Mitigating Cold Ischemic Injury: HTK, UW and IGL-2 Solution's Role in Enhancing Antioxidant Defence and Reducing Inflammation in Steatotic Livers.

Liver transplantation remains the only definitive treatment for end-stage liver diseases. However, the increasing prevalence of fatty liver disease among potential donors exacerbates the shortage of suitable organs. This study evaluates the efficacy of the preservation solution Institut Georges Lopez-2 (IGL-2) compared to Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in mitigating ischemia-reperfusion injury (IRI) in steatotic livers. Using Zucker Obese rat livers, we assessed the impact of 24-h static cold storage (SCS) with each solution on transaminase release, glutathione redox balance, antioxidant enzyme activity, lipoperoxidation, and inflammation markers. IGL-2 and UW solutions demonstrated reduced transaminase and lactate levels compared to HTK, indicating better preservation of liver integrity. IGL-2 maintained a higher reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, suggesting more effective management of oxidative stress. Antioxidant enzyme activities catalase, superoxide dismutase, and glutathione peroxidase (CAT, SOD, GPX) were higher in IGL-2 preserved livers, contributing to decreased oxidative damage. Lipid peroxidation markers and inflammatory markers were lower in IGL-2 than in HTK, indicating reduced oxidative stress and inflammation. Additionally, improved mitochondrial function was observed in the IGL-2 group, correlating with reduced reactive oxygen species (ROS) production and lipid peroxidation. These findings suggest that IGL-2 offers superior preservation of liver viability, reduces oxidative stress, and minimizes inflammation compared to HTK and UW solutions. By maintaining a higher ratio of reduced glutathione and antioxidant enzyme activity, IGL-2 effectively mitigates the harmful effects of ischemia-reperfusion injury. The reduced lipid peroxidation and inflammation in the IGL-2 group further underscore its potential in improving liver transplant outcomes. These results highlight the importance of optimizing preservation solutions to enhance the viability and functionality of donor organs, potentially expanding the donor pool and improving the success rates of liver transplantation. Future research should focus on refining preservation techniques and exploring additional protective agents to further improve organ preservation and transplant outcomes.

Women Are Also Disadvantaged in Accessing Transplant Outside the United States: Analysis of the Spanish Liver Transplantation Registry.

Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000-2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7 years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5 days, p < 0.001). Recently, women's risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource.

Optimized results of the liver partition program for split-liver transplantation.

INTRODUCTION: Split liver transplantation is a procedure performed throughout Europe. In 2018 in Catalonia, the distribution of donors was redefined, being potential candidates for SPLIT all those under 35-years and it was made flexible the adult selection for the right graft. The study aim is to evaluate the effect of this modifications on the use of Split donors on the adult/pediatric waiting lists, as well as to evaluate the post-transplant results of adults who received a Split donor. METHODS: Observational and retrospective study; 2 data collection periods "PRE" (2013-2017) and "POST" (2018-2021). The adults recipients results were analyzed by a propensity score matching. RESULTS: In the first period 3 donors were registered and 3 pediatric patients and 2 adults recieved a transplant. In the POST period, 24 donations with liver bipartition were made, performing the transplant in 19 adults and 24 childrens. When comparing the adults waiting lists, a significant decrease was evidenced, both for adults (p = 0,0001) and on the children's waiting list (p = 0,0004), and up to 3 times there were no recipients on the pediatric waiting list. No significant differences between hospital morbidity or mortality or overall survival were observed in the group of adult recipients of Split grafts. CONCLUSIONS: The flexibility in the selection of the adult recipient and the new distribution of donors makes possible to increase the bipartition rate, reducing the pediatric waiting list without worsening the adults results transplant recipients or their permanence on the waiting list.

Normothermic perfusion and outcomes after liver transplantation.

Ischemia has been a persistent and largely unavoidable element in solid organ transplantation, contributing to graft deterioration and adverse post-transplant outcomes. In liver transplantation, where available organs arise with greater frequency from marginal donors (i.e., ones that are older, obese, and/or declared dead following cardiac arrest through the donation after circulatory death process), there is increasing interest using dynamic perfusion strategies to limit, assess, and even reverse the adverse effects of ischemia in these grafts. Normothermic perfusion, in particular, is used to restore the flow of oxygen and other metabolic substrates at physiological temperatures. It may be used in liver transplantation both in situ following cardiac arrest in donation after circulatory death donors or during part or all of the ex situ preservation phase. This review article addresses issues relevant to use of normothermic perfusion strategies in liver transplantation, including technical and logistical aspects associated with establishing and maintaining normothermic perfusion in its different forms and clinical outcomes that have been reported to date.

Pretransplant lymphocyte count predicts the incidence of infection during the first two years after liver transplantation.

Patients with end-stage liver disease (ESLD) show a low absolute number of peripheral blood lymphocyte subpopulations (PBLSs). We investigated if the baseline PBLS could categorize orthotopic liver transplantation (OLT) recipients into groups at high or low risk for infection after transplantation. PBLSs were prospectively studied in 63 consecutive patients (42 males; mean age +/- standard deviation: 53.5 +/- 10.3 years) with ESLD prior to OLT. Thirty-five patients (55.6%) developed a total of 79 infectious episodes during the first 2 years post-OLT. The median total lymphocyte count and PBLS levels [CD3+ T cells, CD4+ T cells, memory (CD45RO+) CD4+ T cells, T cell receptor alphabeta+ and gammadelta+ subsets, and CD19+ B cells] at baseline were significantly lower in patients with an infection compared with those without one (P < 0.05). There was a significant correlation between the risk of development of a post-OLT infection and a baseline total lymphocyte count < 1.00 x 10(3)/microL (P = 0.001), a baseline CD3+ T cell count < 0.75 x 10(3)/microL (P = 0.009), and a baseline CD4+ T cell count < 0.5 x 10(3)/microL (P = 0.008). In the multivariate analysis, this association between the baseline total lymphocyte level and infection remained significant (odds ratio: 10.1; 95% confidence interval: 1.9-39.5). In conclusion, the pre-OLT total lymphocyte count identifies a subset of patients at high risk for infection. PBLS monitoring prior to OLT may offer an opportunity for surveillance, tapering of immunosuppression, and preemptive therapy.