Monocyte human leukocyte antigen - Antigen D related, neutrophil oxidative burst and cytokine analysis in patients of decompensated cirrhosis with and without acute-on chronic liver failure.

Sandeep Satsangi,Yogesh K. Chawla,Ajay Duseja,Shallu Tomer,Sunil K. Arora,Sunil Taneja,Radha K. Dhiman,Meenakshi Sachdeva,Juan Carlos Lopez-Delgado

doi:10.1371/journal.pone.0200644

Sandeep Satsangi, Yogesh K. Chawla + Show 7 more

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https://doi.org/10.1371/journal.pone.0200644

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Abstract

Background and aimDue to a dysregulated immune response, patients with acute-on-chronic liver failure (ACLF) have increased risk of infection and multi organ failure in comparison to compensated cirrhosis. The comparative data on the presence of ‘immune paresis’ in patients with ACLF and decompensated cirrhosis without ACLF is not available. Aim of the present study was to compare the immunological parameters in patients with decompensated cirrhosis with and without ACLF.MethodologyIn a prospective study, 76 patients with decompensated cirrhosis with (n = 38) and without (n = 38) ACLF and 10 healthy controls (HC) were evaluated for monocytic human leukocyte antigen–antigen D Related (HLA-DR) expression, mean density of HLA-DR expressed on the surface of these cells, neutrophil oxidative burst (NOB) capacity and serum levels of cytokines (IL-1, IL-6, IL-8, IL10, IL-12, and TNF-α).ResultsPatients of decompensated cirrhosis with and without ACLF demonstrated significantly lower mean percentage of monocytes expressing HLA-DR and quantitative increase in the NOB after stimulation with PMA when compared to HC. However there was no difference in mean percentage of monocytes with HLA-DR expression (43.61±26.56% vs. 43.10±20.98%) (p = 0.91), mean density of HLA-DR expression on the surface (30.34±29.32 vs. 41.71±52.13) (p = 0.42) and quantitative increase in NOB after stimulation with PMA (16.55±11.91 vs. 17.24±16.18) (p = 0.47) amongst patients with decompensated cirrhosis with and without ACLF. Patients with ACLF had significantly higher pro-inflammatory and anti-inflammatory cytokines in comparison to patients with decompensated cirrhosis without ACLF.ConclusionPatients with decompensated cirrhosis demonstrate a component of immune-paresis, however there is similar impairment in HLA–DR expression and NOB capacity in patients with and without ACLF. Both inflammatory and anti-inflammatory cytokines are increased in patients with ACLF in comparison to patients with decompensated cirrhosis without ACLF.

Highlights

Acute-on-chronic liver failure (ACLF) is an acute deterioration of known or unknown chronic liver disease (CLD) and has been defined by the Asia-Pacific Association for the Study of the Liver (APASL) as “acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed CLD.[1]
Patients of decompensated cirrhosis with and without acute-on-chronic liver failure (ACLF) demonstrated significantly lower mean percentage of monocytes expressing human leukocyte antigen–antigen D Related (HLA-DR) and quantitative increase in the neutrophil oxidative burst (NOB) after stimulation with Phorbol 12-myristate 13-acetate (PMA) when compared to healthy controls (HC)
There was no difference in mean percentage of monocytes with HLA-DR expression (43.61±26.56% vs. 43.10± 20.98%) (p = 0.91), mean density of HLA-DR expression on the surface (30.34±29.32 vs. 41.71±52.13) (p = 0.42) and quantitative increase in NOB after stimulation with PMA (16.55±11.91 vs. 17.24±16.18) (p = 0.47) amongst patients with decompensated cirrhosis

Summary

Introduction

Acute-on-chronic liver failure (ACLF) is an acute deterioration of known or unknown chronic liver disease (CLD) and has been defined by the Asia-Pacific Association for the Study of the Liver (APASL) as “acute hepatic insult manifesting as jaundice (defined as serum bilirubin level !5 mg/dL) and coagulopathy (define as international normalized ratio !1.5), complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed CLD.[1]. Even though ACLF is a rapid decompensation of cirrhosis, it differs from patients with decompensated cirrhosis without ACLF [ called chronic liver failure (CLF)] in many aspects. The development of hepatic failure and end-organ dysfunction in patients with ACLF is much faster than in patients with decompensated cirrhosis(CLF). A well defined precipitating event usually precedes the liver failure in ACLF.[3] Fourthly, unlike patients with CLF, in ACLF there is a component of multi-organ failure and increasing numbers of organ failures (i.e. renal, cerebral, circulatory, and pulmonary) portend progressively worse outcomes. Due to a dysregulated immune response, patients with acute-on-chronic liver failure (ACLF) have increased risk of infection and multi organ failure in comparison to compensated cirrhosis.

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