Reciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism.

Agouti-related peptide (AgRP)-expressing and proopiomelanocortin (POMC)-expressing neurons reciprocally regulate food intake. Here, we combine non-interacting recombinases to simultaneously express functionally opposing chemogenetic receptors in AgRP and POMC neurons for comparing metabolic responses in male and female mice with simultaneous activation of AgRP and inhibition of POMC neurons with isolated activation of AgRP neurons or isolated inhibition of POMC neurons. We show that food intake is regulated by the additive effect of AgRP neuron activation and POMC neuron inhibition, while systemic insulin sensitivity and gluconeogenesis are differentially modulated by isolated-versus-simultaneous regulation of AgRP and POMC neurons. We identify a neurocircuit engaging Npy1R-expressing neurons in the paraventricular nucleus of the hypothalamus, where activated AgRP neurons and inhibited POMC neurons cooperate to promote food consumption and activate Th+ neurons in the nucleus tractus solitarii. Collectively, these results unveil how food intake is precisely regulated by the simultaneous bidirectional interplay between AgRP and POMC neurocircuits.

Textbook outcome in distal pancreatectomy: A multicenter study.

BACKGROUND: Textbook outcome is an interesting quality metrics tool. Information on textbook outcomes in distal pancreatectomy is very scarce. In this study we determined textbook outcome in a distal pancreatectomy multicenter database and propose a specific definition of textbook outcome-distal pancreatectomy that includes pancreatic fistula. METHODS: Retrospective multicenter observational study of distal pancreatectomy performed at 8 hepatopancreatobiliary surgery units from January 1, 2008, to December 31, 2018. The inclusion criteria were any scheduled distal pancreatectomy performed for any diagnosis and age > 18 years. Specific textbook outcome-distal pancreatectomy was defined as hospital stay P < 75, no Clavien-Dindo complications (≥ III), no hospital mortality, and no readmission recorded at 90 days, and the absence of pancreatic fistula (B/C). RESULTS: Of the 450 patients included, 262 (58.2%) obtained textbook outcomes. Prolonged stay was the parameter most frequently associated with failure to achieve textbook outcomes. The textbook outcome group presented the following results. Preoperative: lower American Society of Anesthesiologists score < III, a lower percentage of smokers, and less frequent tumor invasion of neighboring organs or vascular invasion; operative: major laparoscopic approach, and less resection of neighboring organs and less operative transfusion; postoperative: lower percentage of delayed gastric emptying and pancreatic fistula B/C, and diagnosis other an adenocarcinoma. In the multivariate study, the American Society of Anesthesiologists score > II, resection of neighboring organs, B/C pancreatic fistula, and delayed gastric emptying were associated with failure to achieve textbook outcomes. CONCLUSION: The textbook outcome rate in our 450 pancreaticoduodenectomies was 58.2%. In the multivariate analysis, the causes of failure to achieve textbook outcomes were American Society of Anesthesiologists score > II, resection of neighboring organs, pancreatic fistula B/C, and delayed gastric emptying. We believe that pancreatic fistula should be added to the specific definition of textbook outcome-distal pancreatectomy because it is the most frequent complication of this procedure.

CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice.

Dysregulation of hypothalamic ceramides has been associated with disrupted neuronal pathways in control of energy and glucose homeostasis. However, the specific ceramide species promoting neuronal lipotoxicity in obesity have remained obscure. Here, we find increased expression of the C16:0 ceramide-producing ceramide synthase (CerS)6 in cultured hypothalamic neurons exposed to palmitate in vitro and in the hypothalamus of obese mice. Conditional deletion of CerS6 in hypothalamic neurons attenuates high-fat diet (HFD)-dependent weight gain and improves glucose metabolism. Specifically, CerS6 deficiency in neurons expressing pro-opiomelanocortin (POMC) or steroidogenic factor 1 (SF-1) alters feeding behavior and alleviates the adverse metabolic effects of HFD feeding on insulin sensitivity and glucose tolerance. POMC-expressing cell-selective deletion of CerS6 prevents the diet-induced alterations of mitochondrial morphology and improves cellular leptin sensitivity. Our experiments reveal functions of CerS6-derived ceramides in hypothalamic lipotoxicity, altered mitochondrial dynamics, and ER/mitochondrial stress in the deregulation of food intake and glucose metabolism in obesity.

