External validation of the SNAPP score for hepatocellular carcinoma recurrence after living donor liver transplantation.

BACKGROUND

Binary morphologic criteria cannot capture biologic heterogeneity among living donor liver transplantation (LDLT) recipients. SNAPP score (tumor size, number, AFP, PIVKA-II, PET/CT) yields a graded recurrence-risk estimate but lacks independent validation. We externally validated SNAPP for hepatocellular carcinoma (HCC) recurrence after LDLT.

METHODS

SNAPP was applied without refitting in 230 LDLT recipients with HCC at two Korean centers and benchmarked against Milan, French-AFP, Metroticket 2.0, MoRAL, RETREAT, and three LDLT-derived selection systems (Kyoto, Medanta LDLT, and National Cancer Center Korea). Discrimination, calibration, Brier score, and reclassification were assessed using IPCW-weighted methods with bootstrap 95% CIs.

RESULTS

Among 230 patients (median follow-up, 91.5 mo), 49 (21.3%) recurred. SNAPP achieved discrimination comparable to the best pretransplant tool, MoRAL (Harrell C-index, 0.756; 95% CI, 0.690-0.821), and exceeded Milan (0.503; Holm-adjusted p=0.01). Discrimination was numerically higher than Metroticket 2.0 (0.605) and three LDLT-derived systems (C-index difference, 0.10-0.15), but none of these differences survived correction for multiplicity (Holm-adjusted p=0.24). RETREAT, a posttransplant benchmark, reached 0.807. Calibration-in-the-large was -0.068; slope, 0.59 (95% CI, 0.43-0.77). Within Milan-eligible patients (n=217), SNAPP resolved a monotonic, approximately 5.9-fold gradient in 5-year cumulative recurrence (11.9%, 48.8%, 70.0%). Reclassification favored SNAPP over Milan, French-AFP, and Metroticket 2.0; the center-adjusted hazard ratio per point 1.79 (95% CI, 1.51-2.14).

CONCLUSIONS

SNAPP showed discrimination comparable to MoRAL and exceeded Milan, with numerically higher but not definitively superior discrimination compared with Metroticket 2.0, French-AFP, and three LDLT-specific selection systems, while resolving biologic heterogeneity within Milan-eligible candidates using only pretransplant variables. With near-zero calibration-in-the-large but a slope below unity, SNAPP supports risk stratification at listing, though individualized probability estimates require recalibration.