The Liver Frailty Index improves mortality risk prediction for GEMA-Na

The sodium-corrected Gender-Equity Model for Liver Allocation (GEMA-Na) was developed to mitigate gender disparities in liver allocation, which arise in part from lower muscle mass in women compared with men. Frailty, a measure of muscle health more prevalent in women than in men, is a strong predictor of waitlist mortality (WLM) and can be feasibly assessed in cirrhosis patients using the Liver Frailty Index (LFI). We sought to determine whether LFI could improve WLM risk prediction beyond GEMA-Na. Ambulatory adults with cirrhosis awaiting liver transplant (LT) from the Functional Assessment in Liver Transplantation (FrAILT) study were included. The primary outcome was WLM (death or delisting due to being too sick). Performance of GEMA-Na versus GEMA-Na+LFI Cox proportional hazard models was assessed using Uno's concordance statistic, continuous net reclassification index (NRI), and integrated discrimination improvement (IDI) at 3, 6, and 12 months and in women. Among 1435 patients, 42% were women. Median (IQR) GEMA-Na was 19 (16-23), MELD-Na was 19 (16-23), MELD 3.0 was 19 (16-23), and LFI was 3.9 (3.4-4.3). Median follow-up was 11 months (5-25). WLM was 3.5%, 7.3%, and 13.0% at 3, 6, and 12 months. Performance characteristics demonstrate improved model prediction with GEMA-Na+LFI versus GEMA-Na. Incorporating LFI into GEMA-Na enhanced WLM prediction, including among women, a population historically disadvantaged in liver allocation. While GEMA-Na reduces gender disparities related to renal dysfunction, the added prognostic value of frailty highlights muscle health as an independent and actionable determinant of outcomes. These findings support routine frailty assessment to better stratify risk and to potentially guide timely interventions such as prehabilitation or expedited LT.