HypoMap-a unified single-cell gene expression atlas of the murine hypothalamus.

The hypothalamus plays a key role in coordinating fundamental body functions. Despite recent progress in single-cell technologies, a unified catalog and molecular characterization of the heterogeneous cell types and, specifically, neuronal subtypes in this brain region are still lacking. Here, we present an integrated reference atlas, 'HypoMap,' of the murine hypothalamus, consisting of 384,925 cells, with the ability to incorporate new additional experiments. We validate HypoMap by comparing data collected from Smart-Seq+Fluidigm C1 and bulk RNA sequencing of selected neuronal cell types with different degrees of cellular heterogeneity. Finally, via HypoMap, we identify classes of neurons expressing glucagon-like peptide-1 receptor (Glp1r) and prepronociceptin (Pnoc), and validate them using single-molecule in situ hybridization. Collectively, HypoMap provides a unified framework for the systematic functional annotation of murine hypothalamic cell types, and it can serve as an important platform to unravel the functional organization of hypothalamic neurocircuits and to identify druggable targets for treating metabolic disorders.

Pancreatic mucinous cystic neoplasms located in the distal pancreas: a multicenter study.

Background: Mucinous cysts of the pancreas (MCN) are infrequent, usually unilocular tumors which occur in postmenopausal women and are located in the pancreatic body/tail. The risk of malignancy is low. The objective is to define preoperative risk factors of malignancy in pancreatic MCN and to assess the feasibility of the laparoscopic approach. Methods: Retrospective multicenter observational study of prospectively recorded data regarding distal pancreatectomies was carried out at seven hepatopancreatobiliary (HPB) Units between 01/01/08 and 31/12/18 (the ERPANDIS Project). Results: Four hundred and forty-four distal pancreatectomies were recorded including 47 MCN (10.6%). Thirty-five were non-invasive tumors (74.5%). In all, 93% of patients were female, and 60% were ASA (American Society of Anaesthesiology) II. The mean preoperative size was 46 mm. Patients with invasive tumors were older (54 vs. 63 years). Invasive tumors were larger (6 vs. 4 cm), although the difference was not significant (P=0.287). Sixty percent was operated via laparoscopic approach, which was used in 74.6% of non-invasive tumors and in 16.7% of the invasive ones. The spleen was not preserved in 93.6% of the patients. R0 resection was obtained in all patients. Two patients with invasive tumors died. Conclusions: In our surgical series of MCN, patients with malignancy were older and presented larger tumors, although the difference was not statistically significant. Laparoscopy is a safe and feasible approach for MCN. Prospective studies are now needed to define risk factors that can guide the decision whether to administer conservative treatment or to operate.

Un caso de síndrome de crouzon con sintomatología psiquiátrica / A case of Crouzon syndrome with psychiatric symptoms

El síndrome de Crouzon es un trastornoautosómico dominante caracterizado por craneosinostosis (cierre prenatal de una o varias suturas craneales) que provoca alteraciones secundarias de los huesos craneales y de la estructura facial. Las características más frecuentes incluyen deformidadesde cráneo y cara: proptosis ocular, exoftalmos y estrabismo divergente, nariz en forma de pico de loro, labio superior corto, maxilar hipoplásico y prognatismo mandibular relativo. La presión intracraneal enalgunos casos puede producir trastornos neurológicos y discapacidad intelectual.Realizamos una breve revisión del concepto y planteamos un caso clínico quepresenta graves alteraciones de conducta con agresividad y escasa respuesta terapéutica. (AU)

Crouzon syndrome is an autosomal dominant disorder characterized by craniosynostosis (prenatal closure of one or morecranial sutures) that causes secondary alterations of the cranial bones and facial structure. The most frequent features include skull and facial deformities: ocular proptosis, divergent exophthalmos and strabismus,parrot beak-shaped nose, short upper lip, hypoplastic maxilla, and relative mandibular prognathism. Intracranial pressure in some cases can cause neurological disorders andintellectual disability.We carry out a brief review of the concept and we present a clinical case that presents serious behavior alterations with aggressiveness and little therapeutic response. (AU)

Distal pancreatectomy with multivisceral resection: A retrospective multicenter study - Case series.

