Short- and long-term outcomes after steatotic liver transplantation.
ABSTRACT To determine if the use of steatotic grafts adversely affects outcomes in liver transplantation.
A retrospective review of a prospectively maintained database.
A single center.
Four hundred ninety adults who underwent liver transplantation from January 1, 2002, to December 31, 2008, at a single center. Graft biopsies were available in 310 (63.3%) cases. Grafts were classified based on amount of macrovesicular steatosis: 5% or less (n = 222), more than 5% to less than 35% (n = 66), and 35% or more (n = 22).
Recipient demographics, Model for End-Stage Liver Disease (MELD) score, patient/graft survival, complications, transfusion rates, and liver function test results.
One-, 3-, and 5-year patient and graft survivals, respectively, were similar (90.38%, 84.7%, and 74.4%, respectively, P = .3; and 88.7%, 82.5%, and 73.3%, respectively, P = .15). Median follow-up was 25 months. Recipient age, sex, body mass index, laboratory MELD score, and ischemia times were similar among all groups. Packed red blood cell (3 vs 8 U, P < .001), fresh frozen plasma (2 vs 4 U, P = .007), and cryoprecipitate transfusion rates were significantly increased in grafts with 35% or more steatosis. Intensive care unit (5 vs 11 days, P = .02) and hospital (11 vs 21 days, P < .001) stay was also increased in those with grafts with 35% or more steatosis compared with those with 5% or less steatosis. The grafts with 35% or more steatosis had higher transaminase peaks and longer times for bilirubin to normalize (P < .001).
Use of carefully selected steatotic grafts was not associated with higher rates of primary nonfunction or poorer outcomes. However, the use of steatotic grafts is associated with increased resource use in the perioperative period.
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ABSTRACT: Liver ischemia and reperfusion (I/R) injury is characterized by oxidative stress that is accompanied by alterations of the endogenous defensive system. Emerging evidence suggests a protective role for autophagy induced by multiple stressors including reactive oxygen species. Meanwhile, heme oxygenase-1 (HO-1) has long been implicated in cytoprotection against oxidative stress in vitro and in vivo. Therefore, we investigated the impact of autophagy in the pathogenesis of liver I/R and its molecular mechanisms, particularly its linkage to HO-1. By using transmission electron microscopic analysis and biochemical autophagic flux assays with microtubule-associated protein 1 light chain 3-II, and beclin-1, representative autophagy markers, and p62, a selective substrate for autophagy, we found that reperfusion reduced autophagy both in the rat liver and in primary cultured hepatocytes. When autophagy was further inhibited with chloroquine or wortmannin, I/R-induced hepatocellular injury was aggravated. While livers that underwent I/R showed increased levels of mammalian target of rapamaycin and calpain 1 and 2, inhibition of calpain 1 and 2 induced an autophagic response in hepatocytes subjected to hypoxia/reoxygenation. HO-1 increased autophagy, and HO-1 reduced I/R-induced calcium overload in hepatocytes and prevented calpain 2 activation both in vivo and in vitro. Taken together, these findings suggests that the impaired autophagy during liver I/R, which is mediated by calcium overload and calpain activation, contributes to hepatocellular damage and the HO-1 system protects the liver from I/R injury through enhancing autophagy.Free Radical Biology and Medicine 12/2013; DOI:10.1016/j.freeradbiomed.2013.12.014 · 5.27 Impact Factor
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ABSTRACT: A 45 year old female with a body mass index (BMI) of 24 underwent successful liver transplantation (LT) for alcoholic cirrhosis using a donor liver from an obese woman with microvesicular steatosis (80%) and minimal macrovesicular steatosis (5-10%) on liver biopsy. Ascites and hepatosplenomegaly developed soon after LT with progressive increase of serum alkaline phosphatase to 1340 IU/L while aspartate aminotransferase (AST), and alanine transaminase (ALT), and total bilirubin remained normal. Imaging showed marked hepatomegaly, extensive fatty infiltration of the liver, and compression of the hepatic veins with narrowing of the intrahepatic inferior vena cava (IVC). Liver biopsy on post-operative day 39 revealed 90-100% macrovesicular steatosis, steatohepatitis, and portal fibrosis. A hepatic venogram showed a 10 cm segment of intrahepatic IVC stenosis that was stented, improving portal venous pressure measurements. However, portal hypertension requiring diuretic therapy and multiple paracenteses remained. By 3 months after LT, her liver had grown to 22 cm, transaminases increased 2-4 times the upper limit of normal with a 2:1 AST to ALT ratio. Liver biopsy at post-LT day 82 showed no change in steatosis and steatohepatitis despite corticosteroid withdrawal and interval periportal and perisinusoidal fibrosis. 12 weeks after LT, the patient was found to have low apolipoprotein B (65 mg/dL), high-density lipoprotein (HDL) (<10 mg/dL), low-density lipoproteins (LDL) (9 mg/dL), and total cholesterol (<50 mg/dL) levels. Therapy was started for NASH with high dose (800 IU daily) vitamin E and pioglitazone 15 mg daily, and she received topical vegetable oil and oral essential fatty acid supplements. Liver enzymes normalized after 3 months and her lipid profile improved markedly (HDL 27 mg/dL, total cholesterol 128 mg/dL), with progressive decrease in liver size and resolution of ascites after 5 months of therapy. At 2 years post-LT, the liver enzymes remain normal and lipids have normalized.03/2013; 3(1):70-74. DOI:10.1016/j.jceh.2013.01.001
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ABSTRACT: Liver transplantation is the only life-saving therapeutic option for end-stage liver disease. Progressive donor organ shortage and declining donor organ quality justify the evaluation of the leverage of the Donor-Risk-Index, which was recently adjusted to the Eurotransplant community's requirements (ET-DRI). We analysed the prognostic value of the ET-DRI for the prediction of outcome after liver transplantation in our center within the Eurotransplant community. 291 consecutive adult liver transplants were analysed in a single centre study with ongoing data collection. Determination of the area under the receiver operating characteristic curve (AUROC) was performed to calculate the sensitivity, specificity, and overall correctness of the Eurotransplant-Donor-Risk-Index (ET-DRI) for the prediction of 3-month and 1-year mortality, as well as 3-month and 1-year graft survival. Cut-off values were determined with the best Youden-index. The ET-DRI is unable to predict 3-month mortality (AUROC: 0.477) and 3-month graft survival (AUROC: 0.524) with acceptable sensitivity, specificity and overall correctness (54% and 56.3%, respectively). Logistic regression confirmed this finding (p = 0.573 and p = 0.163, respectively). Determined cut-off values of the ET-DRI for these predictions had no significant influence on long-term patient and graft survival (p = 0.230 and p = 0.083, respectively; Kaplan-Meier analysis with Log-Rank test). The ET-DRI should not be used for donor organ allocation policies without further evaluation, e.g. in combination with relevant recipient variables. Robust and objective prognostic scores for donor organ allocation purposes are desperately needed to balance equity and utility in donor organ allocation.Journal of Negative Results in BioMedicine 12/2013; 12(1):18. DOI:10.1186/1477-5751-12-18 · 1.47 Impact Factor