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Diminished non-classical monocytes in the blood associate with disease severity in alcoholic hepatitis

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Objective: Alcoholic hepatitis (AH) holds a high mortality, and vast macrophage infiltration of the liver is involved in the progressive liver injury. No efficient medical treatment exists, and macrophages may be a future treatment target. Here, we examine associations between non-classical monocyte subsets and cell surface markers of migration with disease activity in patients with severe AH. Methods: We analyzed samples from two cohorts of patients with AH. Cohort 1 included 15 AH patients, followed for 30 days, and 8 healthy controls (HCs). Cohort 2 included 23 AH patients, followed for 90 days, and 9 HCs. Peripheral blood mononuclear cells (PBMCs) from both cohorts were analyzed by flow cytometry. Liver biopsies from cohort 2 were analyzed by RNA sequencing. Results: Circulating non-classical monocytes in all but absent in patients with AH compared to HC in both cohorts (both p<0.0001). The frequency of non-classical monocytes was significantly associated with Maddrey’s discriminant function (mDF) (r=−0.79, p=0.0008, cohort 1), Child–Pugh score (CP) (r=−0.56, p=0.03, cohort 1), Model for End-Stage Liver Disease (MELD) (r=−0.54, p=0.02, cohort 2) and C-reactive protein (CRP) (r=−0.51, p=0.027, cohort 2). The surface expression of CD11b was increased on non-classical mono-cytes in patients with AH compared to HC (p<0.0001) (cohort 1). The mRNA expression of CD11b was increased in liver biopsies in patients with AH compared to HC (cohort 2) (p<0.0001). Conclusion: In this study, we describe an almost complete depletion of circulating non-classical monocytes in the blood in two independent cohorts of patients with AH, which may be associated with a possible harmful recruitment of these cells to the liver. These results contribute to a better understanding of the disease, which hopefully can lead to therapies that target the acute inflammatory response leading to severe AH.

OriginalsprogEngelsk
TidsskriftClinical and Experimental Gastroenterology
Vol/bind14
Sider (fra-til)259-267
Antal sider9
ISSN1178-7023
DOI
StatusUdgivet - 2021

Bibliografisk note

Publisher Copyright:
© 2021 Rasmussen et al.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

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