Liver donor macrosteatosis is associated with adverse long-term outcomes exclusively in metabolic dysfunction-associated steatotic liver disease recipients: a U.S. transplant registry analysis over the last decade

Introduction

Metabolic dysfunction-associated steatotic liver disease [MASLD, formerly known as non-alcoholic fatty liver disease (NAFLD)] and alcohol-associated liver disease (ALD) are the leading causes of chronic liver disease in the United States (U.S.) (1,2). MASLD is tightly linked to the epidemic of metabolic syndrome, which affects over 40% of U.S. adults (3,4). In western countries, MASLD is estimated to affect more than 30% of the adult population (3). The growing rates of obesity and metabolic syndrome become particularly relevant in the context of alcohol use, with more than 90% of patients with chronic heavy alcohol use developing hepatic steatosis independent of metabolic health (5,6). With these two drivers of steatotic liver disease (SLD) rising in the general population, a substantial proportion of deceased organ donors are expected to harbor moderate-severe steatosis.

Macrovesicular steatosis is defined histologically by the presence of large fat droplets within hepatocytes and quantified using the percentage of liver parenchyma containing fat on biopsy (7,8). In the context of liver transplantation (LT), donor livers with moderate-severe macrovesicular steatosis (Mas30), defined as >30% steatosis, are considered high-risk grafts due to data suggesting an increased risk of early allograft failure and lower graft survival (GS) in the first year post-LT (9). Historically, these concerns have led to a high rate of organ decline by transplant centers, with one recent analysis showing that >50% of Mas30 grafts are discarded (10).

Over the last decade, the use of SLD grafts has increased, with studies showing long-term GS comparable to grafts without steatosis (11-13). Machine perfusion (MP) has further optimized 90-day GS, driving a nearly sevenfold rise in the use of Mas30 grafts (odds ratio 7.89; P<0.001) (14-16). Nevertheless, the long-term effects of donor macrovesicular steatosis in recipients with SLD remain incompletely defined, especially beyond the first postoperative year. Existing evidence is largely derived from historic cohorts, likely underrepresenting current organ-allocation practices, and contemporary analyses considering metabolic dysfunction and alcohol-related liver disease (MetALD) have not been described (10,17).

As the prevalence of cardiometabolic risk factors rises in both donors and recipients, clarifying these relationships is increasingly important. Therefore, we aimed to address this gap in the literature by describing the prevalence of Mas30 grafts in recipients with SLD and evaluating the association of Mas30 grafts with early, intermediate, and long-term post-LT GS. We hypothesized that Mas30 grafts would be associated with worse long-term recipient outcomes, particularly among patients with MASLD, who are already predisposed to lipotoxicity, insulin resistance, and increased susceptibility to perioperative injury, thereby amplifying the adverse impact of graft with steatosis. We present this article in accordance with the STROBE reporting checklist (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2026-0143/rc).

Methods

Study population

We performed a retrospective cohort study using the United Network for Organ Sharing (UNOS) national registry, which captures all organ donors, wait-listed LT candidates, and LT recipients in the U.S. through the Organ Procurement and Transplantation Network (OPTN). We identified recipients from January 1, 2014, through April 5, 2024. We excluded recipients with any of the following: (I) missing donor macrovesicular steatosis data; (II) pediatric candidates (<18 years); (III) recipient status 1A at LT time; (IV) multiple-organ transplants; (V) living-donor liver transplants; and (VI) extreme malnutrition [body mass index (BMI) <18.5 kg/m²] (Figure 1).

Figure 1 Algorithm for patient selection and cohort distribution. Patients without donor macrosteatosis data, transplanted before 2014, pediatric recipients, status 1A recipients, multiple-organ transplants, those with extreme malnutrition, and living-donor recipients were excluded. The final cohort included 27,164 LT recipients (14,270 SLD and 12,894 non-SLD). The SLD cohort was further stratified by SLD etiology and donor macrovesicular steatosis severity. ALD, alcohol-related liver disease; BMI, body mass index; LT, liver transplant; Mas30, moderate to severe macrovesicular steatosis (>30%); MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic and alcohol-related liver disease; Mild-MaS, mild macrovesicular steatosis (5% to 30%); None-MaS, no macrovesicular steatosis (<5%); SLD, steatotic liver disease; Status 1A, UNOS designation for acute liver failure requiring urgent transplant.

