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.

Surgical Treatment of Persistent Pseudomonas aeruginosa Bacteraemia After n-Butyl-2-cyanoacrylate for Gastric Bleeding Varices.

n-Butyl-2-cyanoacrylate (NCBA) is an effective therapeutic option for bleeding gastric varices but can sometimes be associated with adverse effects. Persistent bacteraemia is an unusual complication with a high mortality rate. We report the case of a 34-year-old man with history of cirrhosis due to Wilson's disease and severe portal hypertension who was hospitalized as a result of upper gastrointestinal bleeding secondary to fundic varices that were treated with NCBA. Eight weeks after the bleeding episode he was readmitted with a 14-day history of fever and chills. Pseudomonas aeruginosa was isolated from blood cultures. He presented with persistent P. aeruginosa bacteraemia despite correct antibiotic treatment. A PET-CT scan was performed to rule out infection source, and inflammatory changes at the NCBA site plug were found. A presumptive diagnosis of NCBA plug infection was considered. The case was evaluated by multidisciplinary board and indicated liver transplantation as treatment. However, the patient's bacteraemia persisted and therefore a vertical gastrectomy to remove the NCBA plug was performed. P. aeruginosa was also isolated from the plug. The patient was discharged with ceftazidime plus ciprofloxacin to complete 6 weeks after surgery and he remained asymptomatic. Any foreign material such as NCBA is susceptible to being infected and should be considered in patients with persistent breakthrough bloodstream infections. The individualized treatment is recommended in this complex scenario.

Focusing on Ischemic Reperfusion Injury in the New Era of Dynamic Machine Perfusion in Liver Transplantation.

Liver transplantation is the most effective treatment for end-stage liver disease. Transplant indications have been progressively increasing, with a huge discrepancy between the supply and demand of optimal organs. In this context, the use of extended criteria donor grafts has gained importance, even though these grafts are more susceptible to ischemic reperfusion injury (IRI). Hepatic IRI is an inherent and inevitable consequence of all liver transplants; it involves ischemia-mediated cellular damage exacerbated upon reperfusion and its severity directly affects graft function and post-transplant complications. Strategies for organ preservation have been constantly improving since they first emerged. The current gold standard for preservation is perfusion solutions and static cold storage. However, novel approaches that allow extended preservation times, organ evaluation, and their treatment, which could increase the number of viable organs for transplantation, are currently under investigation. This review discusses the mechanisms associated with IRI, describes existing strategies for liver preservation, and emphasizes novel developments and challenges for effective organ preservation and optimization.