Plasma Proteome to Look for Diagnostic Biomarkers of Early Bacterial Sepsis after Liver Transplantation

Abstract

Background While outcome continuously improves after liver transplantation, sepsis remains the leading cause of early postoperative mortality. Diagnosis of infections remains particularly difficult in these patients. This study used plasma profiling coupling Proteinchip array with surface-enhanced laser desorption ionization time-of-fly mass spectrometry to search for biomarkers of postoperative sepsis in patients who underwent liver transplantation. Methods Diagnosis of sepsis at day 5 relied on widely accepted clinical signs and positive culture of microbiologic samples. Profiles of day 5 plasma were obtained from SELDI-TOF CM10 chip (BioRad, Marnes-la-Coquette, France) analysis. Mean peak intensity of proteins was compared between septic and nonseptic plasma by U test followed by analysis of the area under the receiver-operating characteristic for the significant peaks. Diagnostic performance of significant proteins was established in a derivation set and in a validation set. Results In the derivation set of 31 patients with and 30 without infection, 23 plasma protein peaks were differentially expressed between patients with and without sepsis. Combination of five peaks allowed sepsis diagnosis with a positive likelihood ratio of 12.5 and a C-statistics of 0.72, 95% CI 0.57-0.85. In the validation set of 31 patients with infection and 34 without infection, the five peaks were differentially expressed as well and allowed day 5 sepsis diagnosis with a positive likelihood ratio of 5.1 and C-statistics of 0.74 (0.58-0.85). Conclusion A combination of five plasma protein peaks may provide material for useful diagnostic biomarkers of postoperative sepsis in patients undergoing liver transplantation. However, these proteins remain to be identified.