The Cleveland Clinic Foundation and the Virginia Commonwealth University deemed the UNOS database as publicly available de-identified data; thus, institutional review board (IRB) approval was not required, and individual informed consent was waived. The data reported here were supplied by UNOS as the contractor for OPTN. The interpretation and reporting of these data are the sole responsibility of the authors and do not represent an official interpretation of OPTN or the US government. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Group definition

Donor liver macrovesicular steatosis, abstracted from procurement biopsy reports in UNOS, was grouped as none (<5% macrosteatosis), mild (5–30% macrosteatosis), and Mas30 (>30% macrosteatosis) (Figure 1). Donors with Mas30 were considered high-risk macrosteatotic liver donors, following the threshold supported by the literature (16,18,19). Recipients with SLD were composed of three subtypes: MASLD, MetALD, and ALD. MASLD was identified using UNOS diagnostic codes 4208 and 4213 (cryptogenic cirrhosis plus obesity) and 4214 (fatty liver/non-alcoholic steatohepatitis) (3,17). The UNOS database does not include a designated MetALD diagnosis; therefore, based on proposed criteria and published studies (17), we defined MetALD as: (I) a primary diagnosis of MASLD with a secondary diagnosis of ALD (or vice versa) or (II) a primary diagnosis of ALD with diabetes and/or obesity (BMI thresholds below), adjusted for ascites severity. ALD was defined using codes 4215 (alcoholic cirrhosis), 4217 (acute alcoholic hepatitis), and 4219 (acute alcohol-associated hepatitis with or without cirrhosis).

Obesity was defined as BMI ≥30 kg/m² for non-Asian recipients and ≥27.5 kg/m² for Asian recipients (20). To account for fluid overload, we subtracted 5% of body weight for mild ascites and 10% for moderate ascites per expert consensus (17).

Primary outcome

The primary outcome of the study was GS, defined by OPTN/Scientific Registry of Transplant Recipients (SRTR) as survival without retransplantation or death from any cause (21). The outcome was evaluated at 3 time points: within 90 days (early GS) within 1 year (intermediate-term GS) and within 3 years (long-term GS).

Statistical analysis

Categorical variables were summarized as counts (%) and compared across donor macrovesicular steatosis strata using Chi-square tests. Continuous variables were reported as medians (Quartile 1–Quartile 3) and compared using Kruskal-Wallis tests due to the non-normal distribution of the data. Body surface area (BSA) was calculated using the Du Bois formula: BSA (m²) = 0.007184 × [weight (kg)]^0.425 × [height (cm)]^0.725.

Survival functions were estimated with Kaplan-Meier methods and compared with log-rank tests overall, by recipient phenotype (SLD), by steatosis strata (<5%, 5–30%, >30%), and within SLD subtypes (MASLD, MetALD, ALD). GS was assessed across three clinically relevant time periods: early (90-day), intermediate (1-year), and long-term (3-year) post-transplant.

Temporal trends in donor macrosteatosis use were evaluated with Cochran-Armitage trend tests (categorical proportions by calendar year). Regional differences were compared using χ² tests across UNOS regions. Analyses used complete cases after prespecified exclusions; missingness in included covariates was minimal and not imputed.

To identify prognostic factors, Cox proportional hazards models were constructed using an interaction term between donor macrovesicular steatosis and SLD subtype [MASLD (reference), MetALD, ALD] to assess whether the effect of donor steatosis on GS differed across SLD subtypes. Models were adjusted for donor risk index (continuous), recipient age ≥60 years, recipient diabetes mellitus, recipient race/ethnicity [non-Hispanic White (reference), Black, Hispanic, Asian, other], and recipient obesity (BMI ≥30 kg/m²). MP was identified using the designated binary variable in the UNOS database indicating whether MP was used for graft preservation, without differentiating between specific perfusion modalities. The DRI is a validated score that includes a large number of donor variables, such as donor age, cause of death, race/ethnicity, donation after circulatory death (DCD) status, graft type, donor height, cold ischemic time, and organ sharing status (22). Separate models were fit for each time period (90-day, 1-year, and 3-year). The Breslow method was used for handling tied event times. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) are reported. All analyses were two-sided with α=0.05 and performed in Stata (v19; StataCorp) and R (v4.3).

Sensitivity analyses

Several sensitivity analyses were performed to evaluate the robustness of our findings in MASLD recipients receiving a Mas30 graft. Donor-related sensitivity analyses included: excluding donors with cardiometabolic risk factors (defined as donor history of diabetes mellitus, hypertension, or BMI ≥30 kg/m²), excluding extended criteria donors (defined according to UNOS criteria), and restricting to DCD donors. Recipient-related sensitivity analyses included: restricting to recipients younger than 50 years, excluding recipients with Model for End-Stage Liver Disease (MELD) score >30, excluding recipients with hepatocellular carcinoma, and censoring recipient cardiovascular deaths, as these are important factors that can confound our analyses. Finally, we conducted competing risk analyses using Fine-Gray subdistribution hazard models. Two competing risk models were constructed, one treating non-graft deaths as a competing event, as they often reflect pre-existing recipient comorbidities rather than graft dysfunction itself (23). Another focusing only on cardiovascular deaths as the competing event, given the higher cardiovascular mortality associated with MASLD recipients.

