Dynamically preserving organs has produced several benefits, including improved liver health, enhanced graft longevity, reduced hepatic injury, and diminished post-transplant challenges. Accordingly, organ perfusion approaches are currently being implemented clinically in numerous countries. Despite their successful transplantation, a segment of livers fail to meet the viability standards necessary for procedures, even with the application of cutting-edge perfusion methods. Consequently, the need for devices to further maximize machine liver perfusion is evident; an encouraging prospect is to maintain machine liver perfusion for several days, encompassing ex situ treatment protocols on the perfused liver. To modulate repair mechanisms and encourage regeneration during extended liver perfusion, various therapeutic modalities may be applied, including the administration of stem cells, senolytics, or compounds targeting mitochondria or downstream signaling cascades. Furthermore, contemporary perfusion apparatus is crafted to facilitate the application of diverse liver bioengineering methods, enabling the development of supportive scaffolds or their subsequent re-cellularization. Modification of animal livers, either through whole-liver or cellular gene modulation, serves diverse purposes including xenotransplantation, direct treatment of injured organs, or replenishment of such scaffolds with autologous cells. Concerning current strategies to improve the quality of donor livers, this review first considers them and secondly delves into bioengineering techniques for designing optimized organs during machine perfusion. Current perfusion strategies, along with their inherent benefits and challenges, are explored.
Circulatory death donation (DCD) liver grafts are utilized in several countries to mitigate organ scarcity. Yet, these DCD grafts are linked to a heightened possibility of postoperative complications and even complete loss of the transplanted liver. selleck chemicals llc The increased risk of complications is hypothesized to be directly related to the duration of functional donor warm ischemia. Endosymbiotic bacteria Outcomes have been enhanced due to the strict donor selection criteria and the use of in situ and ex situ organ perfusion technologies. Importantly, the greater deployment of novel organ perfusion strategies has opened up the possibility of improving the condition of marginal DCD liver allografts. Furthermore, these technologies facilitate the pre-implantation evaluation of liver function, yielding valuable data that allows for a more precise matching of grafts and recipients. This review initially details the diverse interpretations of functional warm donor ischaemia time and its influence on post-DCD liver transplantation outcomes, highlighting the thresholds for graft acceptance. Subsequently, strategies for organ perfusion, including normothermic regional perfusion, hypothermic oxygenated perfusion, and normothermic machine perfusion, will be examined. Descriptions of transplant outcomes from clinical studies for each technique, including discussions on possible protective mechanisms and graft selection's functional criteria, are presented. In conclusion, we examine multimodal preservation protocols, which encompass the use of more than one perfusion technique, and discuss potential future paths in this domain.
The management of patients suffering from end-stage diseases of the kidneys, liver, heart, and lungs has incorporated solid organ transplantation as a fundamental element. Despite the common practice of performing procedures in isolation, the combination of liver transplantation with either a kidney or heart transplant is now a viable option. With the growing number of adult patients with congenital heart disease and cardiac cirrhosis, particularly those who have had the Fontan procedure, the need for multi-organ (heart-liver) transplantation will likely be raised before liver transplant teams. Patients afflicted with polycystic kidneys and livers may be candidates for a combined approach using multi-organ transplantation. In this review, the applicability and results of simultaneous liver-kidney transplants for polycystic liver-kidney disease are discussed. This is followed by a discussion of the necessary criteria, timing, and procedural considerations for combined heart-liver transplants. In addition, we synthesize the proof for, and the likely mechanisms governing, the immunoprotective effect of liver allografts on the simultaneously transplanted organs.
Living donor liver transplantation (LDLT) provides a substitute approach to the problem of high waiting list mortality rates and facilitates the expansion of the donor pool. A significant increase in the number of reports on the utilization of LT, and specifically LDLT, for familial hereditary liver diseases has occurred during recent decades. A crucial assessment of both slight indications and contraindications is necessary for living donors in pediatric parental liver transplantation (LDLT). Heterozygous donor status has proven largely devoid of mortality or morbidity due to recurrent metabolic diseases, though specific instances such as ornithine transcarbamylase deficiency, protein C deficiency, hypercholesterolemia, protoporphyria, and Alagille syndrome are exceptions. Donor human leukocyte antigen homozygosity is also a noteworthy risk. kidney biopsy Performing preoperative genetic assays for potential heterozygous carriers is not consistently necessary; nonetheless, genetic and enzymatic tests will henceforth be integral components of parental donor selection criteria in these situations.
