Evolving Trends and Racial Disparities in Alcohol Associated Liver Disease (ALD), Metabolic Dysfunction Associated Steatohepatitis (MASH) and Hepatitis C Viral Infection (HCV) as Etiology of Liver Transplantation: Past, Present, and Future Projections.

Abstract

Background: Liver transplantation remains the definitive treatment for end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC). While hepatitis C virus (HCV) was historically the leading indication for liver transplant, the introduction of direct-acting antivirals (DAAs) has drastically reduced HCV-related ESLD. In contrast, metabolic dysfunction-associated steatohepatitis (MASH) and alcohol-associated liver disease (ALD) have emerged as predominant causes of liver transplantation. This study evaluates racial and ethnic disparities in liver transplantation indications from 2004 to 2023 and projects future trends through to 2040.

Methods: De-identified data from the Standard Transplant Analysis and Research (STAR) files of the United Network for Organ Sharing (UNOS) database were analyzed to assess temporal trends in the proportion of ALD, HCV, and MASH as etiologies of liver transplant indications using Joinpoint regression. The annual percentage change (APC) in the proportion of etiologies of liver transplantation were reported with a significance level at a p-value of 0.5. Future projections were estimated using the Box-Jenkins methodology of Autoregressive Integrated Moving Average (ARIMA) modelling. Trends were stratified by race/ethnicity to evaluate disparities.

Results: The proportion of liver transplantation attributed to ALD has risen significantly across all racial groups, with American Indian/Alaska Native (AIAN) individuals experiencing the steepest increase. By 2040, ALD is projected to account for 80% of liver transplantation in AIAN populations. MASH-related liver transplantation is also increasing, particularly among Hispanic and White individuals, with projections reaching approximately 40% by 2040. In contrast, HCV-related liver transplantation has sharply declined across all racial groups likely due to the impact of DAAs, however, the Black population continues to experience disproportionately higher rates of HCV-related ESLD.

Conclusion: The shifting landscape of liver transplantation etiologies highlights the growing burden of ALD and MASH, emphasizing the need for targeted prevention strategies. Persistent racial disparities in liver transplant access and outcomes underscore systemic healthcare inequities. Addressing these disparities through equitable healthcare policies, early intervention programs, and improved transplant access is crucial to ensuring fair distribution of transplant resources and improved outcomes for all populations.