title: Ascites bacterial burden and immune cell profile are associated with poor clinical outcomes in the absence of overt infection.
abstract: Bacterial infections, most commonly spontaneous bacterial peritonitis in patients with ascites, occur in one third of admitted patients with cirrhosis, and account for a 4-fold increase in mortality. Bacteria are isolated from less than 40% of ascites infections by culture, necessitating empirical antibiotic treatment, but culture-independent studies suggest bacteria are commonly present, even in the absence of overt infection. Widespread detection of low levels of bacteria in ascites, in the absence of peritonitis, suggests immune impairment may contribute to higher susceptibility to infection in cirrhotic patients. However, little is known about the role of ascites leukocyte composition and function in this context. We determined ascites bacterial composition by quantitative PCR and 16S rRNA gene sequencing in 25 patients with culture-negative, non-neutrocytic ascites, and compared microbiological data with ascites and peripheral blood leukocyte composition and phenotype. Bacterial DNA was detected in ascitic fluid from 23 of 25 patients, with significant positive correlations between bacterial DNA levels and poor 6-month clinical outcomes (death, readmission). Ascites leukocyte composition was variable, but dominated by macrophages or T lymphocytes, with lower numbers of B lymphocytes and natural killer cells. Consistent with the hypothesis that impaired innate immunity contributes to susceptibility to infection, high bacterial DNA burden was associated with reduced major histocompatibility complex class II expression on ascites (but not peripheral blood) monocytes/macrophages. These data indicate an association between the presence of ascites bacterial DNA and early death and readmission in patients with decompensated cirrhosis. They further suggest that impairment of innate immunity contributes to increased bacterial translocation, risk of peritonitis, or both.
authors.affiliation: Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Brisbane, Australia; Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Fagan
authors.affiliation: SAHMRI Infection and Immunity Theme, School of Medicine, Flinders University, Adelaide, Australia.
authors.forename: Geraint B
authors.initials: GB
authors.lastname: Rogers
authors.affiliation: Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Melino
authors.affiliation: Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Dionne M
authors.initials: DM
authors.lastname: Arthur
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Costello
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Morrison
authors.affiliation: Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Brisbane, Australia; Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Powell
authors.affiliation: Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Katharine M
authors.initials: KM
authors.lastname: Irvine
mesh_terms: D001202:Ascitic Fluid / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D004269:DNA, Bacterial / Q000737:chemistry*; D005260:Female; D005355:Fibrosis / Q000175:diagnosis / Q000382:microbiology*; D006801:Humans; D007113:Immunity, Innate; D008214:Lymphocytes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012336:RNA, Ribosomal, 16S / Q000737:chemistry
chemical_list: D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S