidating the immune response associated with functional cure after nucleos(t)ide analogs therapy. AIM To investigate the factors associated with HBsAg loss and explore the influence of sPD-1 Levels. METHODS This study analyzed the data and samples from patients with CHB who underwent antiviral treatment in a non-interventional observational study conducted at Peking University First Hospital in Beijing (between 2007 and 2019). All patients were followed up: Serum samples were collected every 3 mo during the first year of antiviral treatment and every 6 mo thereafter. Patients with positive hepatitis B e antigen levels at baseline and with available sequential samples who achieved HBsAg loss during antiviral treatment served as the case group. This case group ( n = 11) was further matched to 44 positive hepatitis B e anti patients without HBsAg loss as controls. The Spearman’s rank correlation test and receiver operating characteristic curves analysis were performed. RESULTS The sPD-1 Levels were higher in patients with HBsAg loss than in those without HBsAg loss from baseline to month 96, and the differences were significant between the groups at baseline ( P = 0.0136), months 6 ( P = 0.0003), 12 ( P < 0.0001), 24 ( P = 0.0007), 48 ( P < 0.0001), and 96 ( P = 0.0142). After 6 mo of antiviral treatment, the sPD-1 levels were positively correlated with alanine transaminase (ALT) levels ( r = 0.5103, P = 0.0017), and the sPD-1 levels showed apparent correlation with ALT ( r = 0.6883, P = 0.0192) and HBV DNA ( r = 0.5601, P = 0.0703) levels in patients with HBsAg loss. After 12 mo of antiviral treatment, the sPD-1 levels also showed apparent correlation with ALT ( r = 0.8134, P = 0.0042) and HBV DNA ( r = 0.6832, P = 0.0205) levels in patients with HBsAg loss. The sPD-1 levels were negatively correlated with HBsAg levels in all patients after 12 mo of antiviral treatment, especially at 24 ( r = -0.356, P = 0.0497) and 48 ( r = -...

Soluble Programmed Cell Death-1 is a Novel Predictor of HBsAg Loss in Chronic Hepatitis B Patients When Long-Term Nucleos(t)ide Analog Treatment is Discontinued

“…Consistent with a small scale study that high sPD-1 levels were predictive of HBsAg loss during treatment. 20 In the present study, detectable sPD-1 at EOT was negatively associated with clinical relapse and positively associated with subsequent HBsAg loss. The AUROC values for EOT sPD-1 were not perfect to predict clinical relapse and HBsAg loss, at 0.65 and 0.70, respectively.…”

“…15–17 However, very little research has assessed the concentration and kinetics of sPD-1 during chronic HBV infection. 18–22 Recently, Tan et al 20 showed that sPD-1 expression is associated with functional cure during NA therapy. However, the potential value of sPD-1 in patients with NA discontinuation is not well understood.…”