Results

Donor and recipient characteristics

A total of 27,164 recipients were included in the study (14,270 SLD, and 12,894 non-SLD). In the group of recipients with SLD, about one-third of transplanted liver grafts had mild macrovesicular steatosis (33.5%) and only 4.7% had Mas30. Donor age differed between categories of donor macrovesicular steatosis (median Mas30: 45 years, mild: 51 years, none: 50 years; P<0.001). Donors with Mas30 had the highest amount of Hispanic patients (Mas30: 22.1%, mild: 16.7%, none: 12.3%; P<0.001) and patients with heavy alcohol use (23.7%, 23.2%, 20.2%, respectively; P<0.001). BSA was higher in donors with Mas30 compared to those with mild and no degree of macrovesicular steatosis (median 2.06, 2.04, 1.96 m², respectively; P<0.001). BMI was likewise higher in donors with Mas30 compared to other macrovesicular steatosis categories (median 32.18, 31.25, 28.27 kg/m², respectively; P<0.001). Type 2 diabetes was most frequent in donors within the mild category compared to those with no degree of macrovesicular steatosis and Mas30 (17.5%, 21.2%, 19.5%, respectively; P=0.02). Donor sex distribution was similar across categories (male 55.9%, 58.1%, 57.0%, respectively; P=0.34).

On the recipient side, patients who received Mas30 grafts were more likely to be older (median Mas30: 58 years, mild: 57 years, none: 57 years; P=0.03) and male (74.5%, 70.5%, 65.7%, respectively; P<0.001). MELD at LT was lower in Mas30 grafts (median 20.0, 23.0, 24.0, respectively; P<0.001). Recipient age distribution and most clinical comorbidities were largely similar across groups. Tables 1,2 summarize donor and recipient characteristics across macrovesicular steatosis strata.

Prevalence of liver transplants by donor steatosis group

Use of macrovesicular steatotic liver grafts declined over the study. In 2014, liver steatosis (5–30% or >30% macrovesicular steatosis) was observed in approximately 37% of all grafts, compared with about 30% in 2024. This pattern was less pronounced for recipients with SLD (37.4% in 2014 vs. 36.8% in 2024) than for those without SLD (37.2% in 2014 vs. 29.7% in 2024). Looking over time, the decline in Mas30 grafts occurred after a peak in 2018–2019 at 6–6.5% (SLD P=0.001; non-SLD P<0.001). Mild macrovesicular steatosis donor utilization fell modestly over the last decade (SLD P=0.02; non-SLD P=0.02). In recipients with and without SLD, the proportion of no macrovesicular steatosis rose significantly over 2014–2024 (P<0.001), reaching over 63% in 2024. Prevalence over time in the use of steatotic and non-steatotic donors can be found in Figure 2. Machine perfusion utilization among SLD recipients is depicted in Table S1.

Figure 2 Temporal trends in liver donor utilization categorized by degrees of macrovesicular steatosis. Between 2014 and 2024, liver donors with >30% macrovesicular steatosis sharply declined in utilization, whereas utilization of non-steatotic liver donors climbed as high as 66% in both SLD and non-SLD recipients. LT, liver transplant; SLD, steatotic liver disease.

Geographical variation in moderate-severe macrovesicular donor organ use

In regard to geographical distribution (Figure S1), utilization of Mas30 grafts was concentrated in the southern UNOS regions (Regions 3, 4, 5, and 11) and Region 10. Among recipients with SLD, Region 10 had the highest use of Mas30 grafts with a total of 7.2% while Region 6 had the lowest with a total of 1.86%. In general, the prevalence of Mas30 grafts was higher in the midwest (5.8%) and southern regions (5.2%), followed by the northeast (4.9%), and finally the west (3.3%).

Comparing the impact of macrovesicular liver donors

Considering all included patients, overall early post-LT GS was 94.9% and long-term GS was 87.2%. Early post-LT GS was significantly lower for recipients of Mas30 grafts (92.4% Mas30, 94.3% mild, 95.4% none; log-rank P<0.001), but long-term GS was similar across groups (87.5%, 86.7%, 86.8%, respectively; log-rank P=0.06). Among recipients with SLD, receiving a Mas30 graft was associated with reduced early post-LT GS (91.5% Mas30 vs. 95.1% mild vs. 95.5% none; log-rank P<0.001, Figure S2A) but was not associated with a difference in long-term GS (87.9%, 88.0%, 87.9%, respectively; log-rank P=0.20, Figure 3A).

