DAY 2 - Impact of Sex on Liver Transplant Waitlist and Post-Transplant Outcome by Disease Etiology

Liver transplantation is a critical intervention for end-stage liver disease, but access to this life-saving procedure is affected by factors such as sex and disease etiology. Due to higher waitlist mortality (WLM) observed among females, the Model for End-stage Liver Disease (MELD) 3.0 was introduced in July 2023 to improve liver allocation. However, a significant knowledge gap remains regarding how liver disease etiology influences sex-based waitlist outcomes.

At the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Dr. Chencheng Xie, Assistant Professor of Internal Medicine at the University of South Dakota, presented findings on how sex and disease etiology impact liver transplant waitlist and post-transplant outcomes.

Dr. Xie’s team analyzed data from the United Network for Organ Sharing (UNOS) database covering 2014 to 2022. The study included 88,601 adult liver transplantation listings, with 35.5% females. Listings were categorized by disease etiology as follows: 36.1% for alcohol-associated liver disease (ALD), 24.3% for metabolic-associated steatohepatitis (MASH), 23.9% for hepatitis C virus (HCV), 2.4% for hepatitis B virus (HBV), 8.6% for chronic cholestatic liver disease (CCLD), 1.6% for metabolic liver disease, and 3.2% for fulminant hepatic failure (FHF). Cumulative waitlist mortality was analyzed by competing for liver transplantation (LT), and a Fine-Gray multivariable regression model was used to examine factors influencing waitlist outcomes.

The study found significant sex-based differences in waitlist mortality. Females on the waitlist were generally younger, shorter, and had lower mean glomerular filtration rates (GFR). Females had higher mean MELD scores, indicating more severe liver disease and a greater need for transplantation. Additionally, females were more likely to be Black. They tended to have a better functional status, as indicated by a Karnofsky Performance Status Score (KPSS) above 40%.

The findings revealed that females had higher 90-day waitlist mortality for MASH and CCLD, while they had lower 90-day mortality for ALD. “In the alcohol liver disorder, you see the opposite result,” said Dr. Xie. As ALD is the most common liver disease etiology, confirming these trends through large prospective studies is essential, particularly when considering liver disease type (ALD vs. non-ALD) in liver allocation policies. No significant differences in 90-day waitlist mortality were observed between sexes for HCV, HBV, metabolic liver disease, FHF, or hepatocellular carcinoma. These results suggest that sex-based differences in waitlist mortality by disease etiology could inform policies for optimal liver allocation.

Dr. Xie concluded that understanding these differences can help clinicians manage patients on the liver transplantation waitlist and make prioritization decisions. He emphasized the need for further studies to confirm these findings, especially given the prominence of ALD as a leading liver disease etiology.

This research raises broader questions: How can liver allocation policies be adjusted to account for these sex-based differences in waitlist mortality by etiology? What biological or socioeconomic factors underlie these differences? And how might these findings impact post-transplant outcomes?