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Les derniers abstracts de la revue Liver Transplantation :


    Date de mise en ligne : Mardi 19 septembre 2017
    Dana Tedesco, Arash Grakoui
    Environmental peer pressure: CD4+ T cell help in tolerance and transplantation
    The liver participates in a multitude of metabolic functions that are critical for sustaining human life. Despite constant encounters with antigenic‐rich intestinal blood, oxidative stress and metabolic intermediates, there is no appreciable immune response. Interestingly, patients undergoing orthotopic liver transplantation benefit from a high rate of graft acceptance in comparison to other solid organ transplant recipients. In fact, co‐transplantation of a donor liver in tandem with a rejection‐prone graft increases the likelihood of graft acceptance. A variety of players may account for this phenomenon including the interaction of intrahepatic antigen presenting cells with CD4+ T cells and the preferential induction of Foxp3 expression on CD4+ T cells following injurious stimuli. Ineffective insult management can cause chronic liver disease, which manifests systemically as: antibody mediated disorders, ineffective antiviral and antibacterial immunity, and gastrointestinal disorders. These sequelae share the requirement of CD4+ T cell help to coordinate aberrant immune responses. In this review, we will focus on CD4+ T cell help due to the shared requirements in hepatic tolerance and coordination of extrahepatic immune responses. Overall, intrahepatic deviations from steady state can have deleterious systemic immune outcomes, and highlight the liver's remarkable capacity to maintain a balance between tolerance and inflammatory response while simultaneously being inundated with a panoply of antigenic stimuli. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Mardi 19 septembre 2017
    Burcin Ekser, Richard S. Mangus, Chandrashekhar A. Kubal, John A. Powelson, Jonathan A. Fridell, William C. Goggins
    Excellent outcomes in combined liver‐kidney transplantation: Impact of KDPI and delayed kidney transplantation
    The positive impact of delayed kidney transplantation (KT) on patient survival for combined liver‐KT (CLKT) has already been demonstrated by our group. The purpose of this study is to identify whether the quality of the kidneys (based on KDPI) or the delayed approach KT contributes to improved patient survival. 130 CLKT were performed between 2002‐2015; 69 with simultaneous KT (Group S) and 61 with delayed KT (Group D) (performed as a second operation with a mean cold ischemia time [CIT] of 50±15h). All patients were categorized according to the KDPI score; 1‐33%, 34‐66%, and 67‐99%. Recipient and donor characteristics were comparable within Groups S and D. Transplant outcomes were comparable within Groups S and D, including liver and kidney CIT, warm ischemia time, and delayed graft function. Lower KDPI kidneys (<34%) were associated with increased patient survival in both groups. Combination of delayed KT and KDPI 1‐33% resulted in 100% patient survival at 3‐years. These results support that delayed KT in CLKT improves patient survival. The combination of delayed KT and low KDPI offers excellent patient survival up to 3‐years. Improved outcomes in the delayed KT group including high KDPI kidneys supports expansion of the donor pool with the use of more ECD and DCD kidneys. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Mardi 19 septembre 2017
    Talia B. Baker, Michael A. Zimmerman, Nathan P. Goodrich, Benjamin Samstein, Elizabeth A. Pomfret, James J. Pomposelli, Brenda W. Gillespie, Carl L. Berg, Jean C. Emond, Robert M. Merion
    Biliary Reconstructive techniques and associated anatomic variants in adult living donor liver transplants: The A2ALL experience
