Waiting list mortality and 5-year transplant survival benefit of patients with MASLD: An Italian liver transplant registry study

Abstract

Background & aims: International consensus has recently introduced a new definition of metabolic dysfunction-associated steatotic liver disease (MASLD). We sought to analyse epidemiological trends, prognostic features, and transplant survival benefits of patients with MASLD and without MASLD waiting for liver transplantation (LT) in Italy.

Methods: Using the Italian Liver Transplant Registry database, we analysed data from adult patients listed for primary LT attributable to end-stage chronic liver disease between January 2012 and December 2022. Independent multivariable waiting lists and post-transplant survival models were developed for patients with and without hepatocellular carcinoma (HCC). A Monte Carlo simulation was used to create 5-year transplant benefit distributions based on the presence of MASLD, HCC, and model for end-stage liver disease (MELD)-sodium values.

Results: A total sample of 1,941 patients with MASLD and 11,201 patients without MASLD was considered. A significant increase in the prevalence of MASLD as an indication for LT was observed from 2012 to 2022, for both cohorts with HCC (from 17.7 to 30%) and without HCC (from 9.5 to 11.8%) cohorts. Projections suggest that, as early as next year, MASLD will overcome HCV as the second most common indication for transplantation after alcoholic liver disease in Italy. According to univariate and multivariate analyses, MASLD was not an independent predictive factor for patient survival after transplantation. However, it increased the risk of death for patients on the waiting list without HCC (hazard ratio 1.62, p <0.001). At the same MELD-sodium, the 5-year transplant benefit was higher in patients with non-HCC MASLD, followed by patients with HCC, whereas it was lower in patients without HCC and without MASLD.

Conclusions: Patients with non-HCC MASLD had an increased waitlist mortality and 5-year transplant survival benefit compared with other candidates.

Impact and implications: The present research addresses the critical need to understand the evolving landscape of liver transplantation indications, mainly focusing on metabolic dysfunction-associated steatotic liver disease (MASLD) in Italy. Given the significant rise in MASLD cases, these findings highlight that patients with non-HCC MASLD face increased waitlist mortality and benefit more from liver transplantation within 5 years compared with other candidates. The significance of these results lies in their emphasis on the necessity of focusing on patients with MASLD on waiting lists to improve outcomes. By tailoring transplant eligibility criteria and resource allocation, the study provides actionable insights to improve patient survival and optimise liver transplantation practices.

Keywords: MASLD; Transplant Survival Benefit; Waiting list; liver transplantation.

Graphical abstract

Fig. 1

Flow chart of case selection from the SIT database. ALD, alcohol-related liver disease; CE-MASLD, combined aetiology MASLD; LT, Liver transplantation; MASLD, metabolic dysfunction-associated steatotic liver disease; NON-MET, non-metabolic aetiologies; SIT, Informative Transplant System.

Fig. 2

Epidemiological trends and future trajectories of waiting list inscriptions for liver transplantation in Italy according to main aetiologies of liver disease, period 2012–2030. (A) Whole population, (B) patients without HCC, and (C) patients with HCC. Epidemiological trends were graphically represented, and the statistical significance of differences was evaluated using a linear regression model and analysis of variance. Linear regression models were also used to explore future trajectories of patients with MASLD and without MASLD. HCC, hepatocellular carcinoma; MASLD, metabolic dysfunction-associated steatotic liver disease.

Fig. 3

Epidemiological trends and future trajectories of waiting list inscriptions for liver transplantation in Italy according to metabolic-related liver disease categories, period 2012–2030. (A) Whole population, (B) patients without HCC patients, and (C) patients with HCC. Epidemiological trends were graphically represented, and the statistical significance of differences was evaluated using a linear regression model and ANOVA. Linear regression models were also used to explore future trajectories of patients with MASLD and without MASLD. CE-MASLD, combined aetiology MASLD; HCC, hepatocellular carcinoma; MASLD, metabolic dysfunction-associated steatotic liver disease; NON-MET, non-metabolic aetiologies.

Fig. 4

Waiting list competing risk of death/dropout. (A) Whole population, (B) patients without HCC, and (C) patients with HCC. The competing risk method of Fine and Gray used LT and death/dropout as competing events. The competing risk curves were constructed using estimates adjusted (by a multivariable model) for age, sex, blood group, study period, centre volume, and MELD-sodium. CE-MASLD, combined aetiology MASLD; HCC, hepatocellular carcinoma; LT, liver transplantation; MASLD, metabolic dysfunction-associated steatotic liver disease; MELD, model for end-stage liver disease; NON-MET, non-metabolic aetiologies.

Fig. 5

Post-LT survival Kaplan Meier curves. (A) Whole population, (B) patients without HCC, and (C) patients with HCC. Kaplan–Meier curves were compared using the log-rank test. CE-MASLD, combined aetiology MASLD; HCC, hepatocellular carcinoma; LT, liver transplantation; MASLD, metabolic dysfunction-associated steatotic liver disease; NON-MET, non-metabolic aetiologies.

Fig. 6

Five-year transplant benefit (gain in life expectancy months) in patients with HCC, non-HCC MASLD, and non-HCC non-MASLD based on MELD-sodium values. A multistate model converted monthly death probabilities (derived from WL and post-LT survival models) into life expectancy values. The survival benefit of LT (gain in life expectancy) at 60 months was calculated by subtracting the no-LT life expectancy predictions from the post-LT life expectancy predictions. Using the Monte Carlo simulation, we obtained a list of 10,000 outcomes (5-year survival benefit expressed as life expectancy in months) for each population (HCC and non-HCC) based on covariate distributions. This analysis allowed us to describe the correlation between 5-year transplant survival benefit and main study covariates (i.e. MASLD vs. non-MAFLD aetiology, the presence of HCC, and MELD-sodium values). HCC, hepatocellular carcinoma; LT, liver transplantation; MASLD, metabolic dysfunction-associated steatotic liver disease; MELD, model for end-stage liver disease; WL, waiting list.