Use of Livers With Microvesicular Fat Safely Expands the Donor Pool

Fishbein, T.; Fiel, M. Isabel; Emre, Sükrü; Çubukçu, Olcay; Guy, Stephen R.; Schwartz, Myron; Miller, Crystal; Sheiner, Patricia A.

doi:10.1097/00007890-199707270-00012

Cited by 261 publications

(192 citation statements)

References 5 publications

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“…Histologic patterns in donor livers show two types of steatosis, a diffuse small droplet vacuolization or microsteatosis without macrovesicular deposit, and a combined pattern of large and small vacuole deposits or macrosteatosis. 37,38 Fat accumulation in the cytoplasm of hepatocytes is associated with an increase in cell volume, which may result in partial or complete obstruction of the hepatic sinusoidal space. 39 Furthermore, animal studies have shown that fatty livers experience greater reduction in energy stores during cold storage and have a decreased capacity to restore ATP levels after reperfusion.…”

Section: Steatotic Donorsmentioning

confidence: 99%

“…Recent studies have reported adequate function of livers with microvescicular steatosis. 37,38,45,46 Clinically, recipients who receive grafts with moderate steatosis (Ͼ25% to 30%) have impaired early graft function in the first 3 days as reflected by a higher peak serum glutamic oxaloacetic transaminase, lower bile output, and increased intraoperative bleeding. Marsman et al 47 transplanted 59 livers with up to 30% fat and compared them to time-matched controls; the fatty liver group had a decreased 4-month graft survival and a decreased 2-year patient survival.…”

Section: Steatotic Donorsmentioning

confidence: 99%

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The utility of marginal donors in liver transplantation

Busuttil¹

2003

Liver Transplantation

629

508

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The shortage of organs has led centers to expand their criteria for the acceptance of marginal donors. The combination of multiple marginal factors seems to be additive on graft injury. In this review, the utility of various marginal donors in patients requiring liver transplantation will be described, including older donors, steatotic livers, non-heart-beating donors, donors with viral hepatitis, and donors with malignancies. The pathophysiology of the marginal donor will be discussed, along with strategies for minimizing the ischemia reperfusion injury experienced by these organs. Finally, new strategies for improving the function of the marginal/expanded donor liver will be reviewed. (Liver Transpl 2003;9:651-663.)

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Section: Steatotic Donorsmentioning

confidence: 99%

Section: Steatotic Donorsmentioning

confidence: 99%

The utility of marginal donors in liver transplantation

Busuttil¹

2003

Liver Transplantation

629

508

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“…8,9 However, some studies demonstrated that the risk for complications in transplantation utilizing organs with mild steatosis was overestimated and this may enlarge the pool of potential donor organs. 10,11 Additionally, liver regeneration after partial hepatectomy (PHx) in mice and rats is associated with hepatic lipid accumulation and includes activation of inflammationrelated signaling molecules, such as interleukin 6 (IL-6), nuclear factor kappa B (nFkB) and signal transducer and activator of transcription-3 (STAT3). [12][13][14][15] Therefore, we aimed to investigate if steatosis alone (i) enhances vulnerability of the liver to damage, (ii) impairs proliferation and regeneration after PHx and (iii) which mechanisms are involved in this enhanced susceptibility.…”

mentioning

confidence: 99%

Steatosis does not impair liver regeneration after partial hepatectomy

Sydor

Schlattjan

et al. 2013

Laboratory Investigation

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Hepatic steatosis is a key feature of non-alcoholic fatty liver disease (NAFLD). While storage of lipid droplet-bound triglycerides in simple steatosis is physiologically inert, non-alcoholic steatohepatitis (NASH) is associated with hepatocyte damage and apoptosis. Mitochondrial oxidation of free fatty acids (FFA), derived from lipid droplets and hepatocellular uptake, is a rapid and effective way of energy supply for proliferating cells and FFA esterification provides substrates for lipid synthesis and cell proliferation. Thus, we investigated whether simple steatosis induced by western diet (WD) improves liver regeneration after partial hepatectomy (PHx). WD feeding for 6 weeks caused simple steatosis with hepatic lipid droplet and triglyceride accumulation accompanied by induction of fatty acid transport proteins (FATP), death receptors (DR), pro-and anti-apoptotic genes, hepatocyte growth factor (Hgf ) as well as increased serum leptin levels in a mouse model. After PHx, liver cell proliferation was higher in WD-fed mice and associated with FATP and Hgf induction. In addition, Erk1/2 (extracellular-related MAP kinase 1/2) dephosphorylation observed in standard diet (SD) mice was reduced in WD animals. PHx in steatotic livers did not affect hepatocyte apoptosis, despite DR upregulation. WD-induced steatosis enhances liver cell proliferation, which is accompanied by increased Hgf and leptin signaling as well as Erk1/2 phosphorylation. Induction of mild steatosis may therefore be beneficial for surgical outcome of hepatectomies.

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“…4,6 High degrees of macrosteatosis are known risk factors of primary nonfunction; grafts with severe macrosteatosis are no longer recommended to be used, 7 whereas a safe use of microsteatotic organs has been reported. 8 Essential fatty acids include two classes, n-3 and n-6 polyunsaturated fatty acids (PUFA). They are not interconvertible, are metabolically and functionally distinct, and often have important opposing physiological functions; therefore, their balance is essential for health.…”

mentioning

confidence: 99%

Prevention of reperfusion injury and microcirculatory failure in macrosteatotic mouse liver by omega‐3 fatty acids†‡

et al. 2007

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Macrovesicular hepatic steatosis has a lower tolerance to reperfusion injury than microvesicular steatosis with an abnormally high ratio of omega-6 (n-6): omega-3 (n-3) polyunsaturated fatty acids (PUFAs). We investigated the influence of PUFAs on microcirculation in steatotic livers and the potential to minimize reperfusion injury in the macrosteatotic liver by normalization of PUFAs. Ob/ob mice were used as a model of macrovesicular hepatic steatosis and C57/Bl6 mice fed a choline-deficient diet for microvesicular steatosis. Steatotic and lean livers were subjected to 45 minutes of ischemia and 3 hours of reperfusion. Hepatic content of omega-3 and omega-6 PUFAs was determined. Microcirculation was investigated using intravital fluorescence microscopy. A second group of ob/ob mice was supplemented with dietary omega-3 PUFAs and compared with the control diet-fed group. Microcirculation, AST, and Kupffer cell activity were assessed. Macrosteatotic livers had significant microcirculatory dysfunction correlating with high omega-6: omega-3 PUFA ratio. Dietary omega-3 PUFA resulted in normalization of this ratio, reduction of intrahepatic lipids, and decrease in the extent of macrosteatosis. Defective microcirculation was dramatically ameliorated with significant reduction in Kupffer cell activity and protection against hepatocellular injury both before ischemia and after reperfusion. Conclusion: Macrosteatotic livers disclosed an abnormal omega-6: omega-3 PUFA ratio that correlates with a microcirculatory defect that enhanced reperfusion injury. Thus, protective strategies applied during or after ischemia are unlikely to be useful. Preoperative dietary omega-3 PUFAs protect macrosteatotic livers against reperfusion injury and might represent a valuable method to expand the live liver donor pool. (

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Use of Livers With Microvesicular Fat Safely Expands the Donor Pool

Cited by 261 publications

References 5 publications

The utility of marginal donors in liver transplantation

The utility of marginal donors in liver transplantation

Steatosis does not impair liver regeneration after partial hepatectomy

Prevention of reperfusion injury and microcirculatory failure in macrosteatotic mouse liver by omega‐3 fatty acids†‡

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