BACKGROUND: Multivisceral resection (MVR) is sometimes necessary to achieve disease-free margins in cancer surgery. In certain patients with pancreatic tumors that invade neighboring organs these must be removed to perform an appropriate oncological surgery. In addition, there is an increasing need to perform resections of other organs like liver not directly invaded by the tumor but which require synchronous removal. The results of MVR in pancreatic surgery are controversial. MATERIAL AND METHODS: A distal pancreatectomy retrospective multicenter observational study using prospectively compiled data carried out at seven HPB Units. The period study was January 2008 to December 2018. We excluded DP with celiac trunk resection. RESULTS: 435 DP were performed. In 62 (14.25%) an extra organ was resected (82 organs). Comparison of the preoperative data of MVR and non-MVR patients showed that patients with MVR had lower BMI, higher ASA and larger tumor size. In the MVR group, the approach was mostly laparotomic and spleen preservation was performed only in 8% of the cases, Blood loss and the percentage of intraoperative transfusion were higher in MVR group. Major morbidity rates (Clavien > IIIa) and mortality (0.8vs.4.8%) were higher in the MVR group. Pancreatic fistula rates were practically the same in both groups. Mean hospital stay was twice as long in the MVR group and the readmission rate was higher in the MVR group. Histology study confirmed a much higher rate of malignant tumors in MVR group. CONCLUSIONS: In order to obtain free margins or treat pathologies in several organs we think that DP + MVR is a feasible technique in selected patients; the results obtained are not as good as those of DP without MVR but are acceptable nonetheless. CLINICALTRIALS. GOV IDENTIFIER: NCT04317352.

GLP-1 Receptor Signaling in Astrocytes Regulates Fatty Acid Oxidation, Mitochondrial Integrity, and Function.

Astrocytes represent central regulators of brain glucose metabolism and neuronal function. They have recently been shown to adapt their function in response to alterations in nutritional state through responding to the energy state-sensing hormones leptin and insulin. Here, we demonstrate that glucagon-like peptide (GLP)-1 inhibits glucose uptake and promotes ß-oxidation in cultured astrocytes. Conversely, postnatal GLP-1 receptor (GLP-1R) deletion in glial fibrillary acidic protein (GFAP)-expressing astrocytes impairs astrocyte mitochondrial integrity and activates an integrated stress response with enhanced fibroblast growth factor (FGF)21 production and increased brain glucose uptake. Accordingly, central neutralization of FGF21 or astrocyte-specific FGF21 inactivation abrogates the improvements in glucose tolerance and learning in mice lacking GLP-1R expression in astrocytes. Collectively, these experiments reveal a role for astrocyte GLP-1R signaling in maintaining mitochondrial integrity, and lack of GLP-1R signaling mounts an adaptive stress response resulting in an improvement of systemic glucose homeostasis and memory formation.

Hypomorphic Expression of Pitx3 Disrupts Circadian Clocks and Prevents Metabolic Entrainment of Energy Expenditure.

Daily adaptation of metabolic activity to light-dark cycles to maintain homeostasis is controlled by hypothalamic nuclei receiving information from the retina and from nutritional inputs that vary according to feeding cycles. We show that selective hypomorphic expression of the transcription factor gene Pitx3 prevents light-dependent entrainment of the central pacemaker in the suprachiasmatic nucleus. This translates into altered behavioral and metabolic outputs affecting locomotor activity, feeding patterns, energy expenditure, and corticosterone secretion that correlate with dysfunctional expression of clock genes in the ventromedial hypothalamus, liver, and brown adipose tissue. Metabolic entrainment by time-restricted feeding restores clock function in the liver and brown adipose tissue but not in the ventromedial hypothalamus and, remarkably, fails to synchronize energy expenditure and locomotor and hormonal outputs. Thus, our study reveals a central role of the priming of the suprachiasmatic nucleus with retinal innervation in the hypothalamic regulation of cyclic metabolic homeostasis.

Temporary Intraoperative Porto-Caval Shunts in Piggy-Back Liver Transplantation Reduce Intraoperative Blood Loss and Improve Postoperative Transaminases and Renal Function: A Meta-Analysis.

