High-density single-nucleotide polymorphism (SNP)

High-density single-nucleotide polymorphism (SNP) selleck screening library arrays now provide the possibility of defining genome-wide copy number changes.8, 9 Additionally, there has been little progress in determining specific genes targeted by various common copy number gains and losses, in part due to limited availability of complementary transcriptional data on sufficient numbers of specimens to focus on a small list of candidate genes. Although

several studies have been conducted to define potential cancer genes through combined analyses of genomic alterations and transcriptomes in HCC, they are constrained by the use of different sets and small sizes of tumor samples or by the use of relatively lower-resolution platforms.10-12 In this study we applied a whole-genome SNP 6.0 array to define a comprehensive copy number profile of 58 paired HCC and nontumor tissues. We further identified potential cancer genes by adopting a combined approach to define somatic CNAs and transcriptomes in the same set of paired HCC specimens. AFP, alpha-fetoprotein; CNA, copy number alteration; DEG, differentially expressed gene; HCC, hepatocellular carcinoma; HEY1, hairy/enhancer-of-split related with YRPW motif 1; IHC, immunohistochemistry; q-PCR, quantitative real-time polymerase chain reaction;

siRNA, small interfering RNA; SNP, single nucleotide polymorphism; SNRPE, small nuclear ribonucleoprotein polypeptide E; TRIM35, tripartite

motif-containing 35. Methods and JQ1 any associated references are available in the Supporting Materials. We analyzed the hybridization signal intensities of 58 paired HCC and nontumor tissues from the same individuals to identify regions of somatically generated CNAs. A total of 2,206 CNAs were identified in the 58 HCC genomes. A genome-wide view of segmented copy numbers revealed that most chromosomal arms undergo either see more copy number gain or loss in a large proportion of the samples (Fig. 1A). The 2,206 CNAs spanned from 0.28 kb to 30 Mb in size (median, 6.22 Mb). There was a mean of 38 CNAs per HCC genome and copy number gains were more commonly observed than losses (1.9:1). To find evidence of driver alterations in tumor genomes we further evaluated the recurrent regions of copy number gains and losses using the following parameters: the minimum physical length of putative CNAs was more than 100 kb; the CNAs was present in at least three tumor samples; and finally, the overlapping common regions among multiple tumors were calculated. Accordingly, a total of 1,241 significant CNAs were obtained, including 963 amplifications and 278 deletions (Fig. 1B). These regions were highly concordant with previous findings, including the recurrent gains at 1q, 6p, 7q, 8q, 11q, 17q, and 20q and recurrent losses at 4q, 8p, 16q, and 17p.

The tumor volume of shASPP1 or shASPP2 modified HCC-LM3 xenograft

The tumor volume of shASPP1 or shASPP2 modified HCC-LM3 xenografts was 52% or 72% larger than that of shNon-treated xenografts 30 days after implantation (Fig. 5E). To investigate the effects of ASPP1 and ASPP2 on apoptosis, ASPP1 and ASPP2 genes were transfected into HCC cells with different p53 status. Serum-starvation caused a 3-fold increase of apoptotic cells in HCC-LM3 cells that had endogenous wildtype p53. Overexpression of p53 did not further enhance apoptosis

in HCC-LM3 cells. In contrast, overexpression of ASPP1 and ASPP2 caused 100% and 70% increases of apoptotic cells, respectively (Fig. 6A). This indicates that ASPP1 and ASPP2 could enhance apoptosis in HCC cells harboring the wildtype p53 gene. Interestingly, introduction of ASPP2 but not ASPP1 into Hep3B cells with p53 selleck gene null induced apoptosis to a similar level as p53 did under serum-starvation (Fig. 6B). Introduction of ASPP1 and ASPP2 genes into Huh-7 with p53220Cys induced apoptosis to an extent similar to that of p53 (Fig. 6C). Knock-down of ASPP1 or buy BIBW2992 ASPP2 significantly reduced the apoptotic cells induced by serum starvation in HepG2 or HCC-LM3 cells that had wildtype p53 (Fig. 6D) and attenuated cisplatin-induced apoptosis in HepG2 cells (Fig. 6E). Consistent with

