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Prediction of Fungal Infection Development and Their Impact on Survival Using the NACSELD Cohort

Bajaj, Jasmohan S MD, FACG1; Reddy, Rajender K MD2; Tandon, Puneeta MD3; Wong, Florence MD4; Kamath, Patrick S MD5; Biggins, Scott W MD6,7,20; Garcia-Tsao, Guadalupe MD8; Fallon, Michael MD9,10,20; Maliakkal, Benedict MD11,12,20; Lai, Jennifer MD13; Vargas, Hugo E MD14; Subramanian, Ram M MD15; Thuluvath, Paul MD16; Thacker, Leroy R PhD17; O'Leary, Jacqueline G MD18,19,20

American Journal of Gastroenterology: April 2018 - Volume 113 - Issue 4 - p 556–563
doi: 10.1038/ajg.2017.471

OBJECTIVES: Bacterial infections are associated with negative outcomes in cirrhosis but fungal infections are being increasingly recognized. The objective of this study is to define risk factors for fungal infection development and impact on 30-day survival.

METHODS: In a large, multi-center cirrhotic inpatient cohort, demographics, cirrhosis details, intensive care unit (ICU), organ failures/acute-on-chronic liver failure (ACLF), and 30-day survival were compared between patients without infections and with bacterial infections alone, with those with fungal infections. Variables associated with fungal infection development were determined using multi-variable regression. Ordinal variables (0=no infection, 1=community-acquired bacterial infection, 2=nosocomial bacterial, and 3=fungal infection) were input into a 30-day survival model.

RESULTS: A total of 2,743 patients (1,691 no infection, 918 bacterial, and 134 fungal infections) were included. Patients with fungal infection, all of which were nosocomial, were more likely to be admitted with bacterial infections, on spontaneous bacterial peritonitis prophylaxis, and have diabetes and advanced cirrhosis. Bacterial infection types did not predict risk for fungal infections. Multi-variable analysis showed male gender to be protective, whereas diabetes, longer stay, ICU admission, acute kidney injury (AKI), and admission bacterial infection were associated with fungal infection development (area under the curve (AUC)=0.82). Fungal infections were associated with significantly higher ACLF, inpatient stay, ICU admission, and worse 30-day survival. The case fatality rate was 30% with most fungal infections but >50% for fungemia and fungal peritonitis. On a multi-variable analysis, age, AKI, model for end-stage liver disease, ICU admission, and ordinal infection variables impaired survival (P<0.0001, AUC=0.83).

CONCLUSIONS: Fungal infections are associated with a poor 30-day survival in hospitalized cirrhotic patients compared with uninfected patients, and those with bacterial infections. Patients with diabetes, AKI, and those with an admission bacterial infection form a high-risk subgroup.

1Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA

2University of Pennsylvania, Philadelphia, Pennsylvania, USA

3University of Alberta, Edmonton, Alberta, Canada

4University of Toronto, Toronto, Ontario, Canada

5Mayo Clinic, Rochester, Minnesota, USA

6University of Colorado, Denver, Colorado, USA

7University of Washington, Seattle, Washington, USA

8Yale University, New Haven, Connecticut, USA

9University of Texas, Houston, Texas, USA

10University of Arizona, Phoenix, Arizona, USA

11University of Rochester, Rochester, New York, USA

12University of Tennessee, Memphis, Tennessee, USA

13University of California, San Francisco, California, USA

14Mayo Clinic, Scottsdale, Arizona, USA

15Emory University, Atlanta, Georgia, USA

16Mercy Medical Center, Baltimore, Maryland, USA

17Department of Biostatistics, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA

18Baylor University Medical Center, Dallas, Texas, USA

19Dallas VA Medical Center, Dallas, Texas, USA

Correspondence: Jasmohan S. Bajaj, MD, FACG, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, 1201 Broad Rock Boulevard, Richmond, Virginia 23249, USA. E-mail:

20These authors performed the work while in the affiliation first mentioned and have since moved to their second mentioned affiliation

published online 19 December 2017

SUPPLEMENTARY MATERIAL accompanies this paper at

Received 24 August 2017; accepted 2 November 2017

© The American College of Gastroenterology 2018. All Rights Reserved.
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