BACKGROUND: The value of temporary intraoperative porto-caval shunts (TPCS) in cava-sparing liver transplantation is discussed controversially. Aim of this meta-analysis was to analyze the impact of temporary intraoperative porto-caval shunts on liver injury, primary non-function, time of surgery, transfusion of blood products and length of hospital stay in cava-sparing liver transplantation. METHODS: A systematic search of MEDLINE/PubMed, EMBASE and PsycINFO retrieved a total of 909 articles, of which six articles were included. The combined effect size and 95 % confidence interval were calculated for each outcome by applying the inverse variance weighting method. Tests for heterogeneity (I 2) were also utilized. RESULTS: Usage of a TPCS was associated with significantly decreased AST values, significantly fewer transfusions of packed red blood cells and improved postoperative renal function. There were no statistically significant differences in primary graft non-function, length of hospital stay or duration of surgery. CONCLUSION: This meta-analysis found that temporary intraoperative porto-caval shunts in cava-sparing liver transplantation reduce blood loss as well as hepatic injury and enhance postoperative renal function without prolonging operative time. Randomized controlled trials investigating the use of temporary intraoperative porto-caval shunts are needed to confirm these findings.

Recurrent hepatitis C virus infection and outcome after living-donor liver transplant.

OBJECTIVES: In living-donor liver transplant recipients with hepatitis C virus infection, outcomes of recurrent hepatitis C virus infection and fibrosis progression are not well documented. We evaluated fibrosis progression, response to pegylated interferon treatment, and long-term graft survival in living-donor liver transplant recipients who had hepatitis C virus infection. MATERIALS AND METHODS: In 48 transplant recipients, including 29 recipients who had follow-up liver biopsy ≥ 6 months after transplant, histology and clinical courses were reviewed. Outcomes were evaluated for patients grouped into slow and rapid fibrosis groups. Treatment with pegylated interferon and ribavirin was assessed in 18 patients. RESULTS: Clinical features were similar between recipients with slow or rapid fibrosis. The time interval from transplant to recurrence of hepatitis C virus infection was significantly shorter in the recipients with rapid fibrosis. Recipients with rapid fibrosis had significantly greater confluent necrosis, acidophil bodies, and fibrosis score than recipients with slow fibrosis. Graft survival rates were similar between patients with slow or rapid fibrosis. Cumulative proportion of long-term graft survival was 60% at 7 years after transplant. Sustained virologic response was noted in 5 of 18 patients (28%) who received pegylated interferon and ribavirin. CONCLUSIONS: In recipients of living-donor liver transplant with early recurrence of hepatitis C have worse fibrosis progression but graft survival was not affected. Therapy with pegylated interferon and ribavirin achieved sustained virologic response only in a small proportion of the patients.

Granulation response and partial wound closure predict healing in clinical trials on advanced diabetes foot ulcers treated with recombinant human epidermal growth factor.

OBJECTIVE: To determine if partial wound closure surrogate markers proposed for neuropathic, small diabetic foot ulcers (DFUs) can be extended to advanced lesions and if the development of granulation tissue can be used to predict complete healing. RESEARCH DESIGN AND METHODS: Data from two multicenter, double-blind, randomized clinical trials (one of them placebo controlled) that used intralesional recombinant human epidermal growth factor (rhEGF) to promote granulation and healing were used. For confirmation in a larger sample from common clinical practice, the results of an active postmarketing surveillance of rhEGF treatment of DFUs in 60 healthcare units was included. The surrogates evaluated were percent area change, log healing rate, ratio of log areas, and percent of granulation tissue covering the wound area. The tests used were surrogate final end point correlation, receiver operating characteristic curves to discriminate healers from nonhealers, validation tests using logistic regression models, and the proportion-mediated estimation. RESULTS: Two weeks >50% granulation, end of treatment >75% granulation, and 16.1% area change showed significant predictive value (>70% correct classification) for final wound closure. The granulation-based variables fulfilled the criterion that the effect of rhEGF treatment on wound closure was mediated by the surrogate. CONCLUSIONS: This work provides the first evidence for the use of granulation tissue development as a predictor of wound healing in advanced DFUs. These results can be useful for clinical trial design, particularly during the exploratory phase of new products.

Mortality associated with carbapenem-resistant Klebsiella pneumoniae infections in liver transplant recipients.