    Introduction: Living donor liver transplantation (LDLT) is a technically demanding endeavor, requiring command of the complex anatomy of partial liver grafts. We examined the influence of anatomic variation and reconstruction technique on surgical outcomes and graft survival in the nine‐center A2ALL Study. Methods: Data from 272 adult LDLT recipients (2011‐2015) included details on anatomic characteristics and types of intraoperative biliary reconstruction. Associations were tested between reconstruction technique and complications, which included first biliary complication ([BC]; leak, stricture, or biloma) and first vascular complication (hepatic artery thrombosis [HAT] or portal vein thrombosis [PVT]). Time to patient death, graft failure, and complications were estimated using Kaplan‐Meier curves and tested with log‐rank tests. Results: Median post‐transplant follow‐up was 1.2 years. Associations were found between the type of biliary reconstruction and the incidence of vascular complication (p=0.034) and BC (p=0.053). Recipients with Roux‐en‐Y hepatico‐jejunostomy had the highest probability of vascular complication. Recipients with biliary reconstruction involving the use of high biliary radicals on the recipient duct had the highest likelihood of developing BC (56% by one year) compared to duct‐to‐duct (42% by one year). Conclusion: The varied surgical approaches in the A2ALL centers offer a novel opportunity to compare disparate LDLT approaches. The choice to use higher biliary radicals on the recipient duct for reconstruction was associated with more BC, possibly secondary to devascularization and ischemia. The use of Roux‐en‐Y biliary reconstruction was associated with vascular complications (HAT and PVT). These results can be used to guide biliary reconstruction decisions in the setting of anatomic variants and inform further improvements in LDLT reconstructions. Ultimately, this information may contribute to a lower incidence of technical complications after LDLT. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Samedi 16 septembre 2017
    Manhal Izzy, Kymberly D Watt
    The Reality of De Novo Malignancy: Sadly, Not Fake News
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    Date de mise en ligne : Samedi 16 septembre 2017
    María Dolores Ayllón, Rubén Ciria, Manuel Cruz‐Ramírez, María Pérez‐Ortiz, Roberto Valente, John O'Grady, Manuel de la Mata, César Hervás‐Martínez, Nigel D. Heaton, Javier Briceño
    Validation of artificial neural networks as a methodology for donor‐recipient matching for liver transplantation
    Background: In 2014, we reported a model for Donor‐Recipient matching (D‐R) in liver transplantation (LT) based on artificial‐neural‐networks (ANN) from a Spanish multicentre study (MADR‐E: Model for Allocation of Donor and Recipient in España). The aim is to test the ANN‐based methodology in a different European‐healthcare system in order to validate it. Methods: An ANN model was designed using a cohort of patients from King's College Hospital (KCH) (N=822). The ANN was trained and tested using KCH pairs for both 3‐ and 12‐months survival models. Endpoints were probability of graft survival (CCR) and non‐survival (MS). The final model is a rule‐based‐system for facilitating the decision about the most appropriate D‐R matching. Results: Models designed for KCH had excellent prediction capabilities for both 3‐months (CCR‐AUC=0.94; MS‐AUC=0.94) and 12‐months (CCR‐AUC=0.78; MS‐AUC=0.82), almost 15% higher than the best obtained by other known scores such as MELD and BAR. Moreover, these results improve the previously reported ones in the multicentric MADR‐E database. Conclusions: The use of ANN for D‐R matching in LT in other healthcare systems achieved excellent prediction capabilities supporting the validation of these tools. It should be considered as the most advanced, objective and useful tool to date for the management of waiting lists. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Vendredi 15 septembre 2017
    Jordan A Kohler, Flor M Munoz, John A Goss, Tamir A Miloh
    Viral Upper Respiratory Infection at Pediatric Liver Transplant is Associated with Hepatic Artery Thrombosis
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    Date de mise en ligne : Vendredi 08 septembre 2017
    Xijiao Liu, Hanyu Jiang, Jie Chen, You Zhou, Zixing Huang, Bin Song
    Gadoxetic acid‐enhanced MRI outperformed MDCT in diagnosing small hepatocellular carcinoma: A meta‐analysis