Figure 3 Long-term graft survival by donor macrosteatosis and steatotic liver disease etiology. Kaplan-Meier survival curves depicting long-term (3-years) graft survival following liver transplantation stratified by degree of donor macrovesicular steatosis [<5% (short dashes; blue navy), 5–30% (long dashes; red), and >30% (solid line; dark green)]. (A) All recipients with SLD. (B) Recipients with MASLD. (C) Recipients with MetALD. (D) Recipients with ALD. Numbers at risk are displayed below each panel. Log-rank P values are depicted in the lower left corner of each graph. Numbers in parentheses represent the number of graft loss events occurring since the prior time point. ALD, alcohol-related liver disease; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic and alcohol-related liver disease; SLD, steatotic liver disease.

Comparing the impact of macrovesicular liver donors among SLD subtypes

When stratified by SLD subtype, the influence of donor macrovesicular steatosis differed markedly across recipients with MASLD, MetALD, and ALD. Among recipients with MASLD, donor macrovesicular steatosis strata had the strongest association with worsening of GS. In the early post-LT period, GS was lower in recipients of Mas30 grafts (87.8%, 93.6%, and 95.3% for Mas30, mild, and no macrosteatosis, respectively; log-rank P<0.001, Figure S2B). These differences persisted into long-term follow-up with GS of 83.0%, 86.6%, and 87.5%, respectively (log-rank P=0.01, Figure 3B).

Within recipients with MetALD, Mas30 grafts were not associated with differences in early post-LT GS (93.5%, 94.8%, and 95.3%, respectively; log-rank P=0.52, Figure S2C) or long-term GS (88.9%, 87.2%, and 86.4%, respectively; log-rank P=0.88, Figure 3C). In recipients with ALD, Mas30 grafts were similarly not associated with differences in early post-LT GS (94.8%, 96.9%, and 96.0%, respectively; log-rank P=0.17, Figure S2D) or long-term GS (90.6%, 90.3%, and 89.5%, respectively; log-rank P=0.77, Figure 3D). Intermediate GS was also analyzed and was not associated with significant differences across groups (Figure S3).

Among non-SLD etiologies, Mas30 grafts were not associated with differences in long-term GS in recipients with viral hepatitis, autoimmune liver disease, or other etiologies (log-rank P=0.06, P=0.95, and P=0.31, respectively; Figure S4).

Prognostic factors affecting post-liver transplant survival across SLD subtypes

Among recipients with MASLD, receiving a Mas30 graft was the strongest independent detrimental predictor of GS across all time periods (Table 3; Figure S5). During the early post-LT period, Mas30 grafts were associated with a nearly threefold increase in the hazard of GS compared with non-steatotic grafts (aHR 2.93, P<0.001). Notably, mild macrovesicular steatosis also conferred a significantly elevated early risk (aHR 1.38, P=0.01). The hazards of Mas30 grafts persisted at intermediate (aHR 2.18, P<0.001) and long-term follow-up (aHR 1.66, P=0.002). Additional factors associated with worse GS included DRI (early: aHR 1.11, P=0.04; intermediate: aHR 1.16, P<0.001; long-term: aHR 1.15, P<0.001), recipient age ≥60 years (intermediate: aHR 1.36, P<0.001; long-term: aHR 1.37, P<0.001) and diabetes mellitus (long-term: aHR 1.16, P=0.04), and recipient obesity (early: aHR 1.24, P=0.04). MP was not significantly associated with GS at any time point (early: aHR 1.33, P=0.22; intermediate: aHR 1.30, P=0.21; long-term: aHR 1.25, P=0.26). Within recipients with MetALD or ALD, donor macrovesicular steatosis was not significantly associated with GS in any time period.

Sensitivity analyses

Sensitivity analyses (Table 4) confirmed the association of Mas30 grafts on GS in MASLD recipients across multiple analytic scenarios. Across donor-related sensitivity analyses, Mas30 grafts consistently demonstrated significantly worse GS when excluding donors with cardiometabolic risk factors (early: aHR 2.58, P=0.02; long-term: aHR 1.88, P=0.048), excluding extended criteria donors (early: aHR 2.93, P<0.001; long-term: aHR 1.78, P=0.002), and restricting to DCD donors (early: aHR 4.22, P<0.001; long-term: aHR 2.47, P<0.001). Notably, the association was most pronounced among DCD donors, with a more than fourfold increase in early mortality risk.

Recipient-related sensitivity analyses yielded similar findings. The hazard of Mas30 grafts on MASLD recipients remained significant when restricting to recipients younger than 50 years (early: aHR 2.80, P<0.001; long-term: aHR 1.63, P=0.004), excluding recipients with MELD score >30 (early: aHR 3.11, P<0.001; long-term: aHR 1.70, P=0.002), excluding recipients with hepatocellular carcinoma (early: aHR 3.27, P<0.001; long-term: aHR 1.65, P=0.01), and excluding recipient cardiovascular deaths (early: aHR 3.12, P<0.001; long-term: aHR 1.68, P=0.004).

