Background

Liver transplantation (LTx) remains the only curative treatment for end-stage liver disease, yet the persistent shortage of donor organs continues to limit its availability. Normothermic machine perfusion (NMP) has emerged as a promising technique to improve the assessment and preservation of marginal livers, with the potential to expand the donor pool. However, despite the use of NMP, a considerable proportion of livers are ultimately deemed unsuitable for transplantation. Understanding the underlying reasons for graft discard after NMP is crucial to refine selection criteria, improve perfusion strategies and enhance clinical outcomes.

Methods

A retrospective analysis was performed using data from our institutional liver transplant database. From all donor livers subjected to NMP since the implementation of NMP in our centre in 2018, we identified those ultimately not transplanted. For these grafts, donor characteristics, perfusion parameters, histological findings and documented reasons for discard were evaluated. In addition, we determined the proportion of discarded livers subsequently utilized for scientific research purposes.

Results

Between 02/2018 and 01/2025, 97 liver allografts were defined as not transplantable after NMP. Mean donor age was 57.20 +/- 15.61 years, median donor risk index was 1.97. 39.17% of livers stemmed from non-heartbeating donors (DCD), 94.84% of donors were defined as extended criteria and 27.83% of livers were rescue or extended allocation offers. 60 livers met established discard criteria: donor malignancy (n = 4), fibrosis II and steatohepatitis of the liver in frozen section (n = 25), macrovesicular steatosis of 40% or more (n = 16) or no sufficient lactate clearance within 6 hours of perfusion (n = 33). Dysfunction of the NMP-device and a graft that could not be re-allocated occurred in one case, respectively. 35 grafts did not meet obligatory discard criteria, but rather accumulated multiple relative criteria (elevated transaminase and LDH levels, no bile production or a low bile pH, mild steatosis). 30 livers (30.92%) were used for further experimental studies after being declined for transplantation.

Conclusion

Though expanding the donor pool, a substantial proportion of livers is deemed untransplantable even after NMP. The reasons for discard proved to be diverse and multifactorial with histological findings and failure to meet functional perfusion criteria representing the most common reasons. Systematic evaluation of discard reasons may help refine selection algorithms to ameliorate selection in more marginal organs. Finally, the utilization of declined organs offers significant scientific value, which is currently not fully exploited, due to the lack of an appropriate legal framework.

BACKGROUND

Access to deceased donor liver transplantation (DDLT) is shaped by a complex interplay of demographic, clinical, and system-level factors. Normothermic liver machine perfusion (NLMP) has improved organ utilization, but its effect on candidate-level access to transplantation remains unclear. Herein, we aim to investigate whether the implementation of a clinical NLMP program improves access to DDLT.

METHODS

This retrospective cohort study included all adult (≥ 18 years) liver transplant (LT) candidates wait-listed for DDLT between February 2012 and January 2024 at the Medical University of Innsbruck. The exposure of interest was listing in the pre-NLMP era versus the NLMP era, with clinical NLMP implemented in February 2018. Multivariable Cox proportional hazards regression was performed to identify independent predictors of receiving a DDLT. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) are reported. Independent predictors of receiving a DDLT were identified using multivariable Cox proportional hazards regression, reporting adjusted hazard ratios (aHR) with 95% confidence intervals (CI).

RESULTS

A total of 870 patients were waitlisted during the study period, including 219 listed as female (25,17%) and 651 as male (74,83%). Female sex was not significantly associated with DDLT access (aHR = 0.89, 95% CI: 0.72–1.09; p = 0.24), despite significance in univariable analysis. However, body size (aHR = 1.01 per cm, 95% CI: 1.00–1.02; p = 0.028) was independently associated with higher transplant probability. Clinical urgency remained the strongest predictor: high urgency (HU) status (aHR = 8.05, 95% CI: 5.58–11.60; p < 0.001), higher laboratory MELD score (aHR = 1.03 per point, 95% CI: 1.02–1.04; p < 0.001), and standardized exception MELD (SE-MELD) points (aHR = 1.51, 95% CI: 1.18–1.94; p < 0.001) all significantly improved access to DDLT. Additionally, listing during the NLMP era was retained in the final multivariable model as an independent predictor associated with higher probability of receiving a DDLT (aHR = 1.24, 95% CI: 1.07–1.44; p = 0.005).

CONCLUSIONS

In this large, contemporary cohort of DDLT candidates, both biological and system-level factors significantly influenced DDLT access. Clinical urgency markers such as HU status, MELD score, and SE-MELD were strong predictors, underscoring the prioritization framework of current allocation policies. The association between NLMP era listing and improved transplant access highlights the potential impact of evolving organ preservation strategies on waitlist outcomes.

BACKGROUND

The global shortage of donor organs emphasizes the need to optimize not only transplantation but also the full spectrum of organ use, including recovery for research and other scientific purposes. Eurotransplant (ET), a collaborative network of eight European countries, and the United States (US), operating under the Organ Procurement and Transplantation Network (OPTN), represent two of the most comprehensive organ-sharing systems worldwide. Comparing their utilization metrics over a decade provides insight into differences in donor reporting, allocation efficiency, and the extent to which each system contributes to research potential. Organs that cannot be transplanted represent a valuable resource for advancing transplantation science, immunology, and regenerative medicine.

METHODS

We conducted a retrospective analysis using ET Annual Reports and the US OPTN and Scientific Registry of Transplant Recipients from 2014–2023. Outcomes included total reported organs, transplanted organs, nontransplanted organs, and organs used for research or other purposes. Data were normalized per million population (PMP) for direct comparison using Eurostat and US Census estimates to enable direct comparison between regions and over time. Descriptive statistics were calculated, and linear regression analyses were performed to evaluate temporal trends. Statistical significance was defined as p < 0.05.

