My project is part of the larger cohort study MESSI, the Molecular Epidemiology of Severe Sepsis in the ICU. Some of the prime goals of MESSI are to establish a molecular cohort study of subjects presenting with sepsis or septic shock, and determine the association and potential utility of novel sepsis biomarkers. Sepsis is broad, and defined as a dysregulated host response to infection resulting in organ injury and is a leading cause of death, disability, and cost in the US. Clinical observations of sepsis from ICU doctors concur that patients with cirrhosis tend to have greater rates of sepsis, and the sepsis is generally worse. Considering cirrhosis is an acquired immunocompromised state with a predisposition to infections, this clinical observation is well justified. Prior studies have also found that cirrhosis is an independent risk factor for sepsis and sepsis-related mortality.

For this project, our goals were to understand sepsis characteristics of cirrhosis, the physiology of sepsis in patients with cirrhosis, and outcomes. Using data from the MESSI cohort, we defined the exposure as cirrhosis per patients’ history and physical forms, and considered outcomes of 30-day Mortality, ARDS by the Berlin Criteria, and AKI by the KDIGO Criteria. I utilized R programming to do the appropriate statistical analysis, which included Wilcoxon rank-sum tests, Pearson χ2 tests, and a multivariable logistic regression adjusting for the pre-specified confounders of age, race, and history of cancer, end-stage renal disease, hypertension, and coronary artery disease. 

We found cirrhosis is independently associated with greater mortality, AKI, and ARDS in sepsis. Furthermore, patients with cirrhosis who develop sepsis have distinct characteristics, including younger age, higher APACHE III scores, and greater end-stage renal disease. Sepsis in patients with cirrhosis is more commonly from abdominal/GI infections, while a lesser fraction is pneumonia. This finding was expected, as patients with cirrhosis commonly develop ascites, an accumulation of fluid in the abdominal cavity. Patients with cirrhosis also have greater physiologic abnormalities including lower MAP, higher WBCs, higher bilirubin, and higher creatinine. Future directions include biomarker analysis of endothelial, epithelial, and inflammatory markers to create targeted therapies for the prevention or treatment of organ failure.