The Predictive Value of Donor Liver Biopsies for the Development of Primary Nonfunction After Orthotopic Liver Transplantation

D’Alessandro, Anthony M.; Kalayoğlu, Münci; Sollinger, Hans W.; Hoffmann, Robert M.; Reed, Alan; Knechtle, Stuart J.; Pirsch, John D.; Hafez, G. Reza; Lorentzen, David; Belzer, Folkert O.

doi:10.1097/00007890-199101000-00024

Cited by 394 publications

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“…[21][22][23] In experimental situations, both genetic-based models and high-fat-diet-induced model proved that preexisting steatosis caused significant impairment of liver regeneration after PH. 12,24,25 In addition, the augmented hepatic steatosis after PH coexisted with the defective liver regeneration after PH in mice.…”

Section: Discussionmentioning

confidence: 99%

“…13 However, It is well established that excessive lipid accumulation in liver exhibits profound impairment of liver regeneration after PH. 12,[21][22][23][24][25] Adiponectin functions as a hormone to stimulate lipid catabolism. 26 It reduces lipid accumulation by inhibiting hepatic lipogenesis and stimulating fatty acid oxidation.…”

Section: The Effect Of Adiponectin Deficiency On Liver Mass Restoratimentioning

confidence: 99%

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Adiponectin deficiency impairs liver regeneration through attenuating STAT3 phosphorylation in mice

Shu

Zhang

Wang

et al. 2009

Laboratory Investigation

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Liver regeneration is a very complex and well-orchestrated process associated with signaling cascades involving cytokines, growth factors, and metabolic pathways. Adiponectin is an adipocytokine secreted by mature adipocytes, and its receptors are widely distributed in many tissues, including the liver. Adiponectin has direct actions in the liver with prominent roles to improve hepatic insulin sensitivity, increase fatty acid oxidation, and decrease inflammation. To test the hypothesis that adiponectin is required for normal progress of liver regeneration, 2/3 partial hepatectomy (PH) was performed on wild-type and adiponectin-null mice. Compared to wild-type mice, adiponectin-null mice displayed decreased liver mass regrowth, impeded hepatocyte proliferation, and increased hepatic lipid accumulation. Gene expression analysis revealed that adiponectin regulated the gene transcription related to lipid metabolism. Furthermore, the suppressed hepatocyte proliferation was accompanied with reduced signal transducer and activator of transcription protein 3 (STAT3) activity and enhanced suppressor of cytokine signaling 3 (Socs3) transcription. In conclusion, adiponectin-null mice exhibit impaired liver regeneration and increased hepatic steatosis. Increased expression of Socs3 and subsequently reduced activation of STAT3 in adiponectin-null mice may contribute to the alteration of the liver regeneration capability and hepatic lipid metabolism after PH. The liver has a central role in metabolic homeostasis, as it is responsible for the metabolism, synthesis, storage, and redistribution of nutrients, carbohydrates, fats, and vitamins. Paradoxically, it is also the main detoxifying organ of the body, which is frequently challenged by chemical, traumatic, or infectious injuries. Consequently, the liver has evolved a unique ability to regenerate in respond to liver mass loss because of injuries. 1,2 Liver regeneration, which is driven by the replication of existing hepatocytes, is a process of compensatory hyperplasia rather than a differentiation process of stem cells. 3 One of the most effective models for studying liver regeneration after hepatocellular loss is partial hepatectomy (PH) in rodents. This technique, which was first described by Higgins and Anderson and performed in rats, 4 can be modified to be safely and reproducibly performed in mice. 5 After PH, resection of about 2/3 of liver mass results in quiescent hepatocytes rapidly re-entering the cell cycle. This highly regulated process is primed by different cytokines and growth factors that activate the downstream kinases and transcription factors. As a result, the hepatocytes initiate the transcription of more than 100 early genes, accumulate triglyceride and cholesterol to supply the energy and materials required for restore the liver mass. After one or two rounds of replication of hepatocytes, the original liver mass is restored within 5-7 days. Thus, liver regeneration constitutes a unique model to study signal transduction, lipid metabolism, and cell cycl...

