Inferior Long-Term Outcome of Fatty Liver Allografts After Orthotopic Liver Transplantation

Abstract

Background

Liver transplantation remains the only curative treatment modality for patients with end-stage liver disease. The worldwide shortage of donor organs has contributed to the use of fatty livers. However, the long-term survival of recipients who underwent transplantation with fatty livers remains unclear.

Material/Methods

All orthotopic liver transplantations (OLT) conducted from January 1, 2002, to December 31, 2013, at Hannover Medical School were primarily included (N=337). The assessment of hepatic steatosis was based mainly on histopathology of biopsies, but also included ultrasound and computed tomography imaging and macroscopic organ evaluation. The data were retrospectively analyzed using univariable and multivariable regression analyses and Kaplan-Meier statistics.

Results

Kaplan-Meier statistics demonstrated a significantly reduced long-term survival for orthotopic liver transplantation of fatty liver allografts, mainly due to increased initial cellular damage and early (in-house) mortality. In the multivariate Cox regression analysis, recipient age (P=0.007; hazard ratio [HR], 1.027); occurrence of postoperative complications (P=0.001; HR, 2.187), and allograft steatosis (P=0.041; HR, 1.427) were independently associated with inferior survival.

Conclusions

The results identify fatty liver allografts as an independent risk factor associated with reduced short- and long-term survival after orthotopic liver transplantation. These findings highlight the necessity for strategies to improve outcomes and triggers additional research in the field of organ preservation.

Introduction

Orthotopic liver transplantation (OLT) remains the only curative treatment modality for patients with end-stage liver disease, such as alcohol-related cirrhosis, hepatocellular carcinoma, and nonalcoholic steatohepatitis [1–3]. However, the number of patients awaiting liver transplantation continues to rise, while the availability of suitable donor organs remains limited. According to the German Organ Transplantation Foundation (Deutsche Stiftung Organspende), in 2023, a total of 2095 patients were on the waiting list for OLT. However, only 868 liver transplantations were performed [4]. This persistent imbalance highlights the urgent need to expand the donor pool and improve graft utilization.

To address this, extended criteria for the donor have been developed, and the use of marginal grafts has become an important strategy to increase the number of transplantable organs [5,6]. The Eurotransplant definition includes variables such as donor age over 65 years, intensive care unit stay longer than 7 days with ventilation, body mass index (BMI) higher than 30 kg/m2, hepatic steatosis higher than 40%, and elevated serum sodium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels [7]. Among these, hepatic steatosis is the most prevalent and clinically relevant component in the spectrum of extended criteria for the donor livers [1,8].

With the increasing incidence and prevalence of non-alcoholic fatty liver disease, the prevalence of steatotic donor organs is also rising, emphasizing the need for strategies for a more effective assessment of the quality of fatty liver allografts and the suitability for transplantation [9].

The presence of hepatic fat has a profound effect on graft performance following OLT, primarily through enhanced susceptibility to ischemia-reperfusion (I/R) injury. Fat accumulation disrupts hepatic microcirculation exacerbating vulnerability to ischemia and subsequent reperfusion-related injury [6,10,11]. Hence, the risk for delayed graft function, primary non-function, and ischemic-type biliary lesions after OLT is increases [5,7,12,13].

Mechanistically, I/R injury involves an initial interruption of blood flow with adenosine triphosphate (ATP) depletion and hepatocellular swelling, followed by reperfusion-induced damage through the generation of reactive oxygen species, inflammatory mediators, and vasoconstrictor mechanisms [12,14,15]. This cascade can result in parenchymal cell death, microcirculatory failure, and systemic inflammatory immune response [12,16].

In particular, steatotic livers demonstrate diminished antioxidant capacity, increased mitochondrial vulnerability, and excessive reactive oxygen species production, making them more susceptible to oxidative stress [2,17]. In addition, microvascular alterations, such as sinusoidal narrowing caused by lipid-laden hepatocytes, contribute to chronic hypoxia, ATP depletion, and increased leucocyte adhesion. This leads to sinusoidal constriction, reduced hepatic perfusion, and ultimately impaired graft function [9,18,19]. As a result, recipients of fatty liver allografts often develop elevated levels of AST and ALT after OLT, reflecting hepatocellular damage, and this potentially leads to inferior graft function or even higher rates of primary non-function [10,20]. Importantly, hepatic steatosis is considered a major risk factor for primary non-function and significantly worsens post-transplant outcomes, even in cases in which urgent re-transplantation is performed [21].

Although the short-term complications and risks associated with steatotic grafts are well described, the effect of hepatic steatosis on long-term outcomes after OLT remains insufficiently understood.

It remains uncertain whether fatty liver grafts affect only the early postoperative phase or also compromise long-term patient and graft survival.

Therefore, the aim of this study is to assess the morbidity, mortality, and long-term survival of recipients of fatty liver allografts, compared with recipients of grafts without significant steatosis. Furthermore, the study aims to improve understanding of the assessment and utilization of marginal organs that might otherwise been primarily rejected, with particular focus on potential organ preservation and regeneration strategies through cold or warm machine perfusion – approaches intended to mitigate the effects of I/R injury and reduce complications associated with OLT of steatotic allografts.

Material and Methods

Study Design and Patient Cohort

This was a retrospective, single-center investigation. All OLTs performed at the study center from January 1, 2002, to December 31, 2013, were primarily included. Patients who received non-steatotic grafts served as a control group (group A), and recipients of steatotic liver grafts constituted the study group (group B). The study was approved by the Hannover Medical School’s Institutional Ethics Board by Dr. Ulf Kulik (reference 2468-2014). Pediatric and re-transplantations were excluded. A minimum follow-up duration of 5 years was established for the evaluation of long-term survival (Figure 1).

Figure 1.

Study cohort and patient selection.

Definition and Assessment of Hepatic Steatosis

Hepatic steatosis in the donor liver was identified based on 1 or more of the following: ultrasound imaging prior to donor surgery, macroscopic assessment during organ procurement, or histopathological examination of donor liver biopsies. Regarding ultrasound evaluation, a liver was considered steatotic if there was increased echogenicity, poor visualization of intrahepatic vessels, attenuation of the ultrasound beam, hepatomegaly, and/or loss of diaphragm clarity. The intraoperative assessment was based on color and appearance, consistency, size, capsular changes, and the presence of surface oozing or fragility. The evaluation was based only on the external medical results, since the original imaging data of both the ultrasound and CT scans were not available in the Eurotransplant database. The diagnostic criterion for histological confirmation of hepatic steatosis was defined as the presence of triglyceride-rich macrovesicular and/or microvesicular lipid droplets within the hepatocytes, accounting for at least 5% of the total liver weight [22]. Owing to the retrospective nature of the study and the presumed interobserver variability in the donor hospitals, surgeons, and pathologists, further grading of the severity of steatosis was not performed.

Data Collection and Endpoints

Clinical and donor-related data were provided by Eurotransplant; data regarding the recipient, OLT surgery protocols, and postoperative course were obtained from the clinical documentation systems. The primary endpoint was long-term survival following OLT using fatty liver allografts.

Statistical Analysis

Comparisons of different groups were conducted using the t test, while recipient survival was analyzed using the Kaplan-Meier method. Moreover, multivariate Cox regression analyses were performed to evaluate independent variables that influenced long-term survival. Therefore, we included variables such as age, insulin treatment, cold ischemia time, and duration of surgery, which prior studies have similarly identified as factors affecting graft function [20,23,24]. Allstatistical analyses were conducted using SPSS, statistical significance was defined as a P value <0.05.

Results

Study Cohort

In total, the study included 337 patients who underwent OLT. The first group (group A) consisted of 205 patients who underwent OLT with no signs of steatosis in the graft. The second group (group B) included 132 patients who underwent OLT using fatty liver allografts. In 54% of cases in the steatosis group, the diagnosis was confirmed histologically via biopsy. The remaining cases were classified based on sonographic findings or macroscopic assessment at organ procurement. Among cases in which either sonographic or procurement findings were available, the presence of steatosis correlated with the biopsy-confirmed diagnosis in approximately 70% of cases. In more than 70% of the biopsy-confirmed cases, macrovesicular steatosis was present.

Clinical Characteristics and OLT

Table 1 provides an overview of the recipient and donor characteristics. In summary, most variables, including various indications for OLT and the model for end-stage liver disease score, were comparable between groups. The only notable difference was a shorter time on the waiting list in group B (239 vs 179). It should be mentioned that at the start of the observation period, plasmatic coagulation was primarily assessed using the Quick value, which cannot be converted into the international normalized ratio. Consequently, the calculated model for end-stage liver disease scores showed a higher percentage of missing values. While most variables were comparable, donors in group B displayed a slightly higher median BMI (26.0 vs 28.0), as well as elevated levels of transaminases (AST, 38.0 vs 44.0; ALT, 30.0 vs 32.0) and sodium, without statistical significance (147.0 vs 149.0). Regarding the OLT procedure itself, recipients of group B developed higher rates of primary non-function than did those in group A (15.2% vs 8.8%, P<0.001) and more frequently required re-transplantation (11.4% vs 6.3%, P=0.001).

Table 1.

Comparison of recipient and donor clinical data of donor recipients receiving grafts without (group A) and with (group B) steatosis.

Liver transplantation (OLT) N=337	No signs of steatosis in graft (group A) n=205 Median (range) or n (%)	Missing values	Steatosis in graft (group B) n=132 Median (range) or n (%)	Missing values N (%)	P value Chi2 test
Recipient clinical data
Female	85 (41.5%)	0 (0%)	49 (37.1%)	0 (0%)	0.104
Male	120 (58.5%)	0 (0%)	83 (62.9%)	0 (0%)
Age (years)	50.0 (19–73)	0 (0%)	53.0 (23–69)	0 (0%)	0.420
BMI	25.0 (17–42)	3 (1.5%)	25.5 (17.7–39.5)	1 (0.75%)	0.269
Indication for OLT
Ethyl-tox/crypt. cirrhosis	41 (20.0%)	0 (0%)	21 (15.9%)	0 (0%)	0.098
HBV-/HCV-related cirrhosis	23 (11.2%)		16 (12.1%)
HCC/NEC-Metastases	43 (21.0%)		44 (33.3%)
PSC/PBC	37 (18.0%)		20 (15.2%)
(Sub-)Acute liver failure	27 (13.2%)		11 (8.3%)
Others	34 (16.6%)		20 (15.2%)
Laboratory MELD	16.9 (5–40)	50 (24.4%)	14.6 (7–40)	31 (23.5%)	0.568
Time on waiting list	239.0 (1–40769)	0 (0%)	179.0 (1–38865)	0 (0%)	0.195
Encephalopathy (yes)	57 (27.8%)	0 (0%)	34 (28.8%)	4 (3.1%)	0.620
Hemodialysis pre-OLT (yes)	22 (10.8%)	2 (1.0%)	18 (13.6%)	4 (3.1%)	0.083
Respirator treatment pre-OLT (yes)	14 (6.9%)	2 (1.0%)	6 (4.5%)	5 (3.8%)	0.106
Donor data
Female	95 (46.3%)	0 (0%)	51 (38.6%)	0 (0%)	0.104
Male	110 (53.7%)		81 (61.4%)
Age (years)	50.0 (16–88)	1 (0.5%)	54.0 (18–78)	2 (1.5%)	<0.001
BMI	26.0 (16–46)	1 (0.5%)	28.0 (19–55)	2 (1.5%)	0.386
IDDM/NIDDM	16 (7.8%)	2 (1.0%)	17 (12.9%)	2 (1.5%)	0.002
Insulin treatment	64 (31.2%)	0 (0%)	34 (25.8%)	4 (3.1%)	0.056
ICU stay (days)	4.0 (1–41)	2 (1.0%)	4.0 (1–24)	3 (2.3%)	0.608
AST (U/L)	38.0 (1–1623)	4 (2.0%)	44.0 (11–831)	7 (5.3%)	0.929
ALT (U/L)	30.0 (0–821)	3 (1.5%)	32.0 (6–584)	3 (2.3%)	0.946
Sodium (mmol/L)	147.0 (129–197)	2 (1.0%)	149.0 (132–189)	2 (1.5%)	0.602
CIT (min)	616.5 (222–1969)	5 (2.4%)	581.0 (310–1174)	6 (4.5%)	0.069
Duration of surgery	200.0 (108–434)	4 (2.0%)	212.0 (118–405)	3 (2.3%)	0.372
Primary abdominal closure (yes)	165 (81.7%)	3 (1.5%)	90 (68.2%)	4 (3.1%)	<0.001
Complications graded Dindo ≥3	157 (76.6%)	0 (0%)	97 (73.5%)	0 (0%)	0.205
Primary nonfunction	18 (8.8%)	0 (0%)	20 (15.2%)	0 (0%)	<0.001
Re-OLT	13 (6.3%)	0 (0%)	15 (11.4%)	0 (0%)	0.001
ICU stay (days)	11 (1–187)	0 (0%)	13 (1–277)	0 (0%)	0.078
Hospital stay (days)	33 (1–202)	0 (0%)	36.5 (1–277)	0 (0%)	0.116
In-house mortality	25 (12.2%)	0 (0%)	27 (20.5%)	0 (0%)	<0.001

