Wu Z, Huang ZW, Cao ZJ, Sun Y, Zhao XX, Xu WF, Chen SL, Zhang Y, Zhao SL. Risk factors and fatigue in difficult-to-treat Crohn’s disease: A cross-sectional study of a Chinese cohort. World J Gastroenterol 2026; 32(26): 118595 [DOI: 10.3748/wjg.118595]
Corresponding Author of This Article
Shu-Liang Zhao, MD, PhD, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, No. 160 Pujian Road, Pudong New Area, Shanghai 200001, China. zhaosl@sjtu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
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research-article
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Wu Z, Huang ZW, Cao ZJ, Sun Y, Zhao XX, Xu WF, Chen SL, Zhang Y, Zhao SL. Risk factors and fatigue in difficult-to-treat Crohn’s disease: A cross-sectional study of a Chinese cohort. World J Gastroenterol 2026; 32(26): 118595 [DOI: 10.3748/wjg.118595]
Zhi Wu, Zhi-Wei Huang, Zhi-Jun Cao, Ying Sun, Xin-Xian Zhao, Wen-Fang Xu, Sheng-Liang Chen, Shu-Liang Zhao, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200001, China
Yue Zhang, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Co-first authors: Zhi Wu and Zhi-Wei Huang.
Co-corresponding authors: Yue Zhang and Shu-Liang Zhao.
Author contributions: Wu Z drafted the article; Wu Z and Huang ZW performed the data analyses and contributed to the visualization as co-first authors; Wu Z, Cao ZJ, Chen SL, Zhang Y, and Zhao SL revised the article; Cao ZJ, Chen SL, and Zhao SL designed and supervised the study; Cao ZJ, Zhang Y and Zhao SL contributed to funding acquisition; Sun Y, Zhao XX and Xu WF collected the data; Zhang Y and Zhao SL contributed to statistical and analytic support as co-corresponding authors; and all authors have read and approved the final manuscript.
Supported by “Science and Technology Innovation Action Plan” Medical Innovation Research Project of Shanghai Municipal Science and Technology Commission, No. 22Y11907900.
Institutional review board statement: The study’s protocol was reviewed and approved by the Ethics Committee of Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital (No. LY2025-003-B).
Informed consent statement: Ethical approval for this retrospective cohort study was obtained with a waiver of informed consent.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
STROBE statement: The authors have read the STROBE Statement – checklist of items, and the manuscript was prepared and revised according to the STROBE Statement – checklist of items.
Data sharing statement: Data are available upon reasonable request.
Corresponding author: Shu-Liang Zhao, MD, PhD, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, No. 160 Pujian Road, Pudong New Area, Shanghai 200001, China. zhaosl@sjtu.edu.cn
Received: January 8, 2026 Revised: February 4, 2026 Accepted: April 2, 2026 Published online: July 14, 2026 Processing time: 170 Days and 4.9 Hours
Abstract
BACKGROUND
Fatigue is a prevalent and debilitating symptom in Crohn’s disease (CD). Recently, an international consensus proposed operative definitions for difficult-to-treat (DTT) inflammatory bowel disease. However, the risk factors for DTT-CD in the Chinese population and the relationship between fatigue and DTT-CD criteria remain unexplored.
AIM
To investigate the risk factors for DTT-CD in a Chinese cohort and investigate its association with fatigue.
METHODS
This single-center retrospective cohort study enrolled 175 CD patients from 2018 to 2024. DTT-CD was defined according to the consensus criteria of the International Organization for the Study of Inflammatory Bowel Diseases. Clinical characteristics, laboratory data, and fatigue assessed by the Multidimensional Fatigue Inventory were analyzed. Logistic and linear regression models were used to identify risk factors for DTT-CD and factors associated with fatigue.
RESULTS
Overall, 51.4% of patients met at least one DTT-CD criterion, with complex perianal disease being the most common (75.6%). Independent risk factors for DTT-CD included longer disease duration [odds ratio (OR) = 1.095, P = 0.014]; elevated interleukin (IL)-5 (OR = 2.715, P = 0.002) and IL-10 (OR = 1.234, P = 0.045); higher hemoglobin (OR = 1.025, P = 0.016); and need for partial enteral nutrition (PEN) (OR = 2.940, P = 0.017). DTT-CD patients had significantly higher mental fatigue scores than non-DTT-CD patients (P = 0.036). Among DTT-CD patients, fatigue was independently associated with partial enteral nutrition, diagnosis at age > 40 years, and surgical history. Factors related to the diagnosis of DTT-CD, such as complex perianal fistula and the number of treatment mechanisms, were not associated with fatigue across the total patient cohort.
CONCLUSION
DTT-CD, predominantly marked by complex perianal disease, is highly prevalent in these patients. Elevated IL-5 and IL-10 suggest a distinct immunophenotype in Chinese DTT-CD patients. Fatigue is associated with specific clinical features in DTT-CD patients.
Core Tip: This study applied the international difficult-to-treat (DTT) inflammatory bowel disease criteria to a Chinese cohort of Crohn’s disease (CD) patients. There was a high prevalence of DTT-CD, primarily driven by complex perianal disease. We identified elevated serum interleukin-5 and interleukin-10 as independent risk factors for DTT-CD even after adjustment for disease activity, suggesting a distinct immunophenotype. DTT-CD was associated with a significantly higher level of mental fatigue.
