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Llamoza-Torres et al. Metab Target Organ Damage 2024;4:40 https://dx.doi.org/10.20517/mtod.2024.64 Page 5 of 18

In the context of LT, Wong et al. presented registry data from the United Network for Organ Sharing
[52]
(UNOS) covering the period from 2002 to 2012 . The data revealed the prevalence of T2DM across
different etiological groups: 12.6% for ALD, 13.6% for HCV, increasing to 24.0% in patients with HCC, and
[52]
35.5% in those with metabolic-associated steatohepatitis (MASH) . Furthermore, patients with MASH had
higher post-transplant survival [hazard ratio (HR) = 0.69; 95%CI: 0.63-0.77] and lower risk of graft loss (HR
= 0.76; 95%CI: 0.69-0.83) compared with those with viral etiology or HCC, despite higher rates of body mass
index (BMI), T2DM, and cardiovascular disease . Conversely, data from the European Liver Transplant
[52]
Registry presented in 2019 showed no significant difference in post-transplant survival (HR = 1.10; 95%CI:
0.97-1.24) or graft survival (HR = 1.02; 95%CI: 0.90-1.15) between MASH and other etiologies . HCC was
[53]
more common among recipients transplanted for MASH (39.1% vs. 28.9%, P < 0.001). This registry did not
[53]
determine the prevalence of T2DM .
In addition, the characteristics of the donor should not be overlooked. Zamora-Olaya et al. from the Reina
Sofía University Hospital (Córdoba, Spain) demonstrated that atheromatosis of the donor's hepatic artery is
an independent risk factor for the development of hepatic artery thrombosis (OR = 17.79; P = 0.008) .
[54]
Evaluation of atherosclerosis is not usually performed routinely in donor assessments. Donors are usually
older than transplant candidates, and their most frequent cause of death is cerebrovascular disease, which
confers them an inherent adverse metabolic profile. In this series of patients , the prevalence of hepatic
[54]
steatosis between donors with and without atherosclerosis of the hepatic artery was not different. However,
if we consider hepatic artery atheromatosis as a surrogate marker of metabolic dysfunction, this subtype of
[54]
dysfunction could be inferred. On the other hand, in this same series , the authors describe an unexpected
protective factor of ALD against the development of hepatic artery thrombosis (OR = 0.24; 95%CI: 0.06-
0.97; P = 0.046), in contrast to the absence of influence from the etiology of liver disease on the development
of artery thrombosis. However, they point out that most of these studies were carried out before the
redefinition of the MASLD/MetALD concepts, and this absence of association must be confirmed in
prospective series.

Holzner et al. reported one of the largest single-center series of LT for MASH-related HCC (MASH-HCC)
[55]
from Mount Sinai Medical Center . They evaluated data from 2001 to 2017, comparing MASH-HCC (n =
51) with non-MASH-HCC (n = 584), and found no significant differences in OS and RFS. This case study
analyzed the tumor risk characteristics of the explant and found no significant differences between MASH-
HCC and non-MASH-HCC, except for a greater amount of viable tumor tissue in the MASH-HCC group
[55]
(3 vs. 1, P < 0.001) . This contrasts with previous reports [56,57] , which noted fewer high-risk features
associated with MASH-HCC in the histological study of the explant. High-risk tumor features included:
more than 3 tumors, the largest tumor size greater than 5 cm, the presence of vascular invasion, the
presence of metastases, and poor tumor differentiation. Although most reported series conclude that there
are no significant differences in the post-transplant outcomes between MASH-HCC and non-MASH-
HCC [52,53,55-57] , these conclusions should be interpreted with caution. The metabolic morbidity associated
with MASLD may influence post-surgical complications or the type of tumor recurrence , particularly in
[58]
[59]
the understaged subgroup (especially in cases where understaging occurs following treatment with
checkpoint inhibitors).

Sadler et al., evaluating a cohort of MASH-HCC vs. non-MASH-HCC patients at two reference centers,
found that MASH status was a protective factor against recurrence in patients with tumors beyond Milan
criteria (HR = 0.21; 95%CI: 0.05-0.86; P = 0.029) . Although the difference in the proportion of patients
[59]
with microvascular invasion between the MASH group (57.9%) and the non-MASH group (36.6%) was not
statistically significant (P = 0.07), it highlights a difference in tumor biology . Notably, in the MASH-HCC
[59]