title: Longitudinal monocyte human leukocyte antigen-DR expression is a prognostic marker in critically ill patients with decompensated liver cirrhosis.
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)-gamma serum levels, tumour necrosis factor (TNF)-alpha ex 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-gamma 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-gamma 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.
authors.affiliation: Medical Department III, University Hospital Aachen, Aachen University, Aachen, Germany.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Berres
authors.forename: Barbara
authors.initials: B
authors.lastname: Schnyder
authors.forename: Eray
authors.initials: E
authors.lastname: Yagmur
authors.forename: Brett
authors.initials: B
authors.lastname: Inglis
authors.forename: Sven
authors.initials: S
authors.lastname: Stanzel
authors.forename: Jens J W
authors.initials: JJ
authors.lastname: Tischendorf
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.forename: Ron
authors.initials: R
authors.lastname: Winograd
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.forename: Hermann E
authors.initials: HE
authors.lastname: Wasmuth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D016638:Critical Illness; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007362:Intensive Care Units; D015850:Interleukin-6 / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood* / Q000401:mortality; D017093:Liver Failure / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006684:HLA-DR Antigens; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha