Retrospective Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2025; 31(16): 104758
Published online Apr 28, 2025. doi: 10.3748/wjg.v31.i16.104758
Epstein-Barr virus infection is an independent risk factor for surgery in patients with moderate-to-severe ulcerative colitis
Hui Zhang, Xi Gu, Wei He, Shu-Liang Zhao, Zhi-Jun Cao
Hui Zhang, Shu-Liang Zhao, Zhi-Jun Cao, Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
Xi Gu, Wei He, Division of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
Co-first authors: Hui Zhang and Xi Gu.
Co-corresponding authors: Shu-Liang Zhao and Zhi-Jun Cao.
Author contributions: Zhang H and Gu X participated in the conceptualization, data acquisition and analysis, and drafted the manuscript; He W participated in the analysis of data and drafted the manuscript; Zhao SL and Cao ZJ contributed to the conceptualization, supervision; and funding, and revised the article; All authors contributed to the article and approved the final version to be submitted. Zhang H was responsible for patient screening, enrollment, collection of clinical data, performed data analysis and prepared the first draft of the manuscript. Gu X conducted EBV and CMV testing and assessment of the endoscopic biopsy or surgical specimens and contributed to the data analysis and manuscript preparation. Both Zhang H and Gu X have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper. Both Zhao SL and Cao ZJ have played important and indispensable roles in the study design, data interpretation and manuscript preparation as the co-corresponding authors. Zhao SL was instrumental and responsible for comprehensive literature search, data analysis and revised the manuscript. Cao ZJ applied for and obtained the funds for this research, conceptualized, designed, and supervised the whole process of the project and revised and submitted the manuscript. This collaboration between Zhao SL and Cao ZJ is crucial for the publication of this manuscript.
Supported by General Hospital Integrated Guidance Project of Shanghai Municipal Health Commission and Municipal Administration of Traditional Chinese Medicine (Phase I), No. ZXXT-202210; and "Science and Technology Innovation Action Plan" Medical Innovation Research Project of Shanghai Municipal Science and Technology Commission, No. 22Y11907900.
Institutional review board statement: This study was approved by the Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Ethical Committee No. LY2024-034-B, dated March 4, 2024).
Informed consent statement: The need for patient consent was waived due to the retrospective nature of the study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhi-Jun Cao, MD, PhD, Professor, Chief, Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 145 Middle Shandong Road, Shanghai 200001, China. caozj_renji@163.com
Received: December 31, 2024
Revised: March 18, 2025
Accepted: April 14, 2025
Published online: April 28, 2025
Processing time: 117 Days and 11 Hours
Abstract
BACKGROUND

Epstein-Barr virus (EBV) infection of the intestinal mucosa is associated with surgical risk in ulcerative colitis (UC); however, the exact effect remains unclear.

AIM

To determine whether EBV infection can predict the need for colectomy and to develop a surgical risk predictive model.

METHODS

This was a single-center retrospective study of 153 patients with moderate-to-severe UC between September 2012 and May 2023. EBV-encoded small RNA (EBER) in situ hybridization and immunohistochemistry (IHC) were used for EBV testing and assessment. Cytomegalovirus (CMV) was detected by IHC. Logistic regression analysis was conducted to identify risk factors for colectomy and develop a predictive risk model.

RESULTS

EBER-positivity in the intestinal mucosa was present in 40.4% (19/47) and 4.7% (5/106) of patients in the surgery and non-surgery groups, respectively, with significant differences between the groups (P < 0.01, odds ratio = 13.707). The result of multivariate logistic regression revealed that age, EBV infection in the colonic mucosa, CMV infection in the colonic mucosa, and treatment with three or more immunosuppressive agents before admission were significant independent predictors of colectomy. A nomogram incorporating these variables demonstrated good discriminative ability, and exhibited good calibration and clinical utility. IHC showed that EBV-infected cells mainly included B and T lymphocytes in patients with high EBER concentrations.

CONCLUSION

EBV infection of the intestinal mucosa is a significant independent risk factor for colectomy in patients with moderate-to-severe UC. The nomogram model, which includes EBV infection, effectively predicts colectomy risk.

Keywords: Epstein-Barr virus; Cytomegalovirus; Ulcerative colitis; Colectomy; Predictive model

Core Tip: This retrospective single-center observational study investigated the effect of Epstein-Barr virus (EBV) infection of the intestinal mucosa on surgical risk in patients with moderate-to-severe ulcerative colitis (UC). Surgical treatment remains necessary for patients refractory to medical therapy or with severe complications in patients with moderate-to-severe UC. Our study determined that EBV infection of the intestinal mucosa is a significant independent risk factor for colectomy in patients with moderate-to-severe UC. In addition, we developed a new nomogram model including EBV infection to help predict colectomy risk in patients with moderate-to-severe UC.