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Section: Discussionmentioning

confidence: 99%

Section: The Effect Of Adiponectin Deficiency On Liver Mass Restoratimentioning

confidence: 99%

Adiponectin deficiency impairs liver regeneration through attenuating STAT3 phosphorylation in mice

Shu

Zhang

Wang

et al. 2009

Laboratory Investigation

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“…5 The severity of the injury related to cold preservation in our center, however, could be limited because of our policy of limiting cold preservation times. 28,29 Rewarming and oxygenated reperfusion during the implantation phase of OLT is a well-described factor in liver injury. 30 Recent studies have shown a narrow balance between cell death during preservation and reperfusion, followed by cell proliferation through regeneration.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Rewarming Time During Allograft Implantation Predisposes to Recurrent Hepatitis C Infection After Liver Transplantation

Baron

Sindram

Higdon

et al. 2000

Liver Transplantation

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The majority of patients undergoing orthotopic liver transplantation (OLT) have end-stage liver disease secondary to hepatitis C virus (HCV) infection. Although OLT does not cure the disease and recurrent virus is present in all patients, relatively few patients with recurrent viremia develop clinical disease. When the disease recurs, however, the results can be devastating. Factors associated with increased risk for recurrent HCV disease remain controversial. We hypothesized that preservation injury may predispose to the severity of HCV disease after OLT. We reviewed our series of OLTs performed for HCV cirrhosis between January 1994 and December 1998 (n ‫؍‬ 56; 62 transplants). Patients were grouped according to the severity of recurrent hepatitis C. Group 1 had no or mild HCV disease (n ‫؍‬ 36), and group 2 had moderate to severe HCV disease (n ‫؍‬ 20). The duration of ischemic rewarming during graft implantation was significantly associated with the severity of recurrent hepatitis C (P F .04). The estimated chances of severe disease within the first year post-OLT after 30, 60, or 90 minutes of ischemic rewarming time were 19%, 40%, and 65%, respectively. Cold ischemia time, transaminase levels, and prothrombin time did not correlate with the severity of hepatitis C. In conclusion, our data suggest that the duration of ischemic rewarming predisposes to severe recurrent hepatitis C. This finding warrants the investigation of the pathogenesis of recurrent HCV disease after ischemic injury. Reduction of rewarming time should be stressed in OLT, particularly in patients with HCV cirrhosis. (Liver Transpl 2000;6:407-412.)A pproximately 1% of Americans (2.7 million individuals) are currently infected with the hepatitis C virus (HCV). 1 Although the natural history of the viral infection is unknown, it is estimated that chronic hepatitis caused by HCV infection develops in approximately 20% of infected individuals 20 years after initial exposure. 2-4 Patients with chronic HCV have an increased risk for hepatocellular carcinoma (1% to 4% per year) and the complications of end-stage liver disease. In these patients, the survival rate with decompensated cirrhosis is 50% at 5 years without transplantation. Orthotopic liver transplantation (OLT) for these patients leads to 5-year survival rates between 73% and 81%. 5,6 As a result of these data, patients with decompensated HCV cirrhosis should be considered for liver replacement therapy, as well as medical treatment, for better long-term survival. HCV-associated cirrhosis was the predominant indication for OLT in patients who underwent transplantation in the United States between 1987 and 1995. 7 Currently, hepatitis C is the indication for transplantation in more than 30% of adults, making it the most common indication for OLT. 8 Although several studies have suggested that the long-term survival rate after OLT in patients with HCV cirrhosis is not different from those who undergo OLT for other indications, 5,6,9,10 all patients have recurrent HCV infection at 1 year ...

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“…35,36 Causes are varied and include obesity, older age, alcoholism, diabetes mellitus, and postmortem nutritional changes. 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.…”

Section: Steatotic Donorsmentioning

confidence: 99%

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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The Predictive Value of Donor Liver Biopsies for the Development of Primary Nonfunction After Orthotopic Liver Transplantation

Cited by 394 publications

References 0 publications

Adiponectin deficiency impairs liver regeneration through attenuating STAT3 phosphorylation in mice

Adiponectin deficiency impairs liver regeneration through attenuating STAT3 phosphorylation in mice

Prolonged Rewarming Time During Allograft Implantation Predisposes to Recurrent Hepatitis C Infection After Liver Transplantation

The utility of marginal donors in liver transplantation

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