Competing risk analyses

Competing risk analyses using Fine-Gray subdistribution hazard models further corroborated these findings (Table 4). When treating non-graft deaths as a competing event, Mas30 grafts were independently associated with worse GS in MASLD recipients across the early [subdistribution hazard ratio (sHR) 3.18, P=0.001], intermediate (sHR 2.55, P=0.003), and long-term periods (sHR 2.18, P=0.01). Similarly, when treating cardiovascular deaths as a competing event, the hazard of Mas30 grafts remained significant across the early (sHR 2.75, P<0.001), intermediate (sHR 2.01, P=0.001), and long-term periods (sHR 1.51, P=0.03) (Figure S6).

Discussion

Our study demonstrates that Mas30 grafts were associated with reduced early GS among all patients transplanted for SLD, without persistent effects beyond 1 year. However, stratification by disease etiology revealed persistent survival differences in patients with MASLD, with reduced short- and long- term survival in recipients of Mas30 grafts, even after adjustment for MP. Recipients with MetALD and ALD receiving a Mas30 graft had preserved GS in all the studied follow-up periods. These findings highlight the importance of carefully integrating both donor and recipient metabolic profiles when matching donors and recipients.

Across our cohort, donors with Mas30 were younger, more likely to be Hispanic, with higher BMI, and worse alcohol use disorder. Although younger age typically favors GS, BMI, alcohol use, and ethnic differences may offset that advantage (24-26). Obesity impairs GS, and Hispanic ethnicity similarly increases steatosis risk and worsens graft outcomes compared with White donors (27,28). Importantly, our results remained robust when adjusting for these variables, suggesting the association with reduced GS is independent of donor-related risk factors to better inform decisions regarding the use of steatotic grafts.

An unexpected finding we observed was the reduced prevalence of Mas30 grafts over time, particularly from 2022 to 2024. This decline likely reflects the increased deceased donor availability (21), the absence of evidence-based guidelines endorsing Mas30 graft use and barriers to access novel defatting strategies, such as MP (16,29). Furthermore, the acuity circle-based allocation model may have contributed to this decline, as broader organ sharing has been associated with increased cold ischemia times and decreased utilization of marginal grafts, potentially disproportionately affecting high-risk organs such as Mas30 grafts (30). Although providers recognize that MP can improve organ quality, nearly two-thirds report substantial barriers to its implementation (15). Among U.S. providers, the most frequently cited obstacles were insufficient institutional support for MP, followed by limited funding and inadequate staffing (31). These hurdles highlight key targets for intervention to help expand the use of macrovesicular steatotic liver donors.

Geographic variation in the use of Mas30 grafts appears to reflect varying regional donor-recipient demographics and institutional practice policies. Prior national analyses suggest this pattern may reflect center-level expertise, as high-volume transplant systems are more likely to accept and successfully manage a greater proportion of extended-criteria grafts in order to widen organ availability (32). The Southern region encompasses most high-volume LT centers, which may explain the greater organ utilization in this region (33). In addition, the Midwest has one of the nation’s highest burdens of metabolic disease, increasing the likelihood of steatotic donor livers entering the local organ pool (34). Together, these factors likely contribute to the observed regional concentration of steatotic graft utilization.

Our study demonstrated that Mas30 grafts were associated with reduced post-LT GS among recipients with MASLD, with robust estimates across models. These findings suggest that recipients with MASLD may be uniquely vulnerable to highly steatotic liver grafts. Similar to our results, a previous UNOS study reported reduced 30-day and one-year GS among patients with NAFLD receiving Mas30 grafts compared to matched non-NAFLD recipients, with no differences in five or 10-year GS, which may be explained, in part, by inclusion of MetALD within the NAFLD cohort (35). Unlike the previously mentioned study, our analysis provides a more contemporary evaluation, applies the 2023 Delphi consensus nomenclature, and incorporates robust sensitivity analyses demonstrating that this adverse association is confined exclusively to recipients with MASLD. The mechanisms underlying this heightened risk are not fully understood but may relate to the greater visceral adiposity, insulin resistance, vascular dysfunction, and systemic inflammation characteristic of MASLD (36). These factors can impair recovery from ischemia-reperfusion injury, which worsens as graft steatosis increases (37).

Interestingly, adjustment for obesity and diabetes in our study did not substantially attenuate the association of Mas30 grafts and GS although they were each independent factors associated with GS in early and long-term periods, respectively. This suggests that visceral adiposity and insulin resistance alone may not fully explain the connection between Mas30 grafts and reduced GS, consistent with a recent meta-analysis showing no adverse effect of donors with obesity on graft or patient outcomes (38). In contrast, a study from Europe, with 12,147 patients demonstrated that donors with diabetes have higher post-LT mortality independent of graft steatosis, indicating heterogeneity in the metabolic contributors to post-LT risk (39). Lean mass, which has been shown to be lower in MASLD post-LT, may also be a relevant factor. Lower lean mass may reduce insulin sensitivity and contribute to worse outcomes, despite diabetes not reaching statistical significance in our cohort (40). Further investigation is needed to clarify these mechanisms.

