Prediction Model with Serum RBP4 and Clinical Features for Postoperative Recurrence of Intrahepatic Bile Duct Stones: A Retrospective Cohort Study

Postoperative recurrence of intrahepatic bile duct stones is common and is influenced by biliary stricture, cholangitis, and metabolic inflammation; however, a validated preoperative prediction tool is lacking. A nomogram combining serum retinol-binding protein 4 (RBP4) with clinical and imaging features was constructed and temporally validated to assess individualized recurrence risk. In a single-center retrospective cohort of 571 patients with complete stone clearance (2015-2022), split into development (n = 357) and temporal validation (n = 214) cohorts, the outcome was imaging-confirmed recurrence ≥6 months after surgery. A Cox nomogram with RBP4 modeled using restricted cubic splines, adjusted for age, albumin, eGFR, history of cholangitis, bilobar involvement, biliary stricture, stone diameter, and diabetes, was internally validated using 1,000 bootstrap resamples. Model performance was assessed using the C-index, time-dependent AUC, Brier score, calibration, and decision curve analysis and was compared with that of a clinical-only model. Over 1,695 person-years of follow-up, 184 recurrences occurred (1-year and 3-year recurrence rates: 8.96% and 31.84%, respectively). RBP4 showed an independent nonlinear association with recurrence (P < 0.001) and consistent results in sensitivity analyses. The nomogram provided clear risk stratification (log-rank P < 0.001) and good calibration. AUCs were 0.78 and 0.76 in the development cohort and 0.74 and 0.72 in the validation cohort at 1 and 3 years, respectively; corresponding C-indices were 0.76 and 0.72. Adding RBP4 significantly improved model fit (P < 0.001) and yielded net benefit across threshold probabilities ranging from 10% to 30%. Preoperative RBP4, combined with clinical and imaging features, may facilitate individualized estimation of 1-year and 3-year recurrence risk, with acceptable performance in temporal validation, although external validation remains necessary.