BMI – body mass index; AST – aspartate aminotransferase; OLT – orthotopic liver transplantation; MELD – model for end-stage liver disease; ICU – intensive care unit; CIT – cold ischemia time; HCC/NEC – hepatocellular carcinoma/neuroendocrine; PCS/PBC – primary sclerosing cholangitis/primary biliary cholangitis; IDDM – insulin-dependent diabetes mellitus; NIDDM – non–insulin-dependent diabetes mellitus.

Liver Function Tests

Figure 2 provides an overview of the laboratory values obtained after surgery. AST, ALT, and glutamate dehydrogenase (GLDH) values were collected from the first to the third postoperative day (POD), with the values determined 12 hours after OLT considered as POD 1. Significantly increased levels of GLDH in group B were detected on all PODs (P<0.001). Furthermore, group B showed significantly higher levels of AST (POD1, P<0.001; POD2, P=0.033; POD3, P=0.042).

Figure 2.

Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutamate dehydrogenase (GLDH) values obtained after orthotopic liver transplantation on postoperative day (POD) 1, 2, and 3.

Survival Statistic

Kaplan-Meier analysis demonstrated significantly reduced survival among patients who underwent OLT with fatty liver allografts (group B, P<0.001). As displayed in Figure 3, the reduction in survival is primarily attributed to an increase in early (in-house) mortality, which was significantly elevated in group B (20.5% vs 12.2%, P<0.001). Subsequently, the survival curves seem to follow a nearly parallel trajectory.

Figure 3.

Results of Kaplan-Meier for survival after orthotopic liver transplantation using fatty and non-fatty liver allografts.

Univariable and Multivariable Cox Regression

To identify factors with independent influence on the overall survival univariable and multivariable Cox regression analyses were performed. Univariable regression analyses revealed the following potential factors affecting overall survival: recipient age (P<0.001; HR 1.036), indication for OLT (ie, hepatocellular carcinoma/neuroendocrine metastases (P=0.011; HR, 0.576), primary sclerosing cholangitis/primary biliary cholangitis (P<0.001; HR, 0.324), (sub-)acute liver failure (P=0.001; HR, 0.331), history of hemodialysis before OLT (P=0.040; HR, 1.609), utilization of fatty liver allografts (P<0.001; HR, 1.749), primary abdominal closure after surgery (P=0.002; HR, 1.732), length of stay in intensive care unit (P<0.001; HR, 1.007), and overall hospital stay (P=0.035; HR, 1.004).

In the multivariable Cox regression analysis, recipient age (P=0.007; HR, 1.027), indication for transplantation, such as hepatocellular carcinoma/neuroendocrine metastases (P=0.005; HR, 0.533), primary sclerosing cholangitis/primary biliary cholangitis (P=0.007; HR, 0.457), (sub-) acute liver failure (P=0.003; HR, 0.331), and steatosis in the allograft (P=0.041; HR, 1.427) were associated with inferior or improved survival. The above indications for OLT were linked to enhanced recipient survival. On the other hand, advanced age and steatosis in the allograft were associated with inferior survival. A summary of the Cox regression is shown in Table 2.

Table 2.

Results of univariable and multivariable Cox regression analyses regarding influence on survival, with hazard ratios (HR).