Resistant bacterial infections are important causes of morbidity and mortality after liver transplantation (LT). This was a retrospective cohort study evaluating the outcomes associated with carbapenem-resistant Klebsiella pneumoniae (CRKP) infections after LT. In a 2005-2006 cohort of 175 consecutive LT recipients, 91 infection episodes were observed in 61 patients (35%). The mortality rate 1 year after LT was 18% (32/175). Enterococcus (43%) and Klebsiella species (37%) were the most frequently isolated bacteria. CRKP infections occurred in 14 patients, and 10 of these patients (71%) died. Seven of these deaths occurred within 30 days of the CRKP infection. The median time to the onset of CRKP infections was 12 days (range = 1-126 days) after LT. The survival rate was significantly lower for patients with a CRKP infection versus patients without a CRKP infection (29% versus 86%, log-rank P < 0.001). In a multivariate analysis, the only pre-LT and post-LT clinical variables significantly associated with death were a Model for End-Stage Liver Disease score ≥ 30 (hazard ratio = 3.4, P = 0.04) and a post-LT CRKP infection (hazard ratio = 4.9, P = 0.007). In conclusion, the outcomes associated with CRKP infections in LT recipients are poor. Because the optimal treatment strategies for CRKP infections remain undefined, improved preventive strategies are needed to curtail the devastating impact of CRKP in LT recipients.

Liver transplantation is possible in some patients with liver metastasis of colon cancer.

Liver metastases from colorectal cancer are an absolute contraindication for liver transplantation. Aggressive therapy with liver resection and local chemotherapy in selected patients may be able to provide long-term cure. Given the risks of tumor recurrence, whether patients with post chemotherapy complications leading to liver failure should be offered transplantation is a challenging question in an era of limited organ availability. Herein we have presented 2 cases of liver transplantation performed in patients with colorectal cancer metastases treated with liver resection followed by hepatic artery infusion chemotherapy leading to development of sclerosing cholangitis and eventual liver failure. This report demonstrates that liver transplantation may be an option in selected patients with colorectal cancer liver metastases that have been well treated.

Clinical characterization of patients developing histologically-proven fibrosing cholestatic hepatitis C post-liver transplantation.

AIM: Fibrosing cholestatic hepatitis C (FCH) post-liver transplantation (LT) is an uncommon disorder with extremely poor outcome. Using stringent histological criteria, we sought to identify cases of FCH to better characterize its incidence, clinical features and outcomes. METHODS: From January 1991 to December 2007, 973 LT for hepatitis C virus (HCV) were performed at our center. Using the pathology database, 51 cases with a provisional diagnosis of FCH were identified. FCH was diagnosed histologically by cholestasis accompanied by thin periportal fibrous septa, ductular reaction and mild inflammation. RESULTS: FCH was reconfirmed in 24 recipients; seven had concurrent biliary problems. Twenty-seven cases were excluded; biopsy was unavailable in nine cases, 15 did not meet the histological criteria of FCH and three had missing clinical information. All received deceased donors at a mean age of 64.4 years (15/17 aged >50 years). Mean time from LT to FCH was 7.6 months with 16 of 17 diagnosed within 1 year of LT. At diagnosis, mean viral load was 14.4 million IU/mL, bilirubin 16.2 mg/dL, aspartate aminotransferase 262 IU/mL, alanine aminotransferase 192 IU/mL and alkaline phosphatase 299 IU/mL. All 17 patients died or required re-LT a mean of 7.8 months after the FCH diagnosis. CONCLUSION: FCH occurs infrequently and is typified by hyperbilirubinemia, donor age of more than 50 years, extremely high HCV RNA and specific histological changes occurring within the first several months post-LT with extremely poor patient and graft survival. Histology alone is not reliable for the diagnosis of FCH, especially in the setting of recurrent HCV with concurrent biliary problems.

The beneficial impact of temporary porto-caval shunt in orthotopic liver transplantation: a single center analysis.

The use of temporary porto-caval shunt (TPCS) has been shown to improve hemodynamic stability and renal function in patients undergoing orthotopic liver transplantation (OLT). We evaluated the impact of TPCS in OLT and analyzed the differences according to model for end-stage liver disease (MELD), donor risk index (DRI) and D-MELD. This is a retrospective single-center analysis of 148 consecutive OLT. Fifty-eight OLT were performed using TPCS and 90 without TPCS. Donor and recipient data with pre-OLT, intraoperative and postoperative variables were reviewed. Overall graft survival was 89.9% at 3 months and 81.7% at 1 year. Graft survival at 3 months and 1 year was 93.1% and 79.2%, respectively, in TPCS group versus 85.6% and 82.2%, respectively, in non-TPCS group (P = NS). Intraoperative packed red blood cells requirement was lower in TPCS group (7.5 ± 5.8 vs. 12.2 ± 14.2, P = 0.006) and non-TPCS group required higher intraoperative total dose of phenylephrine (16% vs. 28%, P = 0.04). TPCS group had lower 30-day postoperative mortality (1.7% vs. 10%, P = 0.04), no difference was observed at 90 days. Graft survival was lower in patients with high DRI; in this group graft loss was higher at 1 month (25% vs. 4.3%, P = 0.005) and 3 months (25% vs. 4.3%, P = 0.005) when TPCS was not used. TPCS improves perioperative outcome, this being more evident when high-risk grafts are placed into high-risk patients.

