The Liver Transplant Comorbidity Index (LTCI) : A composite index of ambulatory Pre-LT factors to identify patients at increased risk of Post-LT Mortality

Background: Frailty is strongly associated with mortality after liver transplantation. However, national guidelines discourage its use as a sole reason to decline a patient for liver transplantation, as some frail patients have acceptable outcomes. We aimed to develop a composite index, the Liver Transplant Comorbidity Index (LTCI), integrating frailty and other comorbidities, as a risk factor for longer-term (3-year) post-transplant mortality. Methods: This 8-center prospective Functional Assessment in Liver Transplantation (FrAILT) Study included adult recipients of a primary deceased donor liver transplant from 2012-2022. Frailty was measured using the Liver Frailty Index (LFI ≥4.5=frail). Other candidate variables included demographics, laboratories, and comorbidities. Cox proportional hazards regression with best subset selection was used to identify risk factors of 3-year post-transplant death. The final model was selected based on Aikaike Information Criterion and clinical pragmatism. Results: Of 1,472 liver transplant recipients. 290 (20%) were frail. Three-year post-transplant mortality was higher in frail versus non-frail patients (13 vs. 8%; p =0.03). The final LTCI included 5 variables: frailty, coronary artery disease, hepatocellular carcinoma, renal dysfunction, and diabetes. Three-year post-transplant mortality in low-, moderate-, and high-risk LTCI groups was 93%, 87%, and 80% respectively. In multivariable analysis, after adjusting for donor factors (age, DCD), both moderate- (HR 2.23; 95% CI 1.46-3.40; p <0.001) and high-risk (HR 2.78; 95% CI 1.67-4.64; p <0.001) status were associated with 3-year post-transplant mortality. Conclusion: The LTCI, comprising 5 pre-transplant clinical parameters, effectively identifies patients at increased risk of post-transplant mortality. By integrating frailty in the context of other co-morbidities, the LTCI can help providers better weigh the relative transplant risks and benefits and standardize selection of transplant candidates.