Effect modification of gallbladder wall thickness on the association between fibrosis-4 index and high-risk colorectal adenoma in patients with gallbladder polyps: a retrospective cross-sectional study

Background Gallbladder polyps (GBPs) and colorectal neoplasia frequently coexist against a background of metabolic dysfunction. This study aimed to investigate the association between the Fibrosis-4 (FIB-4) index and high-risk colorectal adenoma (HRA) in patients with GBPs, and to evaluate the effect modification of gallbladder ultrasound characteristics on this association. Methods This retrospective study included 620 patients with GBPs who underwent colonoscopy at Zhengzhou Central Hospital Affiliated to Zhengzhou University between 2022 and 2025. Patients were classified into no adenoma, non-high-risk adenoma (non-HRA), and HRA groups based on colonoscopic pathology. The Mantel-Haenszel linear trend test was used to assess the dose-response relationship between FIB-4 category and adenoma severity. Multivariable logistic regression was fitted with HRA as the outcome, adjusting for demographic and metabolic covariates. Sensitivity analysis was performed using FIB-4 as a continuous variable (per standard deviation increment). Prespecified subgroup analyses and multiplicative interaction models were conducted, with Wald and likelihood ratio tests (LRTs) evaluating the effect modification of gallbladder wall thickness on the FIB-4-HRA association. Results The FIB-4 category showed a dose-response relationship with adenoma severity (trend P = 0.0039). The risk of HRA in the high FIB-4 group was elevated in the unadjusted model (OR 5.83, P < 0.001) but attenuated after adjustment (aOR 2.32, P = 0.129). The overall aOR per 1-standard deviation (SD) increase in FIB-4 was 1.09 (P = 0.41). Subgroup analysis revealed that the association between per-1-SD increase in FIB-4 and HRA was present only among patients with gallbladder wall thickening (≥3 mm) (aOR = 6.38, P = 0.003), with no significant association in those with normal wall thickness (aOR = 0.94, P = 0.75). The multiplicative interaction term between FIB-4 and gallbladder wall thickness was significant (Wald P = 0.008, LRT P = 0.001). Conclusion Subgroup analyses of this study showed that among patients with GBPs and gallbladder wall thickening, elevated FIB-4 was associated with an increased risk of high-risk colorectal adenoma. This association still requires validation in independent external cohorts.