Factors associated with persistent thrombocytopenia after liver transplantation.

BACKGROUND: Thrombocytopenia typically resolves with resolution of portal hypertension after liver transplantation (LT) but persists in some patients. Identifying risk factors associated with persistent post- LT thrombocytopenia may provide important information about its pathogenesis. METHODS: Cirrhotic adults with platelet levels of <150,000 mu/L at the time of LT and followed at least 1 year were studied. A retrospective analysis of lab values, radiologic spleen index (SI), and donor data using nonparametric methods was performed to characterize patients having persistent thrombocytopenia, defined as persistently low platelet levels at 3 and 12 months after LT. RESULTS: One hundred patients were studied: mean age 55 y (range 23-75 y); platelet count at LT 62,000/microL (range 14,000- 148,000/microL; mean total bilirubin 2.6 mg/dL; mean Mayo end-stage liver disease score 29; SI 1,476 (range 347-4,843 mL; normal 120-480 mL). Platelet count at 3 and 12 months after LT correlated with SI (r = -0.41 and -0.54; P < .001). Fifty-seven patients had persistent thrombocytopenia. Compared with patients whose platelet levels normalized by month 3 or 12, they had higher SI and lower platelet count before LT (P < .001). The SI and platelet levels at the time of LT were independent predictive factors for platelet levels at 3 and 12 months after LT (P < .001). CONCLUSIONS: High SI and low platelet count at the time of LT are associated with persistent thrombocytopenia after LT. They are also independent predictive factors of platelet levels at 3 and 12 months after LT. This suggests that patients may have persistent thrombocytopenia after LT owing to persistence of some degree of hypersplenism and incomplete resolution of splenomegaly.

Nevirapine-induced stevens johnson-syndrome and fulminant hepatic failure requiring liver transplantation.

We describe a case of nevirapine-induced Stevens-Johnson Syndrome (SJS) and fulminant hepatic failure (FHF) requiring liver transplantation. Five weeks prior to admission, a 57-year-old female with HIV infection had been switched to a nevirapine-based regimen of highly active antiretroviral therapy (HAART) with a CD4 cell count of 695/mm(3). Examination of the explanted native liver at initial transplantation revealed massive hepatic necrosis consistent with drug-induced liver injury. Primary graft nonfunction complicated the early postoperative course and liver retransplantation was required. On follow-up 2 years later, she remains in good health with an undetectable viral load on an efavirenz-based regimen of HAART. To our knowledge, this is the first report of successful liver transplantation following SJS and FHF.

Improved outcomes in pediatric liver transplantation for acute liver failure.

UNLABELLED: OLT is a life-saving option for ALF. AIM: To evaluate our outcomes in pediatric OLT for ALF. METHODS: Retrospective review of our data between 1992 and 2007. RESULTS: Of 142 children with ALF, 126 were listed, of which 40 spontaneously improved, nine died, and 77 underwent OLT (median waiting time four days). Fifty-three children received deceased donor grafts (34 whole and 19 split grafts), and there were 24 living donor grafts. The one- and five-yr patient survival was 87% and 80%, and graft survival 83% and 79%, respectively. Thirteen patients died after OLT, and there were nine retransplants in seven patients. Patient weight, length of stay, creatinine, and infection were significantly associated with death; increased weight and black ethnicity were associated with graft loss on univariate analysis, but not on multivariate analysis. There were no significant differences in patient survival (one and five yr), graft loss, or other complications between the groups. CONCLUSION: We report the largest single-center study of OLT in pediatric ALF, demonstrating no difference in outcomes between different graft types. Our liberal use of segmental grafts may allow earlier OLT in this high-risk cohort and contribute to our excellent outcomes.