Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.
Liver synthetic and metabolic function can only be optimised by the growth of cells within a supportive liver matrix. This can be achieved by the utilisation of decellularised human liver tissue. Here we demonstrate complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture. Decellularized human liver cubic scaffolds were repopulated for up to 21 days using human cell lines hepatic stellate cells (LX2), hepatocellular carcinoma (Sk-Hep-1) and hepatoblastoma (HepG2), with excellent viability, motility and proliferation and remodelling of the extracellular matrix. Biocompatibility was demonstrated by either omental or subcutaneous xenotransplantation of liver scaffold cubes (5 × 5 × 5 mm) into immune competent mice resulting in absent foreign body responses. We demonstrate decellularization of human liver and repopulation with derived human liver cells. This is a key advance in bioartificial liver development.Deaths from liver disease are increasing worldwide. According to the World Health Organisation, the total deaths caused by cirrhosis and liver cancer have increased by 50 million/year since 1990 1 . In the UK, the number of deaths from cirrhosis in those < 65 years have increased ~6 fold in the last 30 years 2 . At present, liver transplantation is the only successful treatment for patients with end stage liver disease. However, 20% of patients die on the waiting list due to a shortage of organ donors 3 . To expand the supply of livers available for transplantation, transplant surgeons and physicians have explored several new approaches including split liver transplants, living-related partial donor procedures 4 and the increasing use of "marginal" organs such as older donors, steatotic livers, non-heart-beating donors, donors with viral hepatitis, and donors with non-metastatic malignancy 5 . Despite these medical and surgical developments, it is unlikely that the availability of good liver grafts will ever be sufficient to meet the increasing demand of patients with end stage liver disease.Alternatives to liver transplantation such as liver support systems, including bioartificial livers, and hepatocyte transplantation have been extensively explored but none adopted in clinical practice [6][7][8][9][10][11] .In the UK, over 40% of the livers offered for transplantation are declined because of prolonged ischemic time or co-morbidities judged beyond marginal criteria 12 . This provides us with a major opportunity to explore alternative uses of human livers found to be unsuitable for transplantation following organ retrieval. In particular, while cellular viability is easily compromised, extracellular matrix (ECM) is better maintained in the discarded livers and it may be used as scaffold in which to grow normal human liver cells and recreate functional human liver tissue in vitro. Such cells could be obtained from
Liver failure is a dreaded and often fatal complication that sometimes follows a partial hepatic resection. This article reviews the definition, incidence, pathogenesis, risk factors, risk assessment, prevention, clinical features and treatment of post‐resectional liver failure (PLF). A systematic, computerized search was performed using key words related to ‘partial hepatic resection’ and ‘liver failure’ to review most relevant literature about PLF published in the last 20 years. The reported incidence of PLF ranges between 0.7 and 9.1%. An inadequate quantity or quality of residual liver mass are key events in its pathogenesis. Major risk factors are the presence of comorbid conditions, pre‐existent liver disease and small remnant liver volume (RLV). It is essential to identify these risk factors during the pre‐operative assessment that includes evaluation of liver volume, anatomy and function. Preventive measures should be applied whenever possible as curative treatment options for PLF are limited. These preventive measures intend to increase RLV and protect remnant liver function. Management principles focus on support of end‐organ and liver function. Further research is needed to elucidate the exact pathogenesis of PLF and to develop and validate adequate treatment options.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.