In contrast, recipients with MetALD and ALD showed no significant association between donor steatosis and post-LT GS in multivariable analyses, suggesting that steatotic grafts, including those with Mas30, may be safely used in these populations. This may be due to a reduction of alcohol intake, which is the primary driver of ongoing liver injury in these patients, as compared to recipients with MASLD, who maintain their metabolic milieu post–LT. Evidence from prior research aligns with our results, demonstrating that GS in recipients with MetALD and ALD is not significantly impaired, provided alcohol relapse is avoided (41). These findings highlight that the impact of graft steatosis on outcomes varies by SLD subtype and support the safe utilization of steatotic liver grafts in candidates with MetALD and ALD regardless of steatosis severity.

Our study had several limitations and strengths. The UNOS database is a national database that lacks granularity, particularly regarding cardiovascular risk factors, and while it contains variables for causes of graft dysfunction, these fields are inconsistently populated and unreliable for accurate cause-specific adjudication of graft loss. Furthermore, the classification of recipients into three SLD subtypes using diagnostic codes is inherently limited by the non-granular nature of registry data, which may introduce misclassification bias and affect the precision of our subgroup analyses. We acknowledge that the degree of macrovesicular infiltration may be underrepresented in the UNOS database because not all donor livers are biopsied, and when biopsies are performed, the assessment lacks standardization across centers (42). Moreover, our cohort might be enriched for donors where the team was concerned enough to biopsy, and therefore may not reflect the real spectrum of the general deceased donor population. Notably, our findings remained robust after excluding HCC recipients, mitigating concerns about potential confounding by transplant indication. In regards to MP, utilization remained below 2% during most of the analyzed period, precluding a meaningful subgroup analysis of its effect in MASLD recipients of Mas30 grafts.

Despite the mentioned limitations, a key strength of our study lies in the use of a robust and large sample size, which allowed us to obtain a sizable cohort of donors and recipients across the SLD strata. We adjusted for multiple confounding factors to achieve reliable multivariable analysis results and evaluate if the impact was solely dependent on the macrovesicular deposition rather than inherent baseline donor risk. We also performed multiple sensitive analyses and a competitive risk analysis to increase the robustness of our findings. Emerging strategies for MASLD recipients receiving Mas30 grafts include normothermic machine perfusion (NMP) to mitigate ischemia-reperfusion injury and early allograft dysfunction (43), glucagon-like peptide-1 (GLP-1) receptor agonists and concurrent sleeve gastrectomy aimed to reduce metabolic risk factors and reduce acquired allograft steatosis (44,45), all warranting future studies in this setting.

Conclusions

In this registry-based analysis, Mas30 grafts were associated with a nearly threefold higher early graft failure risk in MASLD recipients, extending to 3 years post-LT and independent of MP, while MetALD and ALD recipients remained unaffected. These associations support etiology-specific allocation strategies and systematic donor steatosis assessment to safely expand the use of these high-risk grafts. Future studies analyzing more granular outcome data and emerging therapies are needed to confirm these findings.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2026-0143/rc