the in vitro experimental results, fewer apoptotic cells were found in HCC-LM3 xenografts with shASPP1 or shASPP2 treatment (Fig. 6F). These data indicate that down-regulation of ASPP1 and ASPP2 in HCC may promote tumor progression through inhibition of cell apoptosis. Dysregulation of apoptosis is closely related to the expansion of tumor cells, metastasis, and resistance to chemotherapy.26–28p53 is a key regulator for apoptosis and frequently mutates in various human cancers.29 The proapoptotic function of p53 is closely linked to its antitumor effects. All of the tumor-derived p53 mutants have lost their ability to induce apoptosis. However, only 30% of HCC contains p53 gene mutations. It remains unclear why wildtype p53 fails to suppress tumor growth in the remaining 70% of HCC. ASPP1 and ASPP2 proteins interact

with p53 and its selleck screening library family members, p63 and p73, to promote apoptosis.1, 3 In this study we describe for the first time that ASPP1 and ASPP2 genes are frequently inactivated by hypermethylation in HCC that is HBV-positive. In HCC tumor tissues, ASPP1 and ASPP2 were frequently found methylated, which contributed to the down-regulation of ASPP1 and ASPP2 in HCCs. Importantly, methylation of ASPP1 and ASPP2 in the surrounding nontumor tissues was closely related to the size and the stage of HCCs. A previous study showed that ASPP1 and ASPP2 were frequently down-regulated in breast cancer expressing wildtype p53.1 In this study we found that HCC tumors with the p53 gene wildtype more frequently had ASPP1 and/or ASPP2 gene methylation.

There was up-reg-ulation of transforming growth factor-β in bilia

There was up-reg-ulation of transforming growth factor-β in biliary epithelial cells and blocking OPN, transforming Hormones antagonist growth factor-β or both reduced collagen-I expression in hepatic stellate cells. Conclusion: OPN emerges as a key matricellular cytokine driving ductular reaction and

contributing to scarring and liver fibrosis via transforming growth factor-β. Disclosures: The following people have nothing to disclose: Xiaodong Wang, Aritz Lopategi, Yongke Lu, Naoto Kitamura, Xiaodong Ge, Raquel Urtasun, Tung Ming Leung, M. Isabel Fiel, Natalia Nieto Congenital hepatic fibrosis (CHF), the most common extra-hepatic manifestation of autosomal recessive polycystic kidney disease (ARPKD), is associated with excessive extracellular matrix (ECM) deposition which encapsulates ductal plate cell-derived cysts. The precise mechanisms of hepatic cystogenesis and associated CHF are not known. Therapeutic options for ARPKD/CHF are extremely limited. Here, making use Rucaparib price of the polycystic kidney (PCK) rat which harbors the same mutation found in ARPKD patients, we characterized the development of hepatic fibrosis from post natal day (PND) 0 to 3 months after birth.

Sprague-Dawley (SD) rats were used as controls. Liver to body weight ratios were greater in PCK rats compared to controls, consistent with the development and growth of intrahep-atic cysts. At three months, PCK rats had increased hepatic mRNA accumulation of αSMA (myofibroblast marker), type I collagen, elastin (portal fibroblast marker), desmin (hepatic stellate cell marker) and connective tissue growth factor (CTGF) compared to SD rats. Consistent with those findings, 3-month old PCK rats exhibited increased type 1 collagen, Sirius red staining and CTGF protein relative to SD rats. Time