RESULTS

ET reported a mean of 10,026 organs annually (74.2 ± 3.7 PMP), compared with 70,910 in the US (215.7 ± 43.0 PMP). Transplanted organs averaged 6,802 (50.3 ± 2.9 PMP) in ET versus 31,941 (97.3 ± 14.1 PMP) in the US, corresponding to 67.8 % vs 45.0 % of reported organs. Total nontransplanted organs averaged 3,224 (23.9 ± 1.9 PMP, 32.2 %) in ET and 38,969 (118.5 ± 29.1 PMP, 55.0 %) in the US. Within the US nontransplanted group, a mean of 4,944 organs (15.0 ± 4.6 PMP, 12.7 %) were recovered for research and 818 (2.49 ± 0.73 PMP, 2.1 %) for other purposes, categories not reported by ET. Linear regression showed significant annual increases in all categories in the US (p < 0.001). In ET, no significant temporal change was observed in reported or nontransplanted organs, whereas transplanted organs showed a significant decline per year (p = 0.024).

CONCLUSIONS

When adjusted for population, the US reports nearly three times more organs but transplants a smaller proportion compared with ET. ET’s higher utilization rate likely reflects selective reporting of higher-quality donors, whereas the US includes a broader donor pool and diverts many nontransplantable organs into research pathways, ensuring scientific benefit. These differences are also shaped by the underlying reporting and donation systems. Together, these findings suggest that ET could evolve toward a more comprehensive system by broadening donor reporting criteria and introducing a structured framework for organ use in research, thereby improving transparency and maximizing both clinical and scientific impact.

Background:

Micronutrient deficiencies are frequent in obese and post-bariatric patients, and a poor folate status has been linked to adverse hepatic outcomes. While metabolic-associated steatotic liver disease/-steatohepatitis (MASLD/MASH) improves in most bariatric patients, around 20% remain “non-responders” with ongoing fibrosis despite weight loss. A recent NHANES study showed that high serum folate was associated with a markedly lower risk of advanced fibrosis, suggesting a potential protective role. The mechanisms, however, remain poorly defined.

Objective:

We hypothesized that folate deficiency contributes to liver fibrosis progression, particularly in the context of macronutrient overload, and aimed to investigate this in a novel MAFLD/MASH animal model.

Methods:

Male Sprague-Dawley rats (n=6/group) received either a high-fat/high-fructose diet (HFFD) with standard folate content (10 mg FA/kg chow) or a folate-depleted HFFD (0.02 mg FA/kg). To further reduce bioavailable folate, half of each group received fortnightly low-dose Methotrexate (Mtx, 0.5 mg/kg), a folate antagonist known to induce liver injury. After 8 weeks, we performed histological analysis, flow cytometry of hepatic stellate cells (HSC, CD45- CD90-) and fibroblast precursors (CD45- CD90+), and characterization of hepatic immune subsets. Intestinal barrier function was assessed by transepithelial resistance (TEER) and permeability assays.

Results:

Preliminary data indicate that adequate dietary folate is associated with attenuated MAFLD activity. At a single-cell level, folate sufficiency reduced hepatic inflammation, HSC activation (αSMA, desmin protein expression), and antigen-presenting cell abundance. The absence of folate further aggravated inflammatory responses under HFFD compared to standard chow. While Mtx did not directly enhance fibrosis markers, it was associated with immune-modulatory effects and increased intestinal permeability, especially in the folate-depleted setting.

Conclusion:

Our findings suggest that the folate status might modulate key pathways in MAFLD/MASH progression. Adequate folate intake appears to dampen hepatic inflammation, reduce stellate cell activation, and stabilize immune homeostasis, whereas folate deficiency might increase vulnerability to fibrosis, particularly when combined with gut barrier dysfunction. These results highlight folate as a potentially modifiable factor in preventing progression of liver fibrosis in at-risk populations, warranting further mechanistic and translational studies.

Background

Obesity and metabolic associated fatty liver disease (MASLD) has been linked to increased intestinal permeability (IP) or "leaky gut". Metabolic-bariatric surgery (MBS) is an effective treatment for obesity and related metabolic disorders, but its impact on IP remains unclear.

Objectives

This study investigates the relationship between intestinal permeability and liver fibrosis in an obese MASH rat model following one-anastomosis gastric bypass (OAGB) compared to sham surgery.

Methods

Male Sprague Dawley rats (n=16) were fed a high-fat, high-cholesterol, high-fructose, and low-folate diet, combined with methotrexate injections (0.5 mg/kg, i.p., after 2, 4 and 6 weeks) to induce fibrotic steatohepatitis (MASH) and increased IP. Liver and intestine were evaluated after eight weeks in a group of 5 animals, further groups underwent either OAGB (n=6) or sham surgery (n=5), followed by another eight weeks on the same diet. Thereafter, MASLD and IP were assessed histologically in different small intestinal sections. Ussing chamber experiments evaluated tissue resistance and permeability.

Results

After 8 weeks rats developed fibrotic MASH with increased IP. OAGB significantly reduced body weight and fasting blood glucose compared to sham surgery. Rats with MASH showed lower gut tissue resistance compared to MAFL; those with fibrosis exhibited higher permeability than those without fibrosis. Ileum tissue resistance was significantly higher in OAGB than in sham rats and pre surgical rats. A negative correlation was found between tissue resistance in the jejunum and intestinal lamina propria mononuclear cells.

Conclusions

Bariatric surgery improved intestinal permeability and increased gut resistance in this rodent model. Higher IP was associated with MASH and fibrosis, suggesting that intestinal permeability may play a critical role in MASLD improvement following MBS.