Prevalence and Associated Factors of Nonalcoholic Fatty Liver Disease in Patients with Inflammatory Bowel Disease: An Updated Global Systematic Review and Meta-Analysis of over 1.5 Million Individuals

Abstract

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver condition worldwide, with its burden increasingly recognized among individuals with inflammatory bowel disease (IBD). The complex interplay between chronic intestinal inflammation, metabolic dysregulation, and hepatic pathology has heightened concern about the susceptibility of IBD patients to NAFLD. This study aims to systematically evaluate the global prevalence of NAFLD among patients with IBD and to identify key demographic, geographic, clinical, and pharmacologic factors associated with its development. METHODS: A comprehensive search of four electronic databases-PubMed, Embase, Scopus, and Web of Science-was conducted up to January 21, 2025. Eligible studies included observational research reporting the prevalence of NAFLD in patients with IBD. Random-effects meta-analysis was used to estimate the pooled prevalence of NAFLD. In addition, subgroup analyses and meta-regression were conducted to investigate potential sources of heterogeneity and identify associated demographic, clinical, and geographic factors. RESULTS: A total of 64 studies comprising 1 532 811 individuals were included. The pooled global prevalence of NAFLD in IBD patients was 25.4 (95 CI: 23.1-27.8). Prevalence was higher in adults (26.0, 95 CI: 24.0-29.0) than in pediatric patients (7.0, 95 CI: 1.0-16.0). Among males and females, prevalence was 32.1 (95 CI: 29.3-36.0) and 22.9 (95 CI: 20.2-25.7), respectively. Among IBD subtypes, the prevalence was 21.4 in ulcerative colitis (UC; 95 CI: 15.2-28.3) and 22.8 in Crohn's disease (CD; 95 CI: 20.0-25.0). Geographic variation was substantial, ranging from 16.0 in Asia (95 CI: 10.0-25.0) to 32.0 in Europe (95 CI: 27.0-38.0) and Africa (95 CI: 10.0-57.0). NAFLD prevalence was also influenced by diagnostic method, with higher rates using transient elastography (38.0, 95 CI: 27.0-49.0) and liver biopsy (37.0, 95 CI: 17.0-59.0). By disease location, the highest NAFLD prevalence in CD was in patients with upper GI involvement (67.0, 95 CI: 1-99.0), while the lowest was in ileo-colonic disease (21.0, 95 CI: 12.0-32.0). For UC, prevalence ranged from 27.0 (95 CI: 17.0-39.0) in left-sided colitis to 18.0 (95 CI: 8.0-29.0) in proctosigmoiditis. No significant association with NAFLD was observed for any IBD medication analyzed, including 5-aminosalicylic acid (5-ASA; OR: 0.85, 95 CI: 0.69-1.05; P = .15), azathioprine (OR: 1.04, 95 CI: 0.78-1.40; P = .76), vedolizumab (OR: 0.81, 95 CI: 0.45-1.44; P = .48), Ustekinumab (OR: 1.03, 95 CI: 0.58-1.82; P = .90), anti-TNF agents (OR: 1.20, 95 CI: 0.85-1.68; P = .28), and systemic corticosteroids (OR: 1.43, 95 CI: 0.89-2.32; P = .13). CONCLUSION: NAFLD is a common comorbidity among patients with IBD, affecting over one in four individuals, with higher prevalence observed in adults, males, and certain geographic regions. Variation by diagnostic modality and disease location was also noted; however, these subgroup findings are based on limited data and should be interpreted with caution. Overall, the results highlight the importance of incorporating liver health screening into routine IBD management, particularly for high-risk populations, and underscore the need for future prospective studies to refine risk stratification and management strategies. The study systematically evaluates the global prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) in patients with Inflammatory Bowel Disease (IBD), identifying key demographic, geographic, clinical, and pharmacologic factors associated with its development, with findings highlighting significant variability across regions and subgroups.