Association between metabolic dysfunction-associated steatotic liver disease and risk of early-onset advanced colorectal neoplasia: a systematic review and meta-analysis.

Abstract

Background: With the rising global incidence of early-onset colorectal cancer (EOCRC) and its aggressive clinical behavior, we conducted a systematic review and meta-analysis to synthesize evidence from cohort studies and quantify the association between metabolic dysfunction-associated steatotic liver disease (MASLD), including its prior definitions (non-alcoholic fatty liver disease/metabolic associated fatty liver disease), and early-onset advanced colorectal neoplasia (eoACRN), providing evidence for risk stratification and early intervention.

Methods: A systematic search of PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) was conducted up to March 20, 2026, including English and Chinese studies. Observational cohort and cross-sectional studies evaluating MASLD-related hepatic steatosis and eoACRN were included. Adjusted odds ratios (ORs) were pooled using random-effects models. Subgroup and sensitivity analyses assessed heterogeneity and robustness. Publication bias was evaluated using Egger's test and funnel plots.

Results: Ten observational studies (n=76,688) showed that MASLD-related hepatic steatosis was associated with increased risk of early-onset advanced colorectal adenoma (OR =2.03) and EOCRC (OR =1.29). In sensitivity analyses excluding cross-sectional studies, the association with EOCRC remained significant [OR =1.28, 95% confidence interval (CI): 1.20-1.37]. Subgroup analyses suggested a higher effect in males (OR =3.93), based on three studies. In the diabetes subgroup, the association was not significant (OR =2.16), but became significant after excluding one study (OR =2.93, 95% CI: 1.34-6.43). BMI-stratified analyses did not identify overweight/obesity-defined MASLD as a distinct high-risk phenotype; however, sensitivity analyses combining studies using different BMI cut-offs showed a significant association (OR =2.67).

Conclusions: In Asian populations, MASLD-related hepatic steatosis is associated with increased eoACRN risk. However, substantial heterogeneity, limited subgroup evidence, and low certainty warrant cautious interpretation. Further prospective studies are needed to clarify mechanisms, and to improve personalized screening strategies for high-risk young populations.