Variable	Univariable Cox regression		Multivariable Cox regression
	P value	HR (95% CI)	P value	HR (95% CI)
Recipient data
Age (years)	<0.001	1.036 (1.019–1.053)	0.007	1.027 (1.007–1.048)
BMI	0.905	1.002 (0.968–1.038)	Not included in model
Indication for OLT
Ethyl-tox/crypt. Cirrhosis (Ref.)	Reference		Reference
HBV-/HCV-related cirrhosis	0.152	0.682 (0.404–1.151)	0.127	0.653 (0.378–1.128)
HCC/NEC-metastases	0.011	0.576 (0.376–0.882)	0.005	0.533 (0.342–0.830)
PSC/PBC	<0.001	0.324 (0.188–0.559)	0.007	0.457 (0.258–0.809)
(Sub-)Acute liver failure	0.001	0.331 (0.170–0.644)	0.003	0.331 (0.158–0.690)
Others	<0.001	0.384 (0.227–0.650)	0.010	0.463 (0.259–0.829)
Laboratory MELD	0.615	1.004 (0.987–1.022)	Not included in model
Encephalopathy (yes)	0.318	1.196 (0.842–1.697)
Hemodialysis pre-OLT (yes)	0.040	1.609 (1.022–2.533)
Respirator treatment pre-OLT (yes)	0.084	1.719 (0.929–3.179)
Donor data
Age (years)	0.056	1.011 (1.000–1.023)
BMI	0.607	0.992 (0.963–1.023)
IDDM/NIDDM (Ref. none)	0.329	0.783 (0.479–1.280)
Insulin treatment (Ref. none)	0.358	1.944 (0.471–8.022)
ICU-stay (days)	0.085	1.031 (0.996–1.067)
AST (U/L)	0.737	1.000 (0.999–1.001)
Steatosis in graft (Ref. none)	<0.001	1.749 (1.278–2.393)	0.041	1.427 (1.000–2.007)
OLT
CIT (min)	0.189	1.001 (1.000–1.001)	Not included in model
Duration of surgery	0.121	1.002 (0.999–1.005)
Primary abdominal closure (yes)	0.002	1.732 (1.218–2.464)	0.050	1.475 (1.000–2.177)
Complications graded Dindo ≥3	<0.001	2.311 (1.505–3.549)	0.001	2.187 (1.380–3.465)
ICU stay (days)	<0.001	1.007 (1.003–1.010)	Not included in model
Hospital stay (days)	0.035	1.004 (1.000–1.007)

BMI – body mass index; AST – aspartate aminotransferase; OLT – orthotopic liver transplantation; MELD – model for end-stage liver disease; ICU – intensive care unit; CIT – cold ischemia time; HCC/NEC – hepatocellular carcinoma/neuroendocrine; PCS/PBC – primary sclerosing cholangitis/primary biliary cholangitis; IDDM – insulin-dependent diabetes mellitus; NIDDM – non–insulin-dependent diabetes mellitus.

Discussion

This study aimed to achieve a more comprehensive understanding of the effect of hepatic steatosis in liver allografts on long-term survival after OLT. The study highlights hepatic steatosis as an independent risk factor associated with poorer long-term survival, as demonstrated by Kaplan-Meier and multivariable Cox regression analyses conducted on a large cohort of more than 300 patients in a major German liver transplantation center. Furthermore, patients receiving fatty liver grafts (group B) exhibited significantly higher in-house mortality and rates of primary non-function than did recipients of non-steatotic grafts (group A). Therefore, even if the multivariable Cox regression analyses indicated only a less favorable long-term outcome, negative effects on short-term outcome might be presumed.

The elevated risk associated with steatotic grafts is likely mediated by substantial cellular damage evident through significantly higher levels of AST and ALT after OLT, reflecting hepatocellular injury [20,25]. In this cohort, macrovesicular steatosis of 20% or greater was observed in over 35% of biopsied grafts, with 25% exhibiting 30% or greater. Since not all pathology reports quantified steatosis, the true incidence may be underestimated. These results align with findings by Angele et al, who reported that liver grafts with moderate to severe steatosis exhibited a significant increase in transaminase levels during the first 2 days after surgery. Whereas, after 7 days, no differences in liver function were observed, compared with grafts with mild steatosis, and long-term survival remained unaffected [26]. Steatotic grafts are particularly susceptible to I/R injury, which increases postoperative risk.

Croome et al demonstrated that macrovesicular steatosis of at least 30% correlates with a higher incidence of post-reperfusion syndrome, which in turn is associated with a higher incidence of early graft dysfunction, reoperation, and acute kidney injury [27]. Similarly, McCormack et al demonstrated increased primary non-function and an increased incidence of acute renal failure in donor livers with severe steatosis (>60%) [28]. These findings are likely to contribute to the elevated in-hospital mortality observed in recipients of fatty liver grafts in this study.

