Retrospective Cohort Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 27, 2021; 13(11): 1777-1790
Published online Nov 27, 2021. doi: 10.4254/wjh.v13.i11.1777
Nonalcoholic fatty liver disease is associated with worse intestinal complications in patients hospitalized for Clostridioides difficile infection
Yi Jiang, Salil Chowdhury, Bing-Hong Xu, Mohamad Aghaie Meybodi, Konstantinos Damiris, Samanthika Devalaraju, Nikolaos Pyrsopoulos
Yi Jiang, Salil Chowdhury, Mohamad Aghaie Meybodi, Konstantinos Damiris, Samanthika Devalaraju, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101, United States
Bing-Hong Xu, Liver Center and Center for Asian Health, RWJBH-Saint Barnabas Medical Center, Florham Park, NJ 07932, United States
Nikolaos Pyrsopoulos, Department of Medicine, Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07101, United States
Author contributions: Jiang Y and Pyrsopoulos N planned and designed the study; Chowdhury S, Xu BH, Meybodi MA, Damiris K and Devalaraju S conducted the data collection and interpretation; Jiang Y, Chowdhury S, Xu BH, Damiris K and Devalaraju S contributed to the manuscript preparation; All authors contributed to the manuscript revisions, reviewed, and approved the final submitted manuscript.
Institutional review board statement: This retrospective cohort study did not directly involve any patients in the data collection process and the National Inpatient Sample (NIS) database is de-identified and available for the public. Therefore, Institutional Review Board approval was not required.
Conflict-of-interest statement: The authors have no conflicts of interest related to this publication.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at Participants gave informed consent for data sharing.
STROBE statement: The authors have read the STROBE Statement, and the manuscript was prepared and revised according to the STROBE Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Nikolaos Pyrsopoulos, FAASLD, AGAF, FACG, MD, PhD, Director, Professor, Department of Medicine, Gastroenterology and Hepatology, Rutgers New Jersey Medical School, 185 S. Orange Avenue, Medical Science Building H-536, Newark, NJ 07101, United States.
Received: June 14, 2021
Peer-review started: June 14, 2021
First decision: July 27, 2021
Revised: August 8, 2021
Accepted: September 19, 2021
Article in press: September 19, 2021
Published online: November 27, 2021

Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease with increasing prevalence worldwide. Clostridioides difficile infection (CDI) remains the most common cause of nosocomial diarrhea in developed countries.


To assess the impact of NAFLD on the outcomes of hospitalized patients with CDI.


This study was a retrospective cohort study. The Nationwide Inpatient Sample database was used to identify a total of 7239 adults admitted as inpatients with a primary diagnosis of CDI and coexisting NAFLD diagnosis from 2010 to 2014 using ICD-9 codes. Patients with CDI and coexisting NAFLD were compared to those with CDI and coexisting alcoholic liver disease (ALD) and viral liver disease (VLD), individually. Primary outcomes included mortality, length of stay, and total hospitalization charges. Secondary outcomes were in-hospital complications. Multivariate regression was used for outcome analysis after adjusting for possible confounders.


CDI with NAFLD was independently associated with lower rates of acute respiratory failure (2.7% vs 4.2%, P < 0.01; 2.7% vs 4.2%, P < 0.05), shorter length of stay (days) (5.75 ± 0.16 vs 6.77 ± 0.15, P < 0.001; 5.75 ± 0.16 vs 6.84 ± 0.23, P <0.001), and lower hospitalization charges (dollars) (38150.34 ± 1757.01 vs 46326.72 ± 1809.82, P < 0.001; 38150.34 ± 1757.01 vs 44641.74 ± 1660.66, P < 0.001) when compared to CDI with VLD and CDI with ALD, respectively. CDI with NAFLD was associated with a lower rate of acute kidney injury (13.0% vs 17.2%, P < 0.01), but a higher rate of intestinal perforation (P < 0.01) when compared to VLD. A lower rate of mortality (0.8% vs 2.7%, P < 0.05) but a higher rate of intestinal obstruction (4.6% vs 2.2%, P = 0.001) was also observed when comparing CDI with NAFLD to ALD.


Hospitalized CDI patients with NAFLD had more intestinal complications compared to CDI patients with VLD and ALD. Gut microbiota dysbiosis may contribute to the pathogenesis of intestinal complications.

Keywords: Nonalcoholic fatty liver disease, Clostridioides difficile infection, Gut microbiota, Intestinal complications, Alcoholic liver disease, Viral liver disease

Core Tip: This study demonstrated that patients hospitalized with Clostridioides difficile infection (CDI) and coexisting nonalcoholic fatty liver disease (NAFLD) had more favorable overall outcomes but higher rates of intestinal complications when compared to those with alcoholic liver disease and viral liver disease individually, which suggests altering gut microbiota may play an essential role in the pathogenesis of both CDI and NAFLD. NAFLD-associated metabolic syndrome may contribute significantly to gut dysbiosis and increase risk for CDI and its complications. This study provides potential directions for future prospective clinical research to identify the clinical meaningfulness of interactions between the gut microbiota, gut immunity and systemic inflammation.