course analysis revealed that the peak hepatic mRNA accumulation of αSMA, Col 1a 1, CTGF and elastin was at PND 10-20. Hepatic αSMA protein also peaked at PND selleck screening library 10. Hepatic CTGF mRNA and protein was induced in PCK rats at PND5, peaked at PND10 and remained increased throughout the time course. While cysts were observable PND 0, diffuse ECM deposition around hepatic cysts revealed by Sirius red staining began PND 5 in PCK rats; diffuse Sirius red staining increased until PND 20. In PND 30 and 3-month old PCK rats, Sirius red staining became intense and compressed around proliferating cysts. The increased hepatic fibrosis observed in PCK rat livers was corroborated by observations made in human PKD liver samples. Collectively, these data suggest that initiation of fibrogenesis in PCK rats occurs during early postnatal period and involves both portal fibroblast- and hepatic stellate cell-derived myofibroblasts. Furthermore, these data suggest that CTGF may be a driving force behind CHF in the PKC rat and reveal CTGF as a potential therapeutic target. These studies were supported by grants to U.A. and D.P.W. (P50 DK057301-11) and M.T.P (P20 GM103549 and R00 AA017918).

There was up-reg-ulation of transforming growth factor-β in bilia

There was up-reg-ulation of transforming growth factor-β in biliary epithelial cells and blocking OPN, transforming GSK126 growth factor-β or both reduced collagen-I expression in hepatic stellate cells. Conclusion: OPN emerges as a key matricellular cytokine driving ductular reaction and

contributing to scarring and liver fibrosis via transforming growth factor-β. Disclosures: The following people have nothing to disclose: Xiaodong Wang, Aritz Lopategi, Yongke Lu, Naoto Kitamura, Xiaodong Ge, Raquel Urtasun, Tung Ming Leung, M. Isabel Fiel, Natalia Nieto Congenital hepatic fibrosis (CHF), the most common extra-hepatic manifestation of autosomal recessive polycystic kidney disease (ARPKD), is associated with excessive extracellular matrix (ECM) deposition which encapsulates ductal plate cell-derived cysts. The precise mechanisms of hepatic cystogenesis and associated CHF are not known. Therapeutic options for ARPKD/CHF are extremely limited. Here, making use BYL719 clinical trial of the polycystic kidney (PCK) rat which harbors the same mutation found in ARPKD patients, we characterized the development of hepatic fibrosis from post natal day (PND) 0 to 3 months after birth.

Sprague-Dawley (SD) rats were used as controls. Liver to body weight ratios were greater in PCK rats compared to controls, consistent with the development and growth of intrahep-atic cysts. At three months, PCK rats had increased hepatic mRNA accumulation of αSMA (myofibroblast marker), type I collagen, elastin (portal fibroblast marker), desmin (hepatic stellate cell marker) and connective tissue growth factor (CTGF) compared to SD rats. Consistent with those findings, 3-month old PCK rats exhibited increased type 1 collagen, Sirius red staining and CTGF protein relative to SD rats. Time

course analysis revealed that the peak hepatic mRNA accumulation of αSMA, Col 1a 1, CTGF and elastin was at PND 10-20. Hepatic αSMA protein also peaked at PND find more 10. Hepatic CTGF mRNA and protein was induced in PCK rats at PND5, peaked at PND10 and remained increased throughout the time course. While cysts were observable PND 0, diffuse ECM deposition around hepatic cysts revealed by Sirius red staining began PND 5 in PCK rats; diffuse Sirius red staining increased until PND 20. In PND 30 and 3-month old PCK rats, Sirius red staining became intense and compressed around proliferating cysts. The increased hepatic fibrosis observed in PCK rat livers was corroborated by observations made in human PKD liver samples. Collectively, these data suggest that initiation of fibrogenesis in PCK rats occurs during early postnatal period and involves both portal fibroblast- and hepatic stellate cell-derived myofibroblasts. Furthermore, these data suggest that CTGF may be a driving force behind CHF in the PKC rat and reveal CTGF as a potential therapeutic target. These studies were supported by grants to U.A. and D.P.W. (P50 DK057301-11) and M.T.P (P20 GM103549 and R00 AA017918).

Inostroza, Helene Poels, Roberto Troisi, Jean Del-waide, Sven M

Inostroza, Helene Poels, Roberto Troisi, Jean Del-waide, Sven M. Francque, Vincent Donckier BACKGROUND: Tertiary care liver transplant centers frequently

receive requests from outlying hospitals to transfer patients with acute decompensated cirrhosis for a higher level of care, including evaluation for liver transplantation. There have been no published studies looking at clinical outcomes for patients with acute decompensated cirrhosis who are transferred to a liver transplant center or barriers to efficient interhospital transfer. AIM: To determine the rate of liver transplantation Belinostat molecular weight and mortality for patients with acute decompensated cirrhosis transferred from outlying hospitals to a tertiary care liver transplant center and elucidate barriers to timely interhospital transfer. METHODS: Patients 18 years of age or older transferred from an outlying hospital to Strong PF-01367338 order Memorial Hospital (SMH) for management of acute decompensated cirrhosis between January

1, 2011 and July 31, 2013 were identified by interrogation of the hospital’s transfer request logs. Patients less than 18 years of age or those transferred for management of fulminant hepatic failure were excluded. RESULTS: 99 patients were identified, including 7 patients who were transferred multiple times. Mean length of stay (LOS) at the outside hospital (OSH) was 6.8 days this website (range 0-38 days). Mean time from transfer request to arrival at SMH was 1.2 days (range 0-18 days). There were 30 cases of interhospital transfer delay in which 30% of cases were due to lack of bed availability while 13% of cases were due to the patient being too unstable to transfer. 13 of 99 (13%) patients were evaluated and listed for liver transplantation;

3 (3%) of these patients underwent liver transplantation during their admission while 7 others died in the hospital. 29 of 92 (32%) patients died during their initial admission after a mean LOS of 19.7 days (range 4-99 days). 2 additional patients died after being transferred on a separate occasion. Mean peak OSH MELD score for patients who died at SMH was 31.3 (range 20-41). CONCLUSIONS: Very few patients with acute decompensated cirrhosis transferred from an outlying hospital were suitable for liver transplantation and an even smaller number of patients were transplanted. A substantial number of patients died following a prolonged hos-pitalization. The major reason for delay of transfer was lack of bed availability. Given limited resources and costs associated with transferring patients to a tertiary care liver transplant center, patient selection for transfer is crucial in order to provide optimal care and allocate resources appropriately.

PEGylated coagulation proteins for haemophilia A and B are under

PEGylated coagulation proteins for haemophilia A and B are under development with the goal of prolonging the circulation half-life and thereby offering extended protection from bleeding.

Bleeding events in haemophilia A are currently treated with on demand or frequent prophylactic infusions (up to three times per week or every other day) with recombinant or plasma-derived FVIII [15]. Prolongation of half-life by DAPT modification of recombinant FVIII (rFVIII), resulting in less frequent infusions can provide significant benefits and improve the quality of life of persons with haemophilia. To address these needs, a long-acting rFVIII was developed by covalently linking a single 60 kDa PEG molecule to one amino acid in rFVIII [16]. The 60 kDa PEG size was selected over smaller PEG molecules size of 12, 20 and 30 kDa, as it provided the best half-life prolongation,

as observed in preclinical studies. This PEGylated rFVIII molecule (BAY 94–9027, PLX3397 Bayer HealthCare, Berkeley, CA, USA) showed prolonged protection from bleeding, improved pharmacokinetics and no toxicity in preclinical studies [16]. Recently, a phase I study in humans using this PEG-60-rFVIII (BAY 94–9027) was completed, and showed that the drug was well tolerated, efficacious and had no serious adverse events (manuscript in preparation). A phase II/III clinical study with BAY 94–9027 is ongoing. The following review provides an assessment of the safety information of PEGylated proteins containing high molecular weight PEG (PEG 30 kDa and larger) with the focus on PEG-related safety for long-term (chronic) use in haemophilia. A review of literature of preclinical safety and toxicity, as well as clinical studies

of large PEG molecules using keywords [Medline keywords: haemophilia PEGylation (six articles), PEG preclinical safety (17), PEGylated protein in vivo review (33); Toxline keywords: PEGylated protein safety (49)] and publically available Summary Basis of Approval documents selleck inhibitor from the US Food and Drug Administration (FDA) and European Public Assessment Reports (EPAR) drug approval information from the European Medicinal Agency (EMA) was carried out searching for PEGylated proteins and PEG safety (accessed January 2012) [17, 18]. The search strategy was broad to minimize the possibility of overlooking articles relevant to high molecular weight (≥30 kDa) PEG. Studies that looked at currently available marketed high molecular PEG products were reviewed for chronic administration, side-effects and adverse event profiles with specific determination to see if the adverse events reported were due to PEG. To search for safety information on PEGylated coagulation factors, the following search terms and their combination were used: PEGylated FVII, VIII or IX drugs; and coagulation factors VII, VIII, or IX with PEGylation terms (Biomedical Core Database).

The pathogenesis of CF-associated liver disease (CFLD) is incompl

The pathogenesis of CF-associated liver disease (CFLD) is incompletely understood, with onset and progression difficult to predict and monitor. Current measures of liver function, Cobimetinib datasheet combined with ultrasound and clinical examination are insensitive and non-specific for detection of early liver disease and assessment of progressive fibrosis severity. Although biopsy remains the gold standard for diagnosis of CFLD, it is invasive and can be confounded by the focal nature of disease activity. Thus a sensitive, specific and non-invasive test is required to identify individuals at risk of developing

CFLD prior to the Y27632 advent of complications. Distinct circulating microRNA (miR) profiles have been identified in various adult chronic liver diseases. In this study we sought to quantify the expression of serum miRs in CFLD patients, CF patients without LD (CFnoLD) and non-CF pediatric controls. Methods: Serum was obtained with informed consent from 102 children (52 CFLD, 30 CFnoLD, 20 non-CF controls). RNA was extracted from 200 μL serum and subjected to Qiagen Human Serum miRNA Real-Time RT-PCR

Array, containing 84 miRs detectable in human serum. Identified candidate miRs (miR-122, miR-25 and miR-21) were validated by real-time RT-PCR using the Exiqon miRCURY LNA PCR system for biofluids. miR expression was normalised to miR-19b and

miR-93, determined by geNorm to be the most stable reference miRs in the array. Results: miR-122 was significantly upregulated in CFLD vs. both CFnoLD and Controls (KW ANOVA, P < 0.0001). Of interest, both miR-25 (KW ANOVA, P = 0.01) and miR-21 (KW ANOVA, P = 0.05) were significantly increased in CFnoLD vs. both CFLD and Controls. Using receiver-operator characteristic check details (ROC) curve analysis, liver disease in CF (i.e. CFLD vs. CFnoLD alone) was discriminated by both miR-122 (AUROC = 0.71, P = 0.002) and miR-25 (AUROC = 0.65, P = 0.026). However, combined logistic regression including all three miRs (−122, −25, −21) showed a highly significant result for the detection of liver disease in CF (AUROC = 0.78, P < 0.0001). Conclusions: This work provides the first evidence of changes to circulating miR levels in CFLD. We demonstrate the potential of miR-122, miR-25 and miR-21 as biomarkers for the early diagnosis of CFLD, perhaps in association with previously discovered discriminatory fibrosis biomarkers. The potential contribution of miRs in predicting disease severity and in the mechanisms of liver pathology in CF patients requires further evaluation.

Despite their abundance and widespread usage as proxy indicators

Despite their abundance and widespread usage as proxy indicators for environmental conditions, there is a lack of knowledge regarding the dinocyst wall chemical composition. It is likely that numerous factors, including phylogeny and life strategy, determine the cyst wall chemistry. However, the extent to which this composition varies based on inherent (phylogenetic) or variable (ecological) factors

has not been studied. To address this, we used micro-Fourier transform infrared spectroscopy to analyze nine cyst species produced by either phototrophic ABT-263 molecular weight or heterotrophic dinoflagellates from the extant orders Gonyaulacales, Gymnodiniales, and Peridiniales. Based on the presence of characteristic functional groups, two significantly different cyst wall compositions are observed that correspond to the dinoflagellate’s nutritional

strategy. The dinocyst wall compositions analyzed appeared carbohydrate-based, but the cyst wall produced by phototrophic dinoflagellates suggested a cellulose-like glucan, while heterotrophic forms produced a nitrogen-rich glycan. This constitutes the first empirical evidence nutritional strategy is related to different dinocyst wall chemistries. Our results indicated phylogeny was less important for predicting composition than the nutritional strategy of the dinoflagellate, suggesting potential buy Omipalisib for cyst wall chemistry to infer past nutritional strategies of extinct taxa preserved in the sedimentary record. “
“Tolerance to drought stress in soil crust microorganisms is essential for exploiting suitable organisms for restoring soil. In this study, the responses to drought stress of two drought-tolerant species, a

green alga and a cyanobacterium, were compared with those of two non-tolerant green algae. In response to drought stress, induced by treatment with polyethylene glycol, the intracellular proline levels increased and were associated with increases in malondialdehye, pigment contents, and enzyme activities such as superoxide dismutase (SOD) and peroxidase (POD). Our results suggest that tolerance to drought stress could be indicated by the intracellular check details levels of proline, SOD, and carotenoids. This study provides insights into the drought physiology of the photosynthetic microorganisms and suggests that Leptolyngbya boryana and Chlorella vulgaris are suitable pioneer organisms for soil restoration. Soil algae and cyanobacteria are usually the pioneer colonizers in bare soils. They form BSCs and exert crucial influences on the development of pedo-ecosystems (Moore 1998, Belnap 2003). Adaptive mechanisms that enhance tolerance to stress are required for BSCs to survive stressful conditions such as desiccation, extreme temperature, high incident solar radiation, and low nutrients.

There is no vaccine to prevent HCV infection and only a subset of

There is no vaccine to prevent HCV infection and only a subset of patients respond to antiviral therapy.1 HCV infection is a highly dynamic process, with a viral half-life of only a few hours and average daily virion production of estimated 1012 particles in a given individual. This high replicative activity together with the lack of a proofreading function of the viral polymerase leads to a high genetic variability of HCV.2 Approximately 30% of individuals spontaneously clear acute HCV infection. Clearance

of HCV infection has been associated with a strong Maraviroc price and sustained T-cell response targeting multiple HCV regions, as recently reviewed.3 Although HCV-specific memory T cells remain detectable for decades in patients with resolved HCV infection, they appear not to be sufficient to prevent HCV infection upon reexposure to the virus. However, selleck kinase inhibitor the reduced risk of developing persistent HCV infection upon viral reexposure in frequently exposed subjects indicates that the immune system can develop some degree of protective immunity against HCV.4-6 Thus, vaccine approaches that are capable of converting an evolving chronic infection into an acute self-limiting infection would have a substantial impact for protection from disease.7, 8 Experimental HCV infection in chimpanzees is currently the only established in vivo model for the

study of HCV infection. In contrast to humans, chimpanzees clear HCV infection more frequently (50%-60%),9 making it an attractive model to study immunological determinants involved in selleckchem HCV

