title: Immune function biomarker QuantiFERON-monitor is associated with infection risk in cirrhotic patients.
abstract: OBJECTIVE
  To investigate whether a novel immune function biomarker QuantiFERON-Monitor (QFM) can identify cirrhotic patients at greatest risk of infection.
  
  
  METHODS
  Adult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47 (52%) transplanted on the day of their QFM. The remaining 44 (48%) were monitored for infections until transplant, death, or census date of 1stFebruary 2014.
  
  
  RESULTS
  Cirrhotic patients express a median QFM significantly lower than healthy controls (94.5 IU/mLvs423 IU/mL), demonstrating that they are severely immunosuppressed. Several factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient's immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13 (29.5%) experienced a pre-transplant infection a median 20 d (range 2-182) post-test. QFM < 214 IU/mL was associated with HR = 4.1 (P= 0.01) for infection. A very low QFM < 30 IU/mL was significantly associated (P= 0.003) with death in three patients who died while awaiting transplantation (HR = 56.6).
  
  
  CONCLUSIONS
  QFM is lower in cirrhotics, allowing objective determinations of an individual's unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection.
authors.affiliation: Siddharth Sood, Department of Gastroenterology and Hepatology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC 3050, Australia.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Sood
authors.affiliation: Siddharth Sood, Department of Gastroenterology and Hepatology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC 3050, Australia.
authors.forename: Lijia
authors.initials: L
authors.lastname: Yu
authors.affiliation: Siddharth Sood, Department of Gastroenterology and Hepatology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC 3050, Australia.
authors.forename: Kumar
authors.initials: K
authors.lastname: Visvanathan
authors.affiliation: Siddharth Sood, Department of Gastroenterology and Hepatology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC 3050, Australia.
authors.forename: Peter William
authors.initials: PW
authors.lastname: Angus
authors.affiliation: Siddharth Sood, Department of Gastroenterology and Hepatology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC 3050, Australia.
authors.forename: Paul John
authors.initials: PJ
authors.lastname: Gow
authors.affiliation: Siddharth Sood, Department of Gastroenterology and Hepatology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC 3050, Australia.
authors.forename: Adam Gareth
authors.initials: AG
authors.lastname: Testro
keywords: Biomarker; Cirrhosis; Immune dysfunction; Immune function; Immune system; Immunosuppression; Infection; Liver; Mortality