Despite the general agreement between the present study and previous studies, discrepancies remain. Gao et al reported no significant short-term functional differences in grafts with moderate steatosis (30–60%) [29]. Furthermore studies focusing on microvesicular steatosis showed varying results with regard to the occurrence of postoperative complications, such as early graft dysfunction and primary non-function; however, they unanimously showed no difference in patient survival rates after transplantation [30,31]. These discrepancies may reflect heterogeneity in steatosis assessment, differences in macrovesicular vs microvesicular fat content, and variations in perioperative management across transplant centers and countries.

Hepatocellular and sinusoidal endothelial injury during organ procurement, ischemia, and reperfusion is primarily mediated by cytokines and accumulation of toxic metabolites [25]. Addressing these aspects is essential for improving outcomes following OLT of fatty liver allografts.

While static cold storage remains the predominant preservation method because of simplicity and cost-effectiveness [32], it fails to mitigate I/R injury, based on the absence of oxygen flow, which leads to anaerobic metabolism and the accumulation of toxic metabolites [33]. Reperfusion of the liver with warm, oxygenated blood at the time of transplantation then leads to the release of accumulated cytokines and chemokines, further amplifying I/R injury and increasing the risk of primary graft failure and dysfunction [34]. This effect is further aggravated by prolonged cold ischemia time [20,33]. Durations exceeding 4 hours are already associated with an increased risk of graft loss, longer hospitalization, and higher rates of primary non-function [35]. Lozanovski et al were also able to demonstrate a linear influence between the duration of cold ischemia time and the risk of graft loss within the first year, with the risk increasing by 3.4% with each additional hour of cold ischemia time [36]. Consequently, minimizing both the cold and warm ischemia times remains essential to optimize allograft outcomes, especially for organs with extended criteria, including fatty allografts [8].

One of the most promising instruments to optimize the assessment and possibly even the improvement of steatotic liver grafts could be the established technique of machine perfusion. Several studies have demonstrated the superiority of machine perfusion over static cold storage, especially in fatty livers [6,12,33,34]. The potential benefits are considerable, as this method expands the donor organ pool and reduces both the waitlist time and mortality [37]. Machine perfusion ensures a continuous supply of oxygen and nutrients, thereby limiting the initial release of mitochondrial reactive oxygen species, preventing ischemic injury, and potentially improving lipid metabolism and microcirculation [5,12,13,34]. During normothermic machine perfusion, Boteon et al demonstrated improved lipid metabolism and decreased lipid content in human livers, leading to functional recovery and reduced expression of reperfusion injury markers [38]. Furthermore, several studies have identified lactate clearance, pH stability, declining transaminase levels, and bile production as real-time markers for assessing cellular and biliary viability during perfusion [39–41]. Supporting the effectiveness of machine perfusion, Serifis et al reported a positive effect on cellular energy reserves, aiming to prevent I/R damage [34]. In addition, Schlegel et al showed that livers subjected to machine perfusion exhibit significantly reduced peak enzyme release, shorter hospital stay, and lower early graft dysfunction [42]. Taken together, these findings highlight machine perfusion as a promising and forward-looking strategy to enhance the safety of using steatotic grafts for liver transplantation.

However, the study has some limitations that reduce the strength of the evidence. These include the retrospective, single-center design and, most importantly, the nonstandardized evaluation of fatty livers related to retrospective data assessment and interobserver variability among donor surgeons, radiologists, and pathologists across participating donor hospitals in Europe.

Furthermore, the influence of postoperative management may have been different over the 11-year study period. Despite the limitations, the data provide profound evidence that fatty liver allografts are associated with a negative effect on short- and long-term survival after OLT. Future research should aim to standardize histological and radiological steatosis grading, incorporate multicenter prospective designs, and evaluate machine perfusion-based optimization protocols.

Conclusions

In conclusion, our findings indicate less favorable outcomes and increased cellular injury following fatty liver transplantation. This highlights the urgency for research aimed at improving hepatic synthesis and reducing I/R injury. Careful donor selection, minimization of ischemia times, and integration of perfusion technologies are key strategies for improving outcomes when using fatty liver grafts. Further randomized prospective studies are needed to demonstrate the beneficial effects of machine perfusion and potentially provide a basis for broad recommendations regarding its use.