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.
Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal albumin dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP) analysis. Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior standard medical therapy (SMT). Patients were randomized to receive SMT with ECAD or without (control). ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer (MW cutoff < 60 kd) against 15% albumin. Albumin-bound molecules transfer to dialysate albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer. ECAD was associated with improved 30-day survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P <.05). Plasma bile acids and bilirubin decreased on average by 43% and 29%, respectively, in the ECAD group after 1 week of treatment, but not in the control group. Renal dysfunction and hepatic encephalopathy improved in the ECAD group, but worsened significantly in the control group. ECAD was safe, with adverse events being rare and identical in both groups. In conclusion, ECAD appears to be effective and safe for the short-term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation.
This is the first analysis of the ALPPS registry showing that ALPPS has increased perioperative morbidity and mortality in older patients but better outcomes in patients with CRLM.
Since the introduction of adult-to-adult living donor liver transplantation using the right lobe of the liver, biliary problems have led the list of complications resulting in postoperative morbidity. We report our experience with the first 30 living donor liver transplantations performed in our institution from August 1998 to January 2000. Patients were 21 men and 9 women, with a mean age 45 ؎ 16 years. Mean recipient weight was 65.1 ؎ 17.9 kg, mean graft weight was 877 ؎ 146 g, and the mean graft-recipient weight ratio was 1.5 ؎ 0.6. Patient and graft survival rates were 83.3% and 80%, respectively. Biliary anastomosis was either an end-to-end hepaticocholedochostomy with a T-drain or hepaticojejunostomy. Mean follow-up was 217.4 ؎ 149.8 days. The overall complication rate was 26.6% (8 of 30 procedures) and was directly correlated to the type of anastomosis and number of bile ducts. Surgical revision was necessary in all cases. Biliary complications were not the primary cause of graft loss. Adult living donor liver transplantation using the right lobe is a successful procedure, with graft and patient survival similar to those in cadaver full-organ transplantation. Postoperative morbidity, mainly caused by biliary leak, was directly related to the number of ducts and type of anastomosis. With increasing experience, we have better defined our plane of transection on the hilar plate, with the goal of obtaining only 1 biliary duct for the anastomosis. We also improved our parenchymal transection technique, which resulted in a decreased incidence of leak at the cut-surface area. (Liver Transpl 2000;6:710-714.)
In our transplant program, living donor liver transplantation has become a standard option in the adult patient population. The critical issue of this procedure is donor morbidity. Technical improvements in the harvesting and implantation of right grafts can also offer hope to patients with challenging forms of end-stage liver disease or malignant liver tumors.
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