Peer Review File: Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2026-0143/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2026-0143/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The Cleveland Clinic Foundation and Virginia Commonwealth University deemed the UNOS/OPTN database as publicly available, de-identified data; therefore, institutional review board (IRB) approval was not required, and individual informed consent was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Paik JM, Hobbs K, Gupta A, et al. Prevalence of MASLD, Met-ALD, and ALD and Associated Fibrosis Among US Adults: Insights From NHANES 2017 to 2023. J Clin Gastroenterol 2025; Epub ahead of print. [Crossref] [PubMed]
2. Kalligeros M, Vassilopoulos A, Vassilopoulos S, et al. Prevalence of Steatotic Liver Disease (MASLD, MetALD, and ALD) in the United States: NHANES 2017-2020. Clin Gastroenterol Hepatol 2024;22:1330-1332.e4. [Crossref] [PubMed]
3. Targher G, Valenti L, Byrne CD. Metabolic Dysfunction-Associated Steatotic Liver Disease. N Engl J Med 2025;393:683-98. [Crossref] [PubMed]
4. Tilg H, Petta S, Stefan N, et al. Metabolic Dysfunction-Associated Steatotic Liver Disease in Adults: A Review. JAMA 2026;335:163-74. [Crossref] [PubMed]
5. Simonetto DA, Shah VH, Kamath PS. Outpatient management of alcohol-related liver disease. Lancet Gastroenterol Hepatol 2020;5:485-93. [Crossref] [PubMed]
6. Crabb DW, Bataller R, Chalasani NP, et al. Standard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia. Gastroenterology 2016;150:785-90. [Crossref] [PubMed]
7. Choi WT, Jen KY, Wang D, et al. Donor Liver Small Droplet Macrovesicular Steatosis Is Associated With Increased Risk for Recipient Allograft Rejection. Am J Surg Pathol 2017;41:365-73. [Crossref] [PubMed]
8. Kikuchi AT, Akanuma N, Choi WT, et al. Assessment of large droplet fat in frozen sections of donor liver biopsies: utility and interobserver variability of the newly described Banff method compared to a simplified Average of Fields method. J Clin Pathol 2024;77:151-6. [Crossref] [PubMed]
9. Trapero-Marugán M, Little EC, Berenguer M. Stretching the boundaries for liver transplant in the 21st century. Lancet Gastroenterol Hepatol 2018;3:803-11. [Crossref] [PubMed]
10. Kwong AJ, Kim WR, Lake J, et al. Impact of Donor Liver Macrovesicular Steatosis on Deceased Donor Yield and Posttransplant Outcome. Transplantation 2023;107:405-9. [Crossref] [PubMed]
11. Jackson KR, Motter JD, Haugen CE, et al. Temporal trends in utilization and outcomes of steatotic donor livers in the United States. Am J Transplant 2020;20:855-63. [Crossref] [PubMed]
12. Akabane M, Imaoka Y, Esquivel CO, et al. Overcoming the hurdles of steatotic grafts in liver transplantation: Insights into survival and prognostic factors. Liver Transpl 2024;30:376-85. [Crossref] [PubMed]
13. Chavin KD, Taber DJ, Norcross M, et al. Safe use of highly steatotic livers by utilizing a donor/recipient clinical algorithm. Clin Transplant 2013;27:732-41. [Crossref] [PubMed]
14. Linares I, Hamar M, Selzner N, et al. Steatosis in Liver Transplantation: Current Limitations and Future Strategies. Transplantation 2019;103:78-90. [Crossref] [PubMed]
15. Parente A, Tirotta F, Pini A, et al. Machine perfusion techniques for liver transplantation - A meta-analysis of the first seven randomized-controlled trials. J Hepatol 2023;79:1201-13. [Crossref] [PubMed]
16. Cywes C, Banker A, Muñoz N, et al. The Potential Utilization of Machine Perfusion to Increase Transplantation of Macrosteatotic Livers. Transplantation 2024;108:e370-5. [Crossref] [PubMed]
17. Ochoa-Allemant P, Serper M, Wang RX, et al. Waitlisting and liver transplantation for MetALD in the United States: An analysis of the UNOS national registry. Hepatology 2025;81:532-45. [Crossref] [PubMed]
18. Vodkin I, Kuo A. Extended Criteria Donors in Liver Transplantation. Clin Liver Dis 2017;21:289-301. [Crossref] [PubMed]
19. Dutkowski P, Schlegel A, Slankamenac K, et al. The use of fatty liver grafts in modern allocation systems: risk assessment by the balance of risk (BAR) score. Ann Surg 2012;256:861-8; discussion 868-9. [Crossref] [PubMed]
20. Long MT, Noureddin M, Lim JK. AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals: Expert Review. Gastroenterology 2022;163:764-774.e1. [Crossref] [PubMed]
21. OPTN/SRTR 2023 annual data report: Preface. Am J Transplant 2025;25:S1-10. [Crossref]
22. Feng S, Goodrich NP, Bragg-Gresham JL, et al. Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transplant 2006;6:783-90. [Crossref] [PubMed]
23. Kim NG, Sharma A, Saab S. Cardiovascular and metabolic disease in the liver transplant recipient. Best Pract Res Clin Gastroenterol 2020;46-47:101683. [Crossref] [PubMed]
