Assessment of immune function and prediction of survival and infection in patients with severe alcoholic hepatitis: An exploratory study

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background and Aim</jats:title><jats:p>Alcoholic hepatitis (AH), a severe complication of long‐term alcohol misuse, has a 30% 90‐day mortality. Infections are common and associated with higher mortality. There is currently no accurate method to predict infection in these patients. We aimed to test a measure of immune function, the QuantiFERON Monitor (QFM), in predicting clinical outcomes in patients with severe AH.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Peripheral blood was taken at baseline, and QFM performed according to the manufacturer's instructions. In parallel, QFM samples were analyzed with a cytokine multiplex. Clinical outcomes of mortality at 28 and 90 days and development of infection were recorded prospectively.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Forty‐nine patients were recruited (mean age 51, 59% male and mean discriminant function 57.8). Interferon (IFN)‐γ release measured by standard QFM was significantly higher in survivors compared to non‐survivors at 28 (102 <jats:italic>vs</jats:italic> 16 IU/mL, <jats:italic>P</jats:italic> = 0.02) and 90 days (115 <jats:italic>vs</jats:italic> 32 IU/mL; <jats:italic>P</jats:italic> = 0.046). The area under the receiver operating characteristic curve (AUROC) was 0.79 for 28‐day mortality. IFN‐γ, IL‐10, and IL‐23 release measured by multiplex were significantly lower in patients who developed a subsequent infection compared to those who did not (115 <jats:italic>vs</jats:italic> 27 IU/mL, <jats:italic>P</jats:italic> = 0.037; 457 <jats:italic>vs</jats:italic> 202 pg/mL, <jats:italic>P</jats:italic> = 0.008; and 1039 <jats:italic>vs</jats:italic> 663 pg/mL, <jats:italic>p</jats:italic> = 0.01, respectively).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Immune dysfunction is associated with poorer outcomes in patients with severe AH. Measurement of IFN‐γ release by standard QFM accurately predicts early mortality, which can be applied to clinical practice as a biomarker of survival. Adaptation of the test to measure IL‐10 could be used as a biomarker of subsequent infection to guide clinical treatment decisions.</jats:p></jats:sec>