Preoperative CT-derived skeletal muscle phenotypes, postoperative complication burden, and long-term survival after liver transplantation: a 90-day landmark mediation analysis.

BACKGROUND

CT-derived skeletal muscle index (SMI) and skeletal muscle density (SMD) may complement nutritional and functional assessment before liver transplantation, but pathways linking these body-composition phenotypes to long-term outcomes remain unclear. We evaluated whether cumulative 90-day postoperative complication burden was compatible with an intermediate pathway between lower preoperative SMI or SMD and long-term mortality.

METHODS

This single-center retrospective cohort used a postoperative day-90 landmark, restricting the primary analysis to recipients alive and under follow-up at day 90. SMI and SMD were analyzed separately, with the 90-day Comprehensive Complication Index (CCI) as the mediator and all-cause mortality during a prespecified 5-year post-landmark window as the outcome. Linear mediator and Cox outcome models adjusted for hepatocellular carcinoma, Eastern Cooperative Oncology Group performance status, and MELD 3.0. Percentile 95% confidence intervals (CIs) were obtained from 1,000 nonparametric bootstrap resamples.

RESULTS

Of 245 recipients screened, 205 entered the landmark cohort; 56 (27.3%) died during the prespecified 5-year post-landmark analysis window. Median analyzed follow-up was 3.33 years. For a 1-standard deviation decrease, the approximate natural indirect-effect hazard ratios (HRs) through CCI were 1.155 (95% bootstrap CI, 1.033-1.326) for SMI and 1.190 (1.062-1.382) for SMD. Natural direct-effect CIs included 1 for both exposures, whereas the total-effect CI excluded 1 for SMI but not SMD. Indirect-effect estimates were similar after replacing ECOG with age and delaying outcome follow-up to day 120, but were attenuated after CCI dichotomization.

CONCLUSION

Lower preoperative SMI and SMD showed model-based approximate indirect effects through cumulative postoperative complication burden. These CT-derived muscle phenotypes may complement, but should not replace, comprehensive nutritional and functional assessment. The observational design and incompletely verifiable identification assumptions preclude strict causal or interventional interpretation.