Use of marginal donors

Garcia, Christian Evangelista; Bramhall, Simon R.; Mirza, Darius F.

doi:10.1097/00075200-200006000-00002

Cited by 12 publications

(7 citation statements)

References 50 publications

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“…14,16,17 In our series, 82.5% fulfilled the simple criteria and only 17.5% would have required referral to an assessment committee. The mortality of patients with PBC while on the waiting list has recently been analyzed in Europe.…”

Section: Resultsmentioning

confidence: 69%

Transplantation for Primary Biliary Cirrhosis: Retrospective Analysis of 400 Patients in A Single Center

et al. 2001

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Orthotopic liver transplantation (OLT) is an effective treatment for patients with advanced primary biliary cirrhosis (PBC). We have conducted a retrospective analysis of 400 consecutive patients transplanted for PBC between 1983 and 1999. Mean follow-up was 56 months. The proportion of patients grafted for PBC fell progressively, from 35% in 1990 (n ‫؍‬ 80) to 21% in 1999 (n ‫؍‬ 111); comparison of patients grafted in the 2 decades showed that the median age increased from 53 to 56 years and the median serum bilirubin at transplantation fell from 270 mol/L to 132 mol/L. The overall actuarial patient and graft survival at 1, 5, and 10 years is 83%, 78%, and 67% and 82%, 75%, and 61%, respectively. The net gain in 5-year survival compared with predicted survival in the absence of transplantation fell from 37% (range, 82%-90%) to 16% (range, 91%-99%). Multiple organ failure (16.1%) and sepsis (9.6%) were the major causes of early deaths (<6 months). Recurrent PBC, diagnosed on allograft histology, was found in 68 (17%) patients, at a mean time of 36 months. We were unable to identify any pretransplantation donor or recipient factor, which identified those patients at risk of recurrence, although recurrence was much earlier and more frequently seen in patients receiving tacrolimus (P ‫؍‬ .04). PBC remains a good indication for liver transplantation, with excellent survival rates. The age at transplantation increased although patients tended to be grafted earlier. Survival rates have increased although there is a reduction in the survival benefit. Recurrence may be common, but does not seem to affect medium-term graft survival. (HEPATOLOGY 2001;33:22-27.)Orthotopic liver transplantation (OLT) in humans was first successfully reported by Starzl in 1968 1 ; in the early years, few patients were transplanted and survival rates were poor. With increasing experience; better selection; improved surgical, anesthetic, and microbiological techniques; and the introduction of potent immunosuppressive agents, results have improved considerably. As results have improved, patients have been offered transplantation when they are less ill and more likely to withstand the stresses of the procedure and the postoperative period.Primary biliary cirrhosis (PBC) has been one of the most common indications for liver transplantation in adults. 2 Although the pathogenesis remains uncertain and medical therapy, at best, only slows progression of the disease, the natural history is well understood and there are several prognostic models that have been developed to predict not only survival in the absence of transplantation but also survival after transplantation. 3,4 The indications for transplantation are relatively well defined: either a poor quality of life, usually because of intractable lethargy or pruritus, or an anticipated length of life less than 1 year. 5

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Section: Resultsmentioning

confidence: 69%

Transplantation for Primary Biliary Cirrhosis: Retrospective Analysis of 400 Patients in A Single Center

et al. 2001

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“…This growing disparity in supply and demand has catalyzed the use of marginal grafts which are either steatotic or cholestatic. 1,2 Marginal livers have an increased susceptibility to cold and warm ischemia reperfusion (I/R) injury resulting in poor graft outcomes. 3–5 Cholestasis is a major risk factor for oxidative stress and complications of I/R injury.…”

Section: Introductionmentioning

confidence: 99%

Cyclopamine Attenuates Acute Warm Ischemia Reperfusion Injury in Cholestatic Rat Liver: Hope for Marginal Livers

et al. 2011

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Cholestasis is a significant risk factor for immediate hepatic failure due to ischemia reperfusion (I/R) injury in patients undergoing liver surgery or transplantation. We recently demonstrated that inhibition of Hedgehog (Hh) signaling with cyclopamine (CYA) before I/R prevents liver injury. In this study we hypothesized that Hedgehog (Hh) signaling may modulate I/R injury in cholestatic rat liver. Cholestasis was induced by bile duct ligation (BDL). Seven days after BDL, rats were exposed to either CYA or vehicle for 7 d daily before subjecting them to 30 min of ischemia and 4 h of reperfusion. Expression of Hh ligands (sonic hedgehog, Patched-1 and Glioblastoma-1), assessment of liver injury, neutrophil infiltration, cytokines, lipid peroxidation, cell proliferation and apoptosis were determined. Significant upregulation of Hh ligands was seen in vehicle treated BDL rats. I/R injury superimposed on these animals resulted in markedly elevated serum alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin accompanied with increased neutrophil recruitment and lipid peroxidation. Preconditioning with CYA reduced the histological damage and serum liver injury markers. CYA also reduced neutrophil infiltration, proinflammatory cytokines such as TNF-α and IL-1β expression of α-smooth muscle actin and Type 1 collagen resulting in reduced fibrosis. Furthermore CYA treated animals showed reduced cholangiocyte proliferation, and apoptosis. Hepatoprotection by CYA was conferred by reduced activation of protein kinase B (Akt) and extracellular signal regulated kinase (ERK). Endogenous Hh signaling in cholestasis exacerbates inflammatory injury during liver I/R. Blockade of Hh pathway represents a clinically relevant novel approach to limit I/R injury in cholestatic marginal liver.

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“…In the longer term, nonanastomotic biliary strictures and an increased incidence of acute and chronic rejection have been attributed to the consequences of this reperfusion injury. The shortage of organs available for OLT has resulted in an increasing use of marginal donor livers that include steatotic livers that have a lower tolerance for hypoxia and a greater susceptibility to reperfusion injury (3,4).…”

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confidence: 99%

A Study of the Metabolites of Ischemia-Reperfusion Injury and Selected Amino Acids in the Liver Using Microdialysis during Transplantation

et al. 2005

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These data may represent "normal" changes seen in the immediate posttransplant period because all grafts functioned well. Two important metabolic fates of arginine in the liver are in the detoxification of ammonia by means of the urea cycle, and in the synthesis of nitric oxide (NO). Low extracellular arginine may reflect influx of the amino acid into hepatocytes, resulting in formation of NO in the presence of inducible NO synthase or conversion to ornithine in the presence of arginase in the urea cycle. As the organ stabilizes, restriction of arginine uptake may give rise to the observed increase in extracellular arginine.

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Use of marginal donors

Cited by 12 publications

References 50 publications

Transplantation for Primary Biliary Cirrhosis: Retrospective Analysis of 400 Patients in A Single Center

Transplantation for Primary Biliary Cirrhosis: Retrospective Analysis of 400 Patients in A Single Center

Cyclopamine Attenuates Acute Warm Ischemia Reperfusion Injury in Cholestatic Rat Liver: Hope for Marginal Livers

A Study of the Metabolites of Ischemia-Reperfusion Injury and Selected Amino Acids in the Liver Using Microdialysis during Transplantation

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