Changes over time in the clinical characteristics of liver transplant candidates and prognostic factors for transplant accessibility and postoperative outcomes

Background: The selection process for liver transplant (LT) candidates is becoming increasingly complex. This is partly due to the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) among LT candidates and the higher burden of comorbidities related to both metabolic syndrome and aging. However, no validated tools are currently available to identify prognostic factors for selection and accessibility to LT and no comprehensive data exist on the LT pathways, despite the growing need for such instruments. Study Objectives: To identify clinical factors associated with LT candidates outcomes, specifically: 1) access to the waiting list, 2) access to LT, and 3) post-transplant survival. Methods: All patients referred for LT evaluation at the Transplant Center of Policlinico Umberto I from 2011 to 2020 (n=732) were consecutively enrolled. A total of 50 patients were excluded due to the presence of acute-on-chronic liver failure (ACLF) and/or acute liver failure (ALF), and 135 patients were excluded due to a stable lack of LT indication. Statistical analysis was performed using different multivariate statistical models: a) Fine and Gray competing risks multivariate analysis for access to the waiting list and LT, and b) multivariate Cox regression for post-transplant survival. Clinically significant variables considered relevant to each specific outcome were included as covariates in the respective models. Results: The analysis of patients with a stable LT indication (n=547) demonstrated a progressive increase in MASLD etiology among LT candidates (from 35.2% to 44.6%), making it the second leading cause of liver disease. Similarly, alcoholic etiology increased in frequency (from 41.8% to 55.4%), while hepatitis C virus (HCV) etiology showed a marked decline (from 37.7% to 24.6%). Two multivariate Fine and Gray competing risks models were constructed: Model A, incorporating liver disease-related variables, and Model B, incorporating patient comorbidities. Both models identified significant independent factors associated with outcomes. In Model A, independent variables associated with an increased likelihood of being listed for LT included age (SHR 0.981, 95% CI 0.966-0.996, p=0.012), hepatocellular carcinoma (HCC) (SHR 1.967, 95% CI 1.438-2.689, p<0.001), and MASLD (SHR 1.569, 95% CI 1.178-2.086, p=0.002). Model B revealed that among patients listed for LT, male sex was the only variable independently associated with an increased likelihood of undergoing transplantation (SHR 2.253, 95% CI 0.953-6.985, p=0.007). Regarding post-LT mortality, multivariate Cox analysis identified chronic obstructive pulmonary disease (COPD) as the only factor associated with increased mortality risk (HR 3.998, 95% CI 1.395-11.453, p=0.01), while variables related to liver disease etiology, severity, and other comorbidities did not significantly impact post-LT survival. Conclusions: Despite having a higher burden of comorbidities, patients with MASLD are more frequently listed for LT, likely due to a lower tendency for clinical improvement and a higher incidence of HCC. Female sex is disadvantaged in the waiting list, highlighting the need to enhance equity in LT access by refining prioritization scores and allocation strategies. The LT selection process is highly stringent, with COPD emerging as the only factor independently associated with post-LT mortality, likely due to its role as a risk factor for major causes of death, including infections and malignancies.