Circulating programmed death-1 as a marker for sustained high hepatitis b viral load and risk of hepatocellular carcinoma e95870
Journal
PLoS ONE
Journal Volume
9
Journal Issue
11
Pages
e95870
Date Issued
2014
Author(s)
Cheng H.-Y.
Kang P.-J.
Wang Y.-H.
Jan M.-C.
Wu C.-F.
Lin C.-L.
Liaw Y.-F.
Lin S.-M.
Lee S.-D.
Abstract
Objective: Recent evidence indicates a crucial role of the immunoinhibitory receptor programmed death-1 (PD-1) in enforcing T-cell dysfunction during chronic viral infection and cancer. We assessed the impact of circulating soluble PD-1 (sPD-1) levels on long-term dynamics of hepatitis B virus (HBV) load and hepatocellular carcinoma (HCC) risk.Methods: In a case-cohort study on longitudinal analysis of viral load within a cohort of 2903 men chronically infected with HBV, followed up from baseline (1989-1992) through 2010, we determined sPD-1 levels in baseline plasma with enzymelinked immunosorbent assay from 126 men who subsequently developed HCC and 1155 men who did not develop HCC. To evaluate whether patients' characteristics involved the use of sPD-1 as a biomarker, sPD-1 was also tested in 614 newlydiagnosed patients with HBV-related HCC recruited from a multicenter study for comparison with the 1155 noncases in the case-cohort study.Results: Plasma quartile levels of sPD-1 were positively associated with HCC risk for men in the case-cohort analysis (vs. quartile 1: adjusted odds ratios [95% confidence intervals] for quartile 2-quartile 4 were 1.51 [0.75-3.03], 2.15 [1.12-4.13], and 2.29 [1.20-4.38], respectively), and in the case-control study regardless of age-of-onset and clinical stage. Furthermore, we found longitudinal effect of elevated sPD-1 levels to maintain higher viral load for 4 or more years, with greater and more prolonged effect among HBV genotype C- vs. non-C-infected participants. High levels of viral load and sPD-1 (vs. absence of both) was associated with a 6.29-fold increase in risk of HCC, and combining both conditions with HBV genotype C yielded an odds ratio of 30.47 with significant additive interaction (relative excess risk due to interaction: 27.08 [95% confidence interval58.76-45.41]).Conclusions: Our data suggest plasma sPD-1 as an important immune-related marker for assessment of HBV activity and HCC risk. ?heng et al.
SDGs
Other Subjects
alpha fetoprotein; hepatitis B surface antigen; programmed death 1 receptor; PDCD1 protein, human; programmed death 1 receptor; adult; aged; Article; cancer risk; cancer staging; cohort analysis; controlled study; hepatitis B; Hepatitis B virus genotype B; Hepatitis B virus genotype C; hepatitis C; human; liver cell carcinoma; liver cirrhosis; major clinical study; male; mixed infection; onset age; virus load; blood; Carcinoma, Hepatocellular; case control study; complication; Hepatitis B virus; Hepatitis B, Chronic; isolation and purification; Liver Neoplasms; middle aged; physiology; risk factor; virology; Adult; Aged; Carcinoma, Hepatocellular; Case-Control Studies; Cohort Studies; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Neoplasms; Male; Middle Aged; Programmed Cell Death 1 Receptor; Risk Factors; Viral Load
Type
journal article