OC-009 Progression of cirrhotic liver disease towards acute-on-chronic liver failure decompensation triggers changes in innate immune cell phenotype and their response to pro-inflammatory stimuli. (17th June 2017)

• Record Type: Journal Article
• Authors: Maini, AA; China, L; Gilroy, DW; O'Brien, A
• Is Part Of: Gut. Volume 66(2017)Supplement 2
• Page Start: A5
• Page End: A5
• Publication Date: 2017-06-17
• Subjects: Cirrhosis complication -- Decompensated liver disease -- innate immune system -- Liver cirrhosis; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2017-314472.9
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Introduction: Bacterial infection is a major cause of hospital admission in liver cirrhosis and patients are highly prone to nosocomial infection. Innate immune dysfunction is implicated in these patients. As there are no current strategies to reverse immune dysfunction, antibiotics are liberally used to treat patients in an era of increasing anti-microbial resistance. We aimed to determine whether progression to ACLF triggers a change in the receptor phenotype on innate immune cells reflecting impaired function. We also explored the response to inflammatory stimuli. Any changes in profile may reveal novel targets for immune therapy. Method: Peripheral whole blood of healthy volunteers (HV), ambulant outpatients attending for drainage of ascites and acute decompensated (AD) cirrhotic patients was studied. Cells were analysed by flow cytometry for activation and cell type. Whole blood was stimulated ex vivo with 1 ng/ml lipopolysaccharide for 4 hours. Supernatants were analysed for cytokines. Cells were analysed by flow cytometry. Results: Neutrophils demonstrated a significant decrease in CD88 (p=0.0006) from HV to ACLF, with decreasing trends of CD11b, CD54, CD66b and significant increases in CD62L (p=0.0298) observed as disease severity increased. When stimulated with LPS, increases in CD11b (p<0.0001), CD54 (p=0.0287) and CD66b (p=0.0340) were reduced in ACLF compared to HV. These observations were not seen in ambulant patients however trends in each marker were seen in the same direction as ACLF. In mononuclear phagocytes HLA-DR was significantly reduced between HV and both ambulant (p=0.0019) and ACLF (p<0.0001), and CD88 between HV and ACLF (p=0.0083). There were also trends of increased CD16, CD62L and CD64, with decreasing CD11b and CD54. When stimulated, there was a significant increases in CD64 (p=0.0004), and increasing trends in CD11b, CD54, CD32 and CD88 in ACLF patients, as well as a failure to increase HLA-DR. A significant difference was also observed between HV and ambulant patients in CD64 (p=0.0297), with trends in the other markers mirroring the ALCF patients but to a lesser degree. TNF levels in the supernatants of the stimulated blood were reduced in both ambulant and AD patients compared to HV. Conclusion: The phenotype of innate immune cells in ACLF was altered reflecting immune dysfunction and potentially explaining increased rates of bacterial infection. The response of innate cells to stimulation was also modified. These changes reflect a markedly reduced bactericidal and phagocytic potential of these cells. This is mirrored by the reduced production of TNF-a by whole blood stimulation. Overall, we see an immune-fatigued phenotype in innate immunity. Disclosure of Interest: None Declared