24. Min EK, Lee JG, Choi Y, et al. Navigating the risk of living donor liver transplantation from older donors: analysis of 4035 cases from a multicenter cohort. Int J Surg 2026;112:1211-8. [Crossref] [PubMed]
25. Yeow M, Pang NQ, Muthiah MD, et al. Impact of donor age on recipient morbidity and mortality after living donor liver transplantation. ANZ J Surg 2022;92:1867-72. [Crossref] [PubMed]
26. Kubota T, Hata K, Sozu T, et al. Impact of Donor Age on Recipient Survival in Adult-to-Adult Living-donor Liver Transplantation. Ann Surg 2018;267:1126-33. [Crossref] [PubMed]
27. Carrion AF, Ghanta R, Carrasquillo O, et al. Chronic liver disease in the Hispanic population of the United States. Clin Gastroenterol Hepatol 2011;9:834-41; quiz e109-10. [Crossref] [PubMed]
28. Goyes D, Niezen S, Rubianes-Guerrero MG, et al. Acculturation and hepatic steatosis among individuals of Hispanic ancestry. Clin Liver Dis (Hoboken) 2024;23:e0240. [Crossref] [PubMed]
29. Gedallovich SM, Ladner DP, VanWagner LB. Liver transplantation in the era of non-alcoholic fatty liver disease/metabolic (dysfunction) associated fatty liver disease: the dilemma of the steatotic liver graft on transplantation and recipient survival. Hepatobiliary Surg Nutr 2022;11:425-9. [Crossref] [PubMed]
30. Sandhu S, Goldberg D. Update on Organ Allocation and Liver Transplantation. Gastroenterol Hepatol (N Y) 2025;21:424-30. [PubMed]
31. Parente A, Flores Carvalho M, Panconesi R, et al. Trends and Obstacles to Implement Dynamic Perfusion Concepts for Clinical Liver Transplantation: Results from a Global Web-Based Survey. J Clin Med 2023;12:3765. [Crossref] [PubMed]
32. Volk ML, Reichert HA, Lok AS, et al. Variation in organ quality between liver transplant centers. Am J Transplant 2011;11:958-64. [Crossref] [PubMed]
33. Cholankeril G, Perumpail RB, Tulu Z, et al. Trends in Liver Transplantation Multiple Listing Practices Associated With Disparities in Donor Availability: An Endless Pursuit to Implement the Final Rule. Gastroenterology 2016;151:382-386.e2. [Crossref] [PubMed]
34. Jones-Carr ME, Dayala H, McLeod MC, et al. Geographic variation in utilization of deceased donor livers in the United States in the era of advanced perfusion. Liver Transpl 2026;32:46-54. [Crossref] [PubMed]
35. Altshuler PJ, Dang H, Frank AM, et al. Evaluating Outcomes Related to Donor and Recipient Metabolic Environment: Macrosteatotic Allografts and Nonalcoholic Steatohepatitis. Liver Transpl 2022;28:623-35. [Crossref] [PubMed]
36. Sato-Espinoza K, Chotiprasidhi P, Liza E, et al. Evolution of liver transplantation in the metabolic dysfunction-associated steatotic liver disease era: Tracking impact through time. World J Transplant 2024;14:98718. [Crossref] [PubMed]
37. Peralta C, Jiménez-Castro MB, Gracia-Sancho J. Hepatic ischemia and reperfusion injury: effects on the liver sinusoidal milieu. J Hepatol 2013;59:1094-106. [Crossref] [PubMed]
38. Alnagar AMT, Hajibandeh S, Hajibandeh S, et al. Impact of Donor Obesity on Graft and Recipient Survival Outcomes After Liver Transplantation: A Systematic Review and Meta-analysis. Transplant Direct 2024;10:e1656. [Crossref] [PubMed]
39. Sonneveld MJ, Parouei F, den Hoed C, et al. Graft Steatosis and Donor Diabetes Mellitus Additively Impact on Recipient Outcomes After Liver Transplantation-A European Registry Study. Clin Transplant 2024;38:e15437. [Crossref] [PubMed]
40. Cardoso A, Ferreira SC, Araújo MA, et al. Association between body composition, eating behavior, dietary intake, and metabolic dysfunction-associated steatotic liver disease in liver transplant recipients. Clin Nutr 2025;52:154-61. [Crossref] [PubMed]
41. Erard D, Villeret F, Chouik Y, et al. Dual alcohol and metabolic-related liver disease: Results from a population of liver transplant patients. Liver Int 2024;44:422-32. [Crossref] [PubMed]
42. Wang BK, Chen AY, Prasadh J, et al. A contemporary analysis of 20,086 deceased donor liver biopsies. World J Surg 2024;48:437-45. [Crossref] [PubMed]
43. Zhang M, Nguyen M, Mao S, et al. Ex situ normothermic machine perfusion reduces postreperfusion syndrome and improves patient and graft survival following liver transplant using macrosteatotic liver grafts. Am J Transplant 2026;26:830-40. [Crossref] [PubMed]
44. Larson EL, Ellias SD, Blezek DJ, et al. Simultaneous liver transplant and sleeve gastrectomy provides durable weight loss, improves metabolic syndrome and reduces allograft steatosis. J Hepatol 2025;83:729-37. [Crossref] [PubMed]
45. Kanwal F, Kramer JR, Li L, et al. GLP-1 Receptor Agonists and Risk for Cirrhosis and Related Complications in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease. JAMA Intern Med 2024;184:1314-23. [Crossref] [PubMed]