Prospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 18, 2016; 8(35): 1569-1575
Published online Dec 18, 2016. doi: 10.4254/wjh.v8.i35.1569
Immune function biomarker QuantiFERON-monitor is associated with infection risk in cirrhotic patients
Siddharth Sood, Lijia Yu, Kumar Visvanathan, Peter William Angus, Paul John Gow, Adam Gareth Testro
Siddharth Sood, Department of Gastroenterology and Hepatology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC 3050, Australia
Siddharth Sood, Peter William Angus, Paul John Gow, Adam Gareth Testro, Liver Transplant Unit Victoria, University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia
Lijia Yu, Kumar Visvanathan, Innate Immune Laboratory, University of Melbourne, St Vincent’s Hospital, Fitzroy, VIC 3065, Australia
Author contributions: Sood S and Testro AG designed the research, recruited participants, performed the research and wrote the paper; Yu L and Visvanathan K performed the research; Angus PW and Gow PJ analysed the data and helped write the paper.
Institutional review board statement: Approval was granted from the Austin Human Research Ethics Committee prior to this study being undertaken.
Clinical trial registration statement: As an observational study, this trial was not prospectively registered.
Informed consent statement: All study participants, or their legal guardian, provided informed consent prior to study enrolment.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Siddharth Sood, MBBS, BMedSci, PhD, Head of Hepatology, Department of Gastroenterology and Hepatology, University of Melbourne, Royal Melbourne Hospital, Royal Parade, Parkville, VIC 3050, Australia.
Telephone: +61-3-93427470 Fax: +61-3-93427848
Received: July 12, 2016
Peer-review started: July 14, 2016
First decision: September 7, 2016
Revised: October 6, 2016
Accepted: October 22, 2016
Article in press: October 24, 2016
Published online: December 18, 2016

To investigate whether a novel immune function biomarker QuantiFERON-Monitor (QFM) can identify cirrhotic patients at greatest risk of infection.


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 1st February 2014.


Cirrhotic patients express a median QFM significantly lower than healthy controls (94.5 IU/mL vs 423 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).


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.

Keywords: Infection, Biomarker, Immune dysfunction, Immune function, Immunosuppression, Liver, Immune system, Cirrhosis, Mortality

Core tip: QuantiFERON-Monitor (QFM) is a net immune function biomarker that measures interferon-γ after stimulation of the innate and adaptive immune systems and is based on a readily available pathology platform. Measuring QFM in cirrhotic patients provides an objective marker of their immune dysfunction, which has otherwise been difficult to quantify. Low QFM is significantly associated with the risk of pre-transplant infection, and very low QFM may be associated with increased risk of mortality.