title: Upregulated Expression of A20 on Monocytes is Associated With Increased Severity of Acute-on-Chronic Hepatitis B Liver Failure: A Case-Control Study.
abstract: A20 expression is increased in various inflammatory diseases. However, the role of A20 in acute-on-chronic liver failure is unknown. This study was to evaluate A20 expression on monocytes and its associations with the severity of acute-on-chronic hepatitis B liver failure (ACHBLF). Thirty-seven patients with ACHBLF, 20 patients with chronic hepatitis B (CHB), and 15 healthy controls (HC) were enrolled in this case-control study. A20-positive monocytes were identified using flow cytometry. Serum levels of interleukin (IL)-10, IL-12p70, and TNF-α were determined using bead cytometry. A20 and IL-10 expressions were examined in THP-1 cells stimulated by lipopolysaccharide (LPS). The frequency of A20+ monocytes was significantly increased in patients with ACHBLF compared with HC (median [interquartile range, IQR]: 15.7 [22.8]% vs 2.5 [4.7]%, P < 0.001). Increased monocyte A20 expression was detected during the progression phase (including the mild/moderate and severe grades of ACHBLF) compared with patients in the recovery phase (both P < 0.05), and in the ACHBLF worsening group compared with patients in the improvement group (P < 0.001). LPS treatment upregulated A20 and IL-10 expressions in THP-1 cells. A20 expression on monocytes from patients with ACHBLF was positively correlated with total bilirubin (r = 0.60, P = 0.0001), direct bilirubin (r = 0.63, P < 0.0001), and MELD score (r = 0.43, P = 0.008), and inversely with prothrombin activity (r = -0.33, P = 0.046). IL-10 and TLR4 expression levels in monocytes, and serum levels of IL-10, IL-12p70, and TNF-α were increased in patients with ACHBLF compared with patients with CHB and HC. Increased A20 expression on monocytes was associated with the severity of ACHBLF.
authors.affiliation: From the Department of Infectious Diseases and Center for Liver Diseases, Tangdu Hospital, the Fourth Military Medical University, No. 569, Xinsi Road, Xi'an 710038, Shaanxi Province, China (YG, YH, YZ, YZ, YQ, CF, GJ, PZ, ZJ); and Department of Infectious Diseases, the Second Hospital, College of Medicine of Jiaotong University, No. 157, #5 West Road, Xi'an, Shaanxi, 710004, People's Republic of China (YG).
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Guo
authors.forename: Yu
authors.initials: Y
authors.lastname: He
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qin
authors.forename: Chao
authors.initials: C
authors.lastname: Fan
authors.forename: Guangxi
authors.initials: G
authors.lastname: Ji
authors.forename: Peixin
authors.initials: P
authors.lastname: Zhang
authors.forename: Zhansheng
authors.initials: Z
authors.lastname: Jia
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000276:immunology*; D000328:Adult; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D004268:DNA-Binding Proteins; C508609:IL10 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D018664:Interleukin-12; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3