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
ARTICLE HIGHLIGHTS
Research background

Opportunistic infection refers to any infection caused by a weakened immune system and typically does not occur in people with normal immune function. When they occur, patients presenting with opportunistic infections commonly display a significantly increased rate of morbidity and mortality. A number of studies have been conducted in Western countries and Japan to investigate the incidence of and risk factors for opportunistic infection in inflammatory bowel disease (IBD) patients. Currently, there are few epidemiological data on the rate of opportunistic infection in IBD patients in China. The risk factors for opportunistic infection in Chinese IBD patients remain unclear.

Research motivation

The main topics in our study are to predict the incidence of opportunistic infections related to IBD in China, and explore the risk factors for opportunistic infections. The key problems to be solved is to ensure compliance of enrolled IBD patients. The significance of solving these problems for future research in this field is to more accurately predict the incidence of and risk factors for opportunistic infections.

Research objectives

The main objectives in our study were to predict the incidence of opportunistic infections related to IBD in China, and explore the risk factors for opportunistic infections. The realized objectives include that the incidence of opportunistic infection in IBD patients in China is higher than that in Western countries and 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, according to our single-center study. The significance of realizing these objectives for future research in this field is to alert patients and physicians to pay attention to and prevent opportunistic infections. Meanwhile, our study can provide important information for clinicians and IBD patients in China and other countries.

Research methods

The research design that was adopted to realize the objectives is observational study and nested case-control study. Observational study is to observe and record the characteristics of research objects in a natural state, and describe and compare the results. In our study, the patients were followed for up to 12 mo to identify the incidence of infections. In nested case-control studies, cases and controls come from the same cohort, so the selection bias in effect estimation is reduced and comparability is good. For each infected IBD patient, two non-infected IBD patients were selected as controls in our study.

Research results

Our study found that the incidence of opportunistic infection in IBD patients in China is higher than that in Western countries and 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. Meanwhile, the use of infliximab alone does not increase the risk of opportunistic infection. Our findings remind patients and physicians to pay attention to and prevent opportunistic infections. As the genetic background, living environment, lifestyle, and diet of IBD patients in China are different from patients in Western countries, our study of opportunistic infection could provide important information for clinicians and IBD patients in China and other countries. The following problems remain to be solved: (1) Our study was a single-center clinical study, which cannot represent the situation of IBD patients in China as a whole; and (2) the sample size of this study for both ulcerative colitis and Crohn’s disease patients was small. A larger sample size would have allowed for more precise estimation of the incidence of opportunistic infections and increase in reliability of risk factors in Chinese IBD patients.

Research conclusions

The new findings of this study are that the incidence of opportunistic infection in IBD patients in China is higher than that in Western countries, according to our single-center study, and 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. Meanwhile, the use of infliximab alone does not increase the risk of opportunistic infection. The original insights into the current knowledge that this study offered is when opportunistic infection occurs, patients commonly display a significantly increased rate of morbidity and mortality. Therefore, prevention and identification of opportunistic infections are critical. The implications of this study for clinical practice in the future is patients and physicians need to pay attention to and prevent opportunistic infections.

Research perspectives

From this study, we can conclude that the incidence of opportunistic infection in IBD patients in China is higher than that in Western countries, and doctors should pay attention to and prevent the incidence of opportunistic infections. The future research direction is to conduct a multi-center study to evaluate the incidence of opportunistic infection in Chinese IBD patients, and more accurately screen out the risk factors leading to the occurrence of opportunistic infection in Chinese IBD patients, so as to effectively prevent the occurrence of opportunistic infection.