The Association Between Metabolic-Associated Fatty Liver Diseases and Risk of Colorectal Polyps, Neoplasia, and Cancer: A Systematic Review and Meta-Analysis of Over 56 Million Individuals Publisher



Af Azimi Amir FARBOD ; A Ghaffarijolfayi AMIR ; V Rezayifar VIDA ; F Ateen FATEMEH ; Hh Fard Hanie HOSSEINI ; Sk Mohammed San KHASRAW ; H Hosseinizadeh HALE ; S Faizabadi SANAM ; A Keshavarzian ALI ; Ma Mansournia Mohammad ALI
Source: Clinics and Research in Hepatology and Gastroenterology Published:2025

Abstract

Background and aims: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) affect over 30 % of the global population. Extrahepatic manifestations, including colorectal malignancies, represent the second leading cause of death in these patients. This study evaluates the association between NAFLD/MAFLD and colorectal polyps, neoplasia, and cancer. Methods: A systematic search was conducted in PubMed, Web of Science, Scopus, and Google Scholar through June 2025. Observational studies reporting odds ratios (ORs) or hazard ratios for colorectal pathologies in NAFLD/MAFLD patients were included. Quality assessment was performed using Joanna Briggs Institute tools. Random-effects meta-analysis calculated pooled effect sizes with subgroup analyses to explore heterogeneity. Results: Forty-eight studies encompassing 56,175,279 participants were analyzed. NAFLD/MAFLD was associated with significantly increased risk of colorectal polyps (OR 1.86, 95 % CI: 1.51–2.30), adenomas (OR 1.81, 95 % CI: 1.62–2.02), CRC (OR 1.37, 95 % CI: 1.30–1.45), overall neoplasia (OR 1.50, 95 % CI: 1.24–1.81), hyperplastic polyps (OR 1.60, 95 % CI: 1.34–1.91), and multiple adenomas (OR 1.49, 95 % CI: 1.16–1.91). Associations were confirmed in both imaging-based and biopsy-proven studies, with adjusted analyses supporting these findings. However, no significant association was found with advanced or large adenomas. Lean patients (BMI <25 kg/m²) showed stronger associations with adenoma risk than those with BMI ≥25 kg/m² (p = 0.027). Sensitivity analyses confirmed the robustness of the results. Conclusion: NAFLD/MAFLD significantly increases colorectal polyp risk, particularly adenomas, hyperplastic polyps, overall neoplasia, and CRC, emphasizing the need for targeted colorectal screening. Future research should focus on prospective studies and mechanistic insights to enhance preventive strategies. © 2025 Elsevier B.V., All rights reserved.