clearance and protection. Several studies in chimpanzees demonstrated that protective immunity upon viral rechallenge with HCV of the same genotype and even with other genotypes is associated with a rapid and vigorous HCV-specific T-cell response and the induction of intrahepatic interferon gamma (IFN-γ).10-13 But other studies showed that chimpanzees are not consistently protected even upon homologous rechallenge and in the presence of primed T cells.14, 15 Many studies in HCV-infected humans supported the importance of T-cell response in viral clearance either during primary infection or reinfection (review3). However, these studies investigated the peripheral immune response and did not explore intrahepatic immune responses in a comprehensive manner. These findings indicate that the immunological determinants mediating protective immunity are quite complex and not completely understood, and studies of intrahepatic immune responses may be crucial to understand these protective determinants. To identify immunological determinants associated with protective immunity upon HCV reexposure, we performed an extensive analysis of the innate and adaptive immune responses following HCV rechallenge in two chimpanzees that had previously recovered from primary HCV-JFH1 infection.

Little is known of national utilization practices and outcomes wi

Little is known of national utilization practices and outcomes with ≥80y donors. Methods: Using UNOS registry data, all U.S. adult recipients of primary deceased donor LT from 2/05-1/12 were evaluated (n=36,318). Centers (n=132) were categorized based on the # of ≥80y livers transplanted: non- (n=95), low- (n=31, range: 1-7 grafts/center), and high-utilizers (n=6, range: 22-36 grafts/center). Regions (n=11) were categorized as low-, mid-, and high-MELD based on tertiles of median recipient LT-MELD. Cox models evaluated the effects of donor

age ≥80y on graft loss (death or re-LT). selleck chemicals Results: 244 ≥80y donor livers were transplanted. Donors ≥80y vs <80y differed by %female (63 vs 40%), %with diabetes (15 vs 11%) and/ or hypertension (73 vs 35%), %died of stroke (75 vs 42%), %donation

AT9283 research buy after cardiac death (0 vs 5%), and %distributed nationally (33 vs 6%) [p<0.01 for all], but not by cold ischemia time (6.7 vs 6.6 hours; p=0.41). Recipients of ≥80y vs <80y livers were older (median 60 vs 55y), more likely to be female (42 vs 32%), less likely to have HCV (11 vs 27%), and had lower median laboratory LT-MELD (17 vs 20) [p<0.01 for all], but were similar for %hepatocellular carcinoma (18 vs 23%; p=0.07). Only 37/132 (28%) centers transplanted ≥80y livers, but 174/244 (71%) of the ≥80y livers were transplanted by 6 centers (high-utilizers), accounting for 2-8% of each center's total transplant volume; 3, 2, and 1 centers were in high-, mid-, and low-MELD regions, respectively. The adjusted hazard ratio (aHR) for graft loss

of ≥80y livers was 1.15 (95% CI 0.93-1.43; p=0.20). Low- and high-utilizers did not differ in graft survival of ≥80y livers (aHR 1.88, 95% CI 0.85-4.13, p=0.12). Overall graft survival of ≥80y vs <80y livers was 88% vs 91% at 3 months learn more (p=0.07), 75% vs 79% at 1y (p=0.14), and 48% vs 47% at 3y after LT (p=0.67). Re-LT occurred in 7% and 5% recipients of ≥80y vs <80y livers (p=0.01); %re-LT for ≥80y graft recipients did not differ between low- and high-utilizers (7 vs 7%; p=0.97). Among ≥80y grafts that failed within 1y of LT, only recipient LT-MELD score predicted failure (OR 1.05 per MELD point, 95% CI 1.01-1.09; p=0.03). Conclusion: The vast majority of ≥80y donor livers are accepted and transplanted by only 6 U.S. LT centers. Graft survival with ≥80y livers was acceptable and did not vary by center experience with ≥80y donors. Codification of objective selection criteria may increase utilization of older donors while maintaining the currently observed post-LT outcomes. Disclosures: The following people have nothing to disclose: Suzanne R. Sharpton, Sandy Feng, Jennifer C.