MASH Comorbidities May Drive Worse Transplant Outcomes

Patients with metabolic dysfunction–associated steatohepatitis (MASH) awaiting liver transplant face significantly worse long-term survival than matched individuals without MASH, but that excess risk disappears once kidney dysfunction, diabetes, and obesity are accounted for, according to a national cohort study recently published online in JAMA Surgery.¹

Understanding the Impact of MASH on Transplant Outcomes

Although MASH is among the fastest-growing indications for liver transplant, researchers highlighted that long-term outcomes remain suboptimal. They hypothesized that systemic comorbidities frequently accompanying MASH, like obesity, diabetes, and kidney dysfunction, more significantly impact outcomes than liver disease severity. To test their theory, the researchers compared overall, waiting-list, and post-transplant mortality among patients with vs without MASH.

The study population consisted of 14,861 adults with MASH on the liver transplant waiting list between January 2010 and May 2023, drawn from the Organ Procurement and Transplantation Network (OPTN) database, each of whom was matched 1:1 to a patient without MASH by exact Model for End-Stage Liver Disease (MELD) score, listing year, sex, age, and transplant region. Those with MASH had a mean (SD) age of 58.7 (8.3), with most (51.3%; n = 7620) being men. The number of patients on the waiting list nearly tripled, the researchers noted, from 608 in 2010 to 1625 in 2023.

Despite identical MELD scores at listing (18.0 in both groups), patients with MASH carried a significantly heavier comorbidity load: higher BMI (32.1 vs 27.0; P < .001), more than twice the rate of diabetes (54.8% vs 20.4%; P < .001), higher dialysis rates (4.5% vs 3.5%; P < .001), and lower estimated glomerular filtration rate (eGFR) of 69.8 vs 80.4 mL/min/1.73 m²; P < .001.

By the time patients came off the waiting list, those with MASH showed faster MELD score progression (23.0 vs 22.0; P < .001) than their matched counterparts, which was associated with steeper kidney function decline (eGFR: 59.3 vs 70.8 mL/min/1.73 m² [P < .001]; dialysis: 12.5% vs 10.9% [P < .001]) and coagulopathy. Patients with MASH had a higher likelihood of waiting-list removal due to transplant receipt (64.7% vs. 61.4%; HR, 1.08; 95% CI, 1.05-1.11; P < .001) and death or clinical deterioration (22.4% vs. 21.2%; HR, 1.06; 95% CI, 1.01-1.11; P = .02) alongside a lower likelihood of removal due to improvement (4.2% vs 6.9%; HR, 0.60; 95% CI, 0.55-0.67; P < .001), the researchers explained.

Comorbidities May Explain the Survival Gap

Unadjusted survival was similar between groups at 1 year (82.5%) but diverged over time, with patients with MASH showing lower survival at 3 years (69.9% vs 71.6%), 5 years (61.7% vs 64.5%), and 10 years (45.3% vs 51.5%; P < .001 for the latter 2 comparisons). This excess mortality reflected both higher waiting-list mortality (HR, 1.08; 95% CI, 1.03-1.13) and posttransplant mortality (HR, 1.26; 95% CI, 1.18-1.36), the researchers noted.

After adjusting for transplant status and MELD score progression, MASH remained independently associated with mortality (adjusted HR [AHR], 1.06; 95% CI, 1.02-1.11; P = .01). However, once the model accounted for comorbidities, namely age, sex, race, kidney function, dialysis status, diabetes, BMI, and functional status, the association disappeared (AHR, 1.01; 95% CI, 0.97-1.06). In addition, among patients already on dialysis at listing, where kidney dysfunction was comparable between groups, no survival difference emerged at any time point.

“…patients with MASH entered the liver transplant waiting list with greater comorbidity burden and had more rapid waiting-list MELD score progression due to kidney dysfunction, suggesting a narrow window to receiving transplant with many patients dying before reaching transplant,” the authors concluded.

The pattern echoes that of past studies, in which type 2 diabetes and cardiovascular comorbidity, rather than fibrosis stage alone, have repeatedly emerged as the strongest predictors of mortality and disease progression. One recent real-world analysis found an adjusted mortality risk nearly 80% higher among patients with baseline diabetes.² A separate review of MASH cirrhosis outcomes reported that 10-year transplant-free survival fell from 81% to 38% in patients with diabetes.³

Targeting Comorbidities May Improve MASH Outcomes

The authors acknowledged several limitations of their study, including its retrospective design and the limited granularity of the OPTN registry data.¹ The study was also subject to potential confounding from allocation policy changes and the COVID-19 pandemic, both of which occurred during the study period. Still, the authors used their findings to reiterate that improving outcomes for patients with MASH requires continued access to transplant information and comorbidity-focused care.

“Dedicated posttransplant MASH clinics and semaglutide use, which was recently approved by the [FDA] for MASH treatment, may provide opportunities to address comorbidities and improve long-term outcomes,” the study authors wrote.

References

1. Shivega WG, Montgomery JR, Hack M, et al. Metabolic dysfunction–associated steatohepatitis comorbidity burden and overall, waiting-list, and post–liver transplant mortality. JAMA Surg. Published online August 5, 2026. doi:10.1001/jamasurg.2026.3205
2. Alkhouri N, Noureddin M. Management strategies for metabolic dysfunction-associated steatotic liver disease (MASLD). Am J Manag Care. 2024 Nov;30(9 Suppl):S159-S174. doi:10.37765/ajmc.2024.89635. PMID: 39513734.
3. Review finds poor outcomes, limited predictive tools in MASH cirrhosis. AJMC^®. April 27, 2026. Accessed September 9, 2026. https://www.ajmc.com/view/review-finds-poor-outcomes-limited-predictive-tools-in-mash-cirrhosis