Leucocyte ratios are biomarkers of mortality in patients with acute decompensation of cirrhosis and acute‐on‐chronic liver failure

Abstract

Background:In patients with cirrhosis, progression to acute decompensation (AD) and acute-on-chronic liver failure (ACLF) has been associated with poor prognosis. Differential leucocyte ratios might predict mortality in systemic inflammatory conditions. Aim:To evaluate differential leucocyte ratios as prognostic biomarkers in patients with cirrhosis.Methods: Patients with AD and ACLF were recruited from four centres in three countries. Peripheral blood differential leucocytes were measured (three centres using flow cytometry) on hospital admission and at 48 hours. Ratios were correlated to model for end-stage liver disease (MELD), chronic liver failure-sequential organ failure (CLIF-SOFA), suspected/culture-positive bacterial infection and survival.Results: Nine hundred twenty-six patients (562 (61%) male, median age 55 (25-94) years) were studied. Overall, 350 (37%) did not survive to hospital discharge.Neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR) were elevated in patients with AD and ACLF who died during their hospital stay. On multivariate analysis NLR retained statistical significance independently of CLIF-SOFA or MELD. NLR >30 was associated with an 80% 90-day mortality in patients with ACLF but not AD. On sensitivity analysis for subgroups (alcohol-related liver disease and suspected sepsis), NLR and MLR retained statistically robust accuracy for the prediction of mortality. Significant predictive accuracy was only observed in centres using flow cytometry. Conclusion:Leucocyte ratios are simple and robust biomarkers of outcome in ACLF, which are comparable to CLIF-SOFA score but dependent on leucocyte quantification method. NLR and MLR may be used as screening tools for mortality prediction in patients with acutely deteriorating cirrhosis.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction

“…127 HNA-1 and HNA-2 are also significantly increased in patients with decompensated cirrhosis and ACLF compared to heathy volunteers. 128 Ex vivo HNA-1, but not HNA-2, induces an intense in vitro inflammatory response from peripheral blood mononuclear cells (114). Overall, these results suggest that oxidised albumin can be included among the factors that promote systemic inflammation in decompensated cirrhosis and ACLF and may provide clues to guide albumin administration in these settings.…”

“…and increasing neutrophil and monocyte to lymphocyte ratios predict death in patients with acute decompensation and ACLF. 114 If the innate immune system is persistently stimulated, especially during disease progression and with disease duration, neutrophils and monocytes/macrophages switch into a tolerogenic and non-responsive phenotype. Immune paralysis has been primarily observed in sepsis but also develops in patients with acute decompensation and ACLF.…”

Editorial: outcome prediction in patients with cirrhosis and acute‐on‐chronic liver failure—authors' reply

“…We thank Alexpopolou and Vasilieva for their comments 1 on our article regarding the benefit of using leucocyte ratios for the prediction of outcome in acute decompensation (AD) and acute‐on‐chronic liver failure (ACLF) 2 in patients with cirrhosis 3 . We agree that the ready availability of counting cells by flow cytometry would make these ratios attractive for use in many centres in many countries.…”

Baseline Neutrophil-to-Lymphocyte Ratio Is Independently Associated With 90-Day Transplant-Free Mortality in Patients With Cirrhosis

“…Neutrophil-to-lymphocyte ratio reflects a systemic inflammatory response and shows a significant independent correlation with advanced inflammation diseases (e.g., severe alcoholic hepatitis and non-alcoholic fatty liver diseases) ( 9 , 10 ). In patients with severe end-stage liver diseases (e.g., ACLF), NLR was identified as an effective biomarker for hospital mortality prediction ( 11 ). A previous study reported that increased NLR independently predicted the short-term mortality in cirrhotic patients with AD ( 12 ).…”