Cancers commonly disseminate to the liver, particularly those with their origins in the gastrointestinal tract. While less commonly employed, liver transplantation for neuroendocrine and colorectal liver metastases stands as a promising, yet at times controversial, treatment option. Individuals with neuroendocrine liver metastases who undergo transplantation with carefully selected patients often experience excellent long-term results, but the optimal utilization of transplantation in individuals who are eligible for hepatectomy, the role of neoadjuvant/adjuvant treatments in mitigating recurrence, and the best time for the procedure remain to be determined. Prospective research on liver transplantation for unresectable colorectal liver metastases indicated a 5-year overall survival rate of 60%, thereby rekindling interest following a period of initially bleak outcomes. Subsequent to this, comprehensive investigations have been undertaken, and ongoing prospective trials are evaluating the comparative advantages of liver transplantation relative to palliative chemotherapy. This review offers a critical evaluation of the current state of knowledge regarding liver transplantation for neuroendocrine and colorectal liver metastases, and emphasizes the importance of further research to address the inadequacies in the present evidence.
For individuals with severe acute alcohol-related hepatitis unresponsive to medical management, liver transplantation (LT) constitutes the sole effective therapeutic intervention. Strict adherence to pre-defined protocols is associated with an improvement in survival and a manageable rate of post-transplant alcohol use. Liver transplantation (LT) access for patients with severe alcohol-related hepatitis remains highly variable. This variability stems largely from the overemphasis on pre-transplant sobriety durations and the persistent stigma associated with alcohol-related liver disease, ultimately contributing to disparities in access to potentially life-saving procedures and resulting in adverse health outcomes. Thus, there is a rising necessity for prospective, multi-centered research studies that focus on the pre-transplant evaluation of candidates and on the development of enhanced post-transplant interventions for alcohol use disorder following liver transplantation.
This discussion evaluates the suitability of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis for liver transplantation (LT) procedures. The justification for LT in this situation rests on the assumption that, after a successful downstaging treatment, LT results in a considerably greater benefit concerning survival compared to the other current choice, which is palliative systemic therapy. Arguments against LT in this case heavily rely on the limitations of the evidence, including flawed study designs, diverse patient profiles, and inconsistent approaches to downstaging. Though LT offers superior outcomes for patients with portal vein tumour thrombosis, a counter-point emphasizes that anticipated survival in these patients remains below accepted thresholds for LT, and lower than those realized by transplant recipients beyond the Milan criteria. The available evidence presently discourages consensus guidelines from recommending this method; however, it's hoped that the accumulation of higher-quality data and the implementation of standardized downstaging protocols will lead to wider utilization of LT, including in this population with critical unmet clinical needs.
The authors of this debate investigate whether patients with acute-on-chronic liver failure of grade 3 (ACLF-3) should receive higher priority in liver transplantation procedures, utilizing a case study of a 62-year-old male with decompensated alcohol-related cirrhosis, marked by recurrent ascites and hepatic encephalopathy, and co-occurring metabolic conditions including type 2 diabetes mellitus, arterial hypertension, and a BMI of 31 kg/m2. The patient, following a liver transplantation (LT) assessment, was transferred to the intensive care unit, where mechanical ventilation was initiated due to neurological failure. An inspired oxygen fraction (FiO2) of 0.3 resulted in a blood oxygen saturation (SpO2) of 98%, and norepinephrine therapy was commenced at 0.62 g/kg/min. Following his cirrhosis diagnosis a year prior, he committed himself to abstinence. Admission lab results demonstrated a leukocyte count of 121 G/L, an INR of 21, a creatinine level of 24 mg/dL, sodium of 133 mmol/L, total bilirubin of 7 mg/dL, lactate of 55 mmol/L, a calculated MELD-Na score of 31, and a CLIF-C ACLF score of 67.