    Early detection of small hepatocellular carcinoma (HCC) lesions can improve long‐term patient survival. A systematic review and meta‐analysis of the diagnostic performance of gadoxetic acid disodium‐enhanced magnetic resonance imaging (Gd‐EOB‐DTPA‐enhanced MRI) and multidetector computed tomography (MDCT) was performed in diagnosing small HCCs measuring up to 2 cm(≤2cm). Two investigators searched multiple databases for studies in which the performances of either Gd‐EOB‐DTPA‐enhanced MRI or MDCT were reported with sufficient data to construct 2 × 2 contingency tables for diagnosing HCCs up to 2 cm on a per‐lesion or per‐patient level. Diagnostic performances were quantitatively pooled by a bivariate random‐effect model with further meta‐regression and subgroup analyses. Twenty‐seven studies (fourteen on Gd‐EOB‐DTPA‐enhanced MRI, nine on MDCT and four on both) were included, enrolling a total of 1735 patients on Gd‐EOB‐DTPA‐enhanced MRI and 1781 patients on MDCT. Gd‐EOB‐DTPA‐enhanced MRI demonstrated significantly higher overall sensitivity than did MDCT (0.96 vs 0.65, p<0.01), without substantial loss of specificity (0.98 vs 0.94, p>0.05). Area under the summary receiver operating characteristic curve was 0.9712 with Gd‐EOB‐DTPA‐enhanced MRI and 0.8538 with MDCT. Regarding Gd‐EOB‐DTPA‐enhanced MRI, sensitivity was significantly higher for studies from non‐Asian countries than Asian countries(0.96 vs 0.93, p<0.01), for retrospective studies than prospective studies(0.95 vs 0.91, p<0.01), and for those with Gd‐EOB‐DTPA injection rate≥1.5ml/s than that of<1.5ml/s (0.97 vs 0.90, p<0.01). Conclusions: Gd‐EOB‐DTPA‐enhanced MRI demonstrated higher sensitivity and overall diagnostic accuracy than MDCT, and thus should be the preferred imaging modality for diagnosing small HCCs measuring up to 2 cm. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Vendredi 08 septembre 2017
    Andrea Schlegel, Irene Scalera, M. Thamara, P.R. Perera, Marit Kalisvaart, Hynek Mergental, Darius F. Mirza, John Isaac, Paolo Muiesan
    Impact of donor age in donation after cardiac death liver transplantation: Is the cut‐off “60” still of relevance?
    Background Advanced donor age has been identified as risk factor, when combined with donor warm ischemia, e.g. in donation after circulatory death (DCD). In several countries DCD livers, older than 60 years are not considered suitable due to concerns related to poor graft function and development of ischaemic cholangiopathy. We evaluate in this study outcome after DCD liver transplantation using grafts from donors older than 60 years. Methodology We analysed outcome after DCD liver transplantation (n=315), comparing donors >60 years (n=93) and donors ≤60 years (n=222) from our centre between 2005 and 2015. Endpoints included graft function and complications, patient and graft survival. Multivariate risk analysis was performed to define further key factors that predicted inferior outcome. Results Donor age at the cut‐off 60 years failed to stratify patient and graft survival. The rate of vascular, biliary and overall complications was comparably low in both cohorts and the median CCI was 42,7 points, independent from the donor age. Secondly, donor BMI above a threshold of 25 kg/m2 significantly impacted on graft and patient survival, at any donor age, while donor warm and cold ischemia times were not predictive for graft loss. Conclusion Older DCD donors can be successfully used for liver transplantation with good long‐term outcomes, when further risk factors are limited. Additional risk is transmitted by an increased donor BMI, regardless of donor age. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Vendredi 08 septembre 2017
    Eung Chang Lee, Seong Hoon Kim, Jae Ryong Shim, Sang‐Jae Park
    Small‐for‐size grafts increase recurrence of hepatocellular carcinoma in liver transplantation beyond Milan criteria
    BACKGROUND: Living donor liver transplantation (LDLT) has been reported to have high rates of hepatocellular carcinoma (HCC) recurrence compared to deceased donor liver transplant (DDLT). This has been assumed to be due to the frequent use of small‐for‐size grafts (SFSG) in LDLT rather than DDLT, but the relationship between graft size and prognosis remains controversial. This study aimed to clarify the effect of SFSG on the oncologic outcomes of patients with HCC who underwent LDLT. METHODS: Between January 2005 and December 2015, 597 consecutive patients underwent LDLT. Among these patients, those with HCC who underwent LDLT were randomly matched to 1 (graft‐to‐recipient body weight ratio [GRWR] <0.8%): 3 (GRWR≥0.8%) ratio according to propensity score. HCC recurrence and patient survival were analyzed using the Kaplan‐Meier method and log‐rank test. In addition, stratified subgroup analysis based on the Milan criteria was performed. SFSG was defined as a GRWR<0.8%. RESULTS: Using propensity score matching, 82 patients with GRWR<0.8% and 246 patients with GRWR≥0.8% were selected. For patients with HCC within the Milan criteria, no significant