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Keywords:

  • cirrhosis;
  • critical illness;
  • HLA-DR;
  • immune paralysis

Abstract

Background: Critical illness in cirrhotic patients is associated with a poor prognosis and increased susceptibility to infections. Monocyte HLA-DR expression is decreased in cirrhotic patients, but its prognostic value has not been investigated prospectively.

Methods: Thirty-eight critically ill patients with decompensated liver cirrhosis were included in this prospective study. On admission to the intensive care unit (ICU), inflammatory parameters (C-reactive protein, procalcitonin and lipopolysaccharide-binding protein), interleukin (IL)-10, interferon (IFN)-γ serum levels, tumour necrosis factor (TNF)-αex vivo stimulation (whole blood assay) and HLA-DR expression on monocytes (FACS analysis) were determined. Immune parameters were furthermore measured every third day until discharge from the ICU or death of the patients.

Results: Intensive care unit mortality of the cirrhotic patients was 34.2%. During admission, TNF ex vivo, IFN-γ and HLA-DR expression were lower in non-survivors (all P<0.05), while IL-10 levels were increased in non-survivors compared with survivors (P=0.001). However, individual values clearly overlapped between groups. Prospective analysis revealed that monocyte HLA-DR expression remained stable or increased in survivors, but decreased in non-survivors (P=0.002). A decrease in HLA-DR expression between admission and day 3 was strongly associated with decreased IFN-γ levels and increased ICU mortality (hazard ratio 3.36, P=0.008), mostly owing to late sepsis. This association was independent of the sequential organ failure assessment and model for end-stage liver disease score.

Conclusions: Here we establish the relative HLA-DR expression (admission/day 3) as a prognostic marker for ICU mortality in critically ill cirrhotic patients. These results may guide the evaluation of immune-modulating therapies in these patients.