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World J Gastroenterol. Dec 14, 2026; 32(46): 123374
Published online Dec 14, 2026. doi: 10.3748/wjg.123374
Clinical features and biomarkers associated with ulcerative colitis: A systematic review and meta-analysis
Kai Liu, Xiao-Han Zhang, Xiang-Yu Zhou, Yu-Xuan Liu, Shi-Qi Pan, Ting-Xiu Liu, Robb Russell, Xue-Hui Wang, Yu-Pu Yao, Xing-Jie Zhao, Hui-Yi Sun, Chuan-Lan Ju, Jian-Ping Liu, Zhao-Lan Liu
Kai Liu, Xiao-Han Zhang, Ting-Xiu Liu, Jian-Ping Liu, Zhao-Lan Liu, Center for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
Xiang-Yu Zhou, Yu-Xuan Liu, Shi-Qi Pan, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
Robb Russell, Southern California University of Health Sciences, Whittier, CA 90604, United States
Xue-Hui Wang, Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing 100029, China
Yu-Pu Yao, Xing-Jie Zhao, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China
Hui-Yi Sun, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
Chuan-Lan Ju, Department of Public Health, Yantai Hospital of Traditional Chinese Medicine, Yantai 264000, Shandong Province, China
Jian-Ping Liu, Center for Evidence-Based Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
Co-first authors: Kai Liu and Xiao-Han Zhang.
Author contributions: Liu K and Zhang XH contributed equally, as they are co-first authors; Liu K designed the study, was responsible for formal analysis, and revised the manuscript; Zhang XH designed the study, was responsible for data curation, and wrote and revised the manuscript; Zhou XY and Liu YX contributed to data curation, validated the data, and revised the manuscript; Pan SQ and Liu TX contributed to data curation, and revised the manuscript; Russell R, Wang XH, Yao YP, Zhao XJ, Sun HY, and Ju CL interpreted the data and revised the manuscript; Liu JP and Liu ZL supervised the study, and revised the manuscript; all authors reviewed and approved the final version of the manuscript.
AI contribution statement: The authors declare that no generative AI or AI-assisted technologies were used in the preparation of this manuscript.
Supported by The National Natural Science Foundation of China, No. 82374298.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Zhao-Lan Liu, PhD, Professor, Center for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, No. 11 East Road of North Third Ring Road, Chaoyang District, Beijing 100029, China.
lzl1019@163.com
Received: May 18, 2026
Revised: July 19, 2026
Accepted: September 4, 2026
Published online: December 14, 2026
Processing time: 157 Days and 10.7 Hours
BACKGROUND
Diagnosing ulcerative colitis (UC) remains a clinical challenge due to overlapping presentation with other intestinal disorders. While endoscopy serves as the reference standard, its routine application for initial assessment is constrained by its invasiveness. Improved recognition of non-invasive indicators associated with UC could facilitate timely patient stratification, but their association strengths relative to differential diagnoses have not been systematically quantified.
AIM
To systematically quantify the association strengths of clinical features and biomarkers with UC relative to its differential diagnoses.
METHODS
PubMed, EMBASE, Web of Science, the Cochrane Library, and four Chinese databases were systematically searched from inception up to October 15, 2025. Eligible studies evaluated the association strengths of clinical features and biomarkers with UC vs other differential diagnoses. Pooled odds ratios (ORs) and mean differences (MDs) were calculated as the primary outcomes using a random-effects model. Heterogeneity was evaluated through subgroup analyses, and sensitivity analyses were conducted by omitting high-risk studies and employing generalized linear mixed models.
RESULTS
Across 389 studies, bloody mucopurulent stools showed a strong positive association with UC vs intestinal tuberculosis [OR = 43.14, 95% confidence interval (CI): 5.75-323.92]. Conversely, perianal fistulas were inversely associated with UC vs Crohn’s disease (OR = 0.08, 95%CI: 0.04-0.14). Fecal calprotectin distinguished UC from irritable bowel syndrome (MD = 696.31 μg/g, 95%CI: 512.38-880.23), while perinuclear anti-neutrophil cytoplasmic antibodies were strongly associated with UC vs Crohn’s disease (OR = 8.70, 95%CI: 6.70-11.31). Comparing active UC with disease remission, fecal calprotectin (MD = 387.04 μg/g, 95%CI: 292.55-481.54) and C-reactive protein (MD = 12.94 mg/L, 95%CI: 10.48-15.41) were significantly elevated.
CONCLUSION
This meta-analysis systematically quantifies the multidimensional clinical and laboratory association strengths with UC, establishing a non-invasive framework that facilitates pre-endoscopic risk stratification and optimizes clinical resource allocation.
Core Tip: This systematic meta-analysis quantifies the associations of non-invasive clinical features and laboratory biomarkers with ulcerative colitis (UC). Based on 389 studies, bloody mucopurulent stools and tenesmus are strongly associated with UC, while perianal fistulae and abdominal masses link more directly to Crohn’s disease. Furthermore, fecal calprotectin, erythrocyte sedimentation rate, and C-reactive protein show significant associations with UC activity and differential risks. Mapping these clinical and biomarker associations offers an evidence-based framework to optimize patient prioritization for invasive endoscopy.