difference of HCC recurrence (P=0.82) and patient survival (P=0.95) was found based on GRWR. However, for patients with HCC beyond the Milan criteria, 1‐, 3‐, and 5‐year recurrence free survival rates were 52.4%, 49.3%, and 49.3%, respectively, for patients with GRWR<0.8%, and 76.5%, 68.3%, and 64.3%, respectively, for patients with GRWR≥0.8% (P=0.049). The former group exhibited poor patient survival rates (P=0.047). CONCLUSIONS: For patients with HCC within the Milan criteria, no significant difference in oncologic outcomes was found based on liver graft size. However, among the patients with HCC beyond the Milan criteria, SFSG recipients showed poor oncologic outcomes. Since extended criteria are frequently used in LDLT for HCC, recipients' prognosis can be improved if liver grafts of appropriate size are carefully selected during donor selection. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Vendredi 08 septembre 2017
    Chathur Acharya, James B Wade, Andrew Fagan, Melanie White, Edith Gavis, Dinesh Ganapathy, HoChong Gilles, Douglas M Heuman, Jasmohan S Bajaj
    Overt Hepatic Encephalopathy impairs learning on the Encephalapp Stroop which is Reversible after Liver Transplant
    After an initial exposure, subjects can develop test‐taking/learning strategies called the “test sophistication effect. Cirrhotics wth prior overt hepatic encephalopathy (OHE) could have persistent learning impairments. Aim: To define learning/test‐sophistication on EncephalApp (downloadable Application) in OHE patients compared to no‐OHE patients and controls cross‐sectionally and longitudinally. Methods: The EncephalApp Stroop App consists of 2 sections; the easier “Off” run assesses psychomotor speed while the difficult “On” run assesses cognitive flexibility. Cross‐sectional Analysis: Cirrhotic outpatients with/without controlled OHE and healthy controls underwent EncephalApp testing, which requires 5 “off” and 5 “on” runs. We studied the difference in time required between completing trial 1 compared with trial 5 (delta 1‐5) in the both the “On” and “Off” runs in controls, all cirrhotics; and between prior OHE/no‐OHE cirrhotics. Longitudinal Analyses: Two groups of cirrhotics were studied; one was administered EncephalApp, ≥ 2 weeks apart and the second before, and 6 months post‐liver transplantation. Results: 89 controls and 230 cirrhotics (85 prior OHE, MELD 11) with similar age (64 vs 61, p=0.9) were included. Cirrhotic patients had impaired EncephalApp total times and impaired learning on the On runs compared to controls. OHE patients had worse EncephalApp times and learning with the On runs compared to no‐OHE patients, which persisted in the longitudinal cohort. No differences in learning were seen in the Off runs. After transplant there was restoration of learning capability with the On runs in the OHE patients. Conclusion: Cognitive flexibility tested by the EncephalApp On runs improves over time in healthy controls and no‐OHE but not prior OHE. Psychomotor speed remains similar over time. The learning Impairment manifested by cirrhotics with OHE is restored post‐transplant. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Lundi 28 aot 2017
    Charles C. Vining, Brett L. Ecker, Peter L. Abt, Kim M. Olthoff
    DCD in the HCC Patient: Same Indication?
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    Date de mise en ligne : Lundi 28 aot 2017
    Sezai Yilmaz
    Reply ‐ Reconstruction of anomalous portal venous branching in right lobe living donor liver transplantation: Malatya approach
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    Date de mise en ligne : Lundi 28 aot 2017
    James F. Trotter
    Controversies in Liver Transplantation: A New Series for the Journal
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    Date de mise en ligne : Lundi 28 aot 2017
    Kimberly Brown
    Maximizing Donors with Viral hepatitis in the Current Era
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    Date de mise en ligne : Lundi 28 aot 2017
    Michael R. Lucey
    Maximizing Allograft Function
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    Date de mise en ligne : Jeudi 24 aot 2017
    Joel P Wedd
    MELD Exceptions: A Common Problem
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    Date de mise en ligne : Jeudi 24 aot 2017
    Elizabeth C. Verna
    Vaccination to Prevent De Novo Hepatitis B: Are There Patients Who Don't Need Antiviral Prophylaxis?
