Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2019; 25(18): 2240-2250
Published online May 14, 2019. doi: 10.3748/wjg.v25.i18.2240
Nested case-control study on risk factors for opportunistic infections in patients with inflammatory bowel disease
Shan-Shan Gong, Yi-Hong Fan, Qing-Qing Han, Bin Lv, Yi Xu
Shan-Shan Gong, Yi-Hong Fan, Qing-Qing Han, Bin Lv, Yi Xu, Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
Author contributions: Gong SS conducted clinical observation, analyzed the data, and wrote the paper; Fan YH designed the research and revised the paper; Han QQ collected the data; Xu Y and Lv B conducted literature search and provided valuable suggestions for this study; all authors have read and approved the final manuscript.
Supported by: National Natural Science Foundation of China, No. 81473506; Natural Science Foundation of Zhejiang Province, No. LY16H290001 and No. LY17H290009; Project of Department of Construction of Zhejiang Province, No. WKJ-ZJ-1531; and Zhejiang TCM Science and Technology Project, No. 2016ZB047 and No. 2017ZA056.
Institutional review board statement: This study was approved by the institutional review board of First Affiliated Hospital of Zhejiang Chinese Medical University.
Informed consent statement: Informed consent was obtained from each patient.
Conflict-of-interest statement: The authors have declare no conflicts of interest.
Data sharing statement: No additional data are available.
STROBE statement: The manuscript was prepared according to the STROBE checklist.
Open-Access: This 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 Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Yi-Hong Fan, MD, PhD, Associate Professor, Chief Doctor, Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54, Youdian Road, Shangcheng District, Hangzhou 310006, Zhejiang Province, China. yhfansjr@163.com
Telephone: +86-571-87608001 Fax: +86-571-87608001
Received: February 22, 2019
Peer-review started: February 22, 2019
First decision: March 5, 2019
Revised: March 11, 2019
Accepted: March 29, 2019
Article in press: March 30, 2019
Published online: May 14, 2019
Processing time: 82 Days and 2 Hours
Abstract
BACKGROUND

When opportunistic infections occur, patients with inflammatory bowel disease (IBD) commonly display a significantly increased rate of morbidity and mortality. With increasing use of immunosuppressive agents and biological agents, opportunistic infections are becoming a hot topic in the perspective of drug safety in IBD patients. Despite the well-established role of opportunistic infections in the prognosis of IBD patients, there are few epidemiological data investigating the incidence of opportunis-tic infections in IBD patients in China. Besides, the risk factors for opportunistic infection in Chinese IBD patients remain unclear.

AIM

To predict the incidence of opportunistic infections related to IBD in China, and explore the risk factors for opportunistic infections.

METHODS

A single-center, prospective study of IBD patients was conducted. The patients were followed for up to 12 mo to calculate the incidence of infections. For each infected IBD patient, two non-infected IBD patients were selected as controls. A conditional logistic regression analysis was used to assess associations between putative risk factors and opportunistic infections, which are represented as odds ratios (OR) and 95% confidence intervals (CIs).

RESULTS

Seventy (28.11%) out of 249 IBD patients developed opportunistic infections. Clostridium difficile infections and respiratory syncytial virus infections were found in 24 and 16 patients, respectively. In a univariate analysis, factors such as the severity of IBD, use of an immunosuppressant or immunosuppressants, high levels of fecal calprotectin, and C-reactive protein or erythrocyte sedimentation rate were individually related to a significantly increased risk of opportunistic infection. Multivariate analysis indicated that the use of any immunosuppressant yielded an OR of 3.247 (95%CI: 1.128-9.341), whereas the use of any two immunosuppressants yielded an OR of 6.457 (95%CI: 1.726-24.152) for opportunistic infection. Interestingly, when immunosuppressants were used in combination with infliximab (IFX) or 5-aminosalicylic acid, a significantly increased risk of opportunistic infection was also observed. The relative risk of opportunistic infection was greatest in IBD patients with severe disease activity (OR = 9.090; 95%CI: 1.532-53.941, relative to the remission stage). However, the use of IFX alone did not increase the risk of opportunistic infection.

CONCLUSION

Factors such as severe IBD, elevated levels of fecal calprotectin, and the use of immunosuppressive medications, especially when used in combination, are major risk factors for opportunistic infections in IBD patients. The use of IFX alone does not increase the risk of opportunistic infection.

Keywords: Nested case-control study; Opportunistic infections; Inflammatory bowel disease

Core tip: When opportunistic infections occur, patients with inflammatory bowel disease (IBD) commonly display a significantly increased rate of morbidity and mortality. With increasing use of immunosuppressive agents and biological agents, opportunistic infections are becoming a hot topic in the perspective of drug safety in IBD patients. Despite the well-established role of opportunistic infections in the prognosis of IBD patients, there are few epidemiological data investigating the incidence of opportunistic infections in IBD patients in China. Besides, the risk factors for opportunistic infections in Chinese IBD patients remain unclear.