Soluble Programmed Cell Death-1: A Potential Predictor of HBsAg Loss in Pediatric Patients with Chronic Hepatitis B Undergoing Peginterferon Therapy.

Abstract

Purpose: Soluble programmed cell death-1 (sPD-1) level can predict hepatitis B surface antigen (HBsAg) loss in adult chronic hepatitis B (CHB) patients. However, whether sPD-1 level can serve as a potential seromarker for predicting HBsAg loss in pediatric patients remained to determine.

Patients and methods: Ninety-two pediatric HBeAg-positive CHB patients who received peginterferon (PegIFN) therapy with available serum samples were studied retrospectively. The average follow-up time was 45.0 months. Virological biomarkers and sPD-1 were serially measured.

Results: A total of 45 (48.9%) children achieved HBsAg loss at the end of treatment (EOT), and 84.4% (38/45) of them remained HBsAg-negative at the end of follow-up. At baseline, sPD-1 levels were comparable between patients who subsequently achieved HBsAg loss and those who did not (P = 0.217). However, a significantly more pronounced increase in sPD-1 levels was observed during PegIFN treatment in the HBsAg loss group (P_trend < 0.001). Consequently, at weeks 12, 24, and EOT, sPD-1 levels were significantly higher in children with HBsAg loss compared to those without (P < 0.001 at all time-points). In ROC curve analysis, sPD-1 had strong discriminatory ability for HBsAg loss at weeks 12 and 24, with area under ROC scores of 0.842 (95% CI, 0.744-0.946) and 0.863 (95% CI, 0.758-0.969), respectively, slightly lower than HBsAg but higher than HBV DNA.

Conclusion: Early on-treatment serum sPD-1 level has a potential predictive value for HBsAg loss in pediatric patients with HBeAg-positive CHB, which might provide a clue to optimize the management of PegIFN therapy. However, a prospective, multi-center study is warranted for further validation.