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    Date de mise en ligne : Jeudi 17 aot 2017
    Kendra D. Conzen, Elizabeth A. Pomfret
    Liver Transplant in Patients with Portal Vein Thrombosis: Medical and Surgical Requirements
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    Date de mise en ligne : Jeudi 17 aot 2017
    Kwan Man
    Recurrent Malignancy – Are we pushing the envelope?
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    Date de mise en ligne : Jeudi 17 aot 2017
    Peter J Friend
    Advances in normothermic perfusion of the liver
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    Date de mise en ligne : Jeudi 17 aot 2017
    Chetan Kalal, Hunaid Hatimi, Ravi Mohanka
    Reconstruction of Anomalous Portal Venous Branching in Right Lobe Living Donor Liver Transplantation and Portal vein thrombosis
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    Date de mise en ligne : Jeudi 17 aot 2017
    Linda Sher, Cristiano Quintini, Sameh Adel Fayek, Peter Abt, Mary Lo, Pui Yan, Lingyun Ji, Susan Groshen, Jamie Case, Christopher Lee Marsh
    Attitudes and barriers to the use of DCD livers: Comparison of a U.S. transplant center survey to the United Network for Organ Sharing data
    Transplantation of liver grafts from donation after circulatory death (DCD) is limited. To identify barriers of DCD livers utilization, all active United States (U.S.) liver transplant centers (n=138) were surveyed and responses compared to the United Network for Organ Sharing (UNOS) data. Seventy‐four centers (54%) responded, and diversity in attitudes was observed, with many not using organ and/or recipient prognostic variables defined in prior studies and UNOS data analysis. Most centers (74%) believed lack of a system allowing a timely re‐transplant is a barrier to utilization. UNOS data demonstrated worse 1 and 5 year patient‐ and graft survival in DCD (86% and 64% and 82% and 59% respectively) versus donation after brain death (DBD) recipients (90% and 71% and 88% and 69% respectively). Donor alanine aminotransferase (ALT), recipient model for end‐stage liver disease (MELD) and cold ischemia time (CIT) significantly impacted DCD outcomes to a greater extent than DBD outcomes. At 3 years, relisting and re‐transplant rates were 7.9% and 4.6% higher in DCD recipients. To optimize outcome our data supports the use of DCD liver grafts with CIT <6‐8 hours in patients with MELD ≤20. In conclusion, standardization of donor and recipient criteria, defining the impact of ischemic cholangiopathy, addressing donor hospital policies, and developing a strategy for timely re‐transplant may help to expand the use of these organs. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Jeudi 17 aot 2017
    Catherine de Magnée, Francis Veyckemans, Thierry Pirotte, Renaud Menten, Dana Dumitriu, Philippe Clapuyt, Karlien Carbonez, Catherine Barrea, Thierry Sluysmans, Christine Sempoux, Isabelle Leclercq, Francis Zech, Xavier Stephenne, Raymond Reding
    Liver and systemic hemodynamics in cirrhotic children: Impact on the surgical management in pediatric living donor liver transplantation
    Background and aims: Cirrhosis in adults is associated with modifications of systemic and liver hemodynamics, whereas little is known about the pediatric population. The aim of this work was to investigate whether alterations of hepatic and systemic hemodynamics were correlated with cirrhosis severity in children. The impact of hemodynamic findings on surgical management in pediatric living donor liver transplantation was evaluated. Methods: Liver and systemic hemodynamics were studied prospectively in 52 children (median age= 1 year; 33 biliary atresia). The hemodynamics of native liver were studied preoperatively by Doppler‐ultrasound, and intraoperatively using invasive flowmetry. Porto‐systemic gradient was invasively measured. Systemