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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.
Highlights
Infections are responsible for much of the morbidity, mortality and resource utilization in patients with decompensated cirrhosis[1,2]
Seven patients died with decompensated cirrhosis, the contribution of bacterial infections to their decompensation and
Bacterial infection is a major cause of early death in patients with cirrhosis
Summary
Infections are responsible for much of the morbidity, mortality and resource utilization in patients with decompensated cirrhosis[1,2]. Most commonly spontaneous bacterial peritonitis (SBP) in patients with ascites, occur in one-third of admitted patients with cirrhosis, and account for a 4-fold increase in mortality[3], but absence of clinical signs of infection is frequent and may delay diagnosis and treatment. A combination of 16S rRNA gene sequencing and quantitative PCR was recently used to show that ascitic fluid from cirrhotic patients comprises a continuum from low-level bacterial colonization in the absence of a neutrophil response, through to clinically significant and severe SBP[4]. The widespread detection of low levels of bacteria in ascites in the absence of peritonitis suggests first, that bacterial translocation to the peritoneal cavity is a common process, and second, that the entry of bacteria into this site may not be sufficient to give rise to SBP. Little is currently known about the role of ascites leukocyte composition and function in this context
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