Jasmohan S Bajaj1, Hugo E Vargas2, K Rajender Reddy3, Jennifer C Lai4, Jacqueline G O'Leary5, Puneeta Tandon6, Florence Wong7, Robert Mitrani3, Melanie B White8, Megan Kelly2, Andrew Fagan8, Rohan Patil9, Shaimaa Sait9, Masoumeh Sikaroodi9, Leroy R Thacker8, Patrick M Gillevet9. 1. Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia. Electronic address: jasmohan.bajaj@vcuhealth.org. 2. Mayo Clinic, Scottsdale, Arizona. 3. University of Pennsylvania, Philadelphia, Pennsylvania. 4. University of California, San Francisco, California. 5. Baylor University Medical Center, Dallas, Texas; Dallas VA Medical Center, Dallas, Texas. 6. University of Alberta, Edmonton, Alberta, Canada. 7. University of Toronto, Toronto, Ontario, Canada. 8. Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia. 9. Microbiome Analysis Center, George Mason University, Manassas, Virginia.
Abstract
BACKGROUND & AIMS: Inpatients with cirrhosis are prone to develop acute-on-chronic liver failure (ACLF). ACLF is associated with dysbiosis of the intestinal microbiota, which might serve as a prognostic factor. We investigated whether features of the intestinal microbiota associate organ failure, transfer to intensive care, and mortality within 30 days in patients admitted to the hospital with cirrhosis. METHODS: Stool samples were collected from 181 patients with cirrhosis (age 56 years; mean model for end-stage liver disease score, 21; 43% with infections) at time of admission, from multiple hospitals in North America. Patients were followed for 30 days for development of ACLF, extra-hepatic organ failures, and death or hospice care. Microbiota were analyzed by 16s rRNA sequencing for alpha diversity (within groups), beta diversity (between groups), cirrhosis dysbiosis ratio (CDR), and taxa that differed between groups with vs without negative outcomes (individual organ failures, transfer to intensive care, ACLF, death, or hospice). Regression analyses were performed using microbial and clinical variables for each outcome. RESULTS: ACLF developed in 8% of study subjects; 16% were transferred to intensive care and 21% died. Beta diversity of the intestinal microbiome was significantly different, whereas alpha diversity was similar, between subjects with vs without outcomes. The CDR was lower in subjects who developed ACLF, especially among those with renal failure. Taxa belonging to phylum Proteobacteria (Enterobacteriaceae, Campylobacteriaceae, and Pasteurellaceae) and Firmicutes (Enterococcaceae and Streptococcaceae) were associated with development of negative outcomes, whereas other Firmicutes members (Lachnospiraceae and Clostridiales) reduced risk of negative outcomes. Changes in the microbiota associated with extra-hepatic organ failure, transfer to intensive care, ACLF, and death, independently on logistic regression analyses. CONCLUSION: In hospitalized patients with cirrhosis, dysbiosis of the intestinal microbiota on admission (particularly changes in Protebacteria constituents) associates with increased risk of extra-hepatic organ failure, ACLF, and death, independent of clinical factors. Strategies to reduce gut dysbiosis might improve outcomes of patients with cirrhosis.
BACKGROUND & AIMS: Inpatients with cirrhosis are prone to develop acute-on-chronic liver failure (ACLF). ACLF is associated with dysbiosis of the intestinal microbiota, which might serve as a prognostic factor. We investigated whether features of the intestinal microbiota associate organ failure, transfer to intensive care, and mortality within 30 days in patients admitted to the hospital with cirrhosis. METHODS: Stool samples were collected from 181 patients with cirrhosis (age 56 years; mean model for end-stage liver disease score, 21; 43% with infections) at time of admission, from multiple hospitals in North America. Patients were followed for 30 days for development of ACLF, extra-hepatic organ failures, and death or hospice care. Microbiota were analyzed by 16s rRNA sequencing for alpha diversity (within groups), beta diversity (between groups), cirrhosis dysbiosis ratio (CDR), and taxa that differed between groups with vs without negative outcomes (individual organ failures, transfer to intensive care, ACLF, death, or hospice). Regression analyses were performed using microbial and clinical variables for each outcome. RESULTS: ACLF developed in 8% of study subjects; 16% were transferred to intensive care and 21% died. Beta diversity of the intestinal microbiome was significantly different, whereas alpha diversity was similar, between subjects with vs without outcomes. The CDR was lower in subjects who developed ACLF, especially among those with renal failure. Taxa belonging to phylum Proteobacteria (Enterobacteriaceae, Campylobacteriaceae, and Pasteurellaceae) and Firmicutes (Enterococcaceae and Streptococcaceae) were associated with development of negative outcomes, whereas other Firmicutes members (Lachnospiraceae and Clostridiales) reduced risk of negative outcomes. Changes in the microbiota associated with extra-hepatic organ failure, transfer to intensive care, ACLF, and death, independently on logistic regression analyses. CONCLUSION: In hospitalized patients with cirrhosis, dysbiosis of the intestinal microbiota on admission (particularly changes in Protebacteria constituents) associates with increased risk of extra-hepatic organ failure, ACLF, and death, independent of clinical factors. Strategies to reduce gut dysbiosis might improve outcomes of patients with cirrhosis.
Authors: Jasmohan S Bajaj; Jacqueline G OʼLeary; Puneeta Tandon; Florence Wong; Guadalupe Garcia-Tsao; Patrick S Kamath; Scott W Biggins; Jennifer C Lai; Hugo E Vargas; Benedict Maliakkal; Michael B Fallon; Paul J Thuluvath; Ram M Subramanian; Leroy R Thacker; K Rajender Reddy Journal: Am J Gastroenterol Date: 2019-07 Impact factor: 10.864
Authors: Jasmohan S Bajaj; Andrew Fagan; Melanie B White; James B Wade; Phillip B Hylemon; Douglas M Heuman; Michael Fuchs; Binu V John; Chathur Acharya; Masoumeh Sikaroodi; Patrick M Gillevet Journal: Am J Gastroenterol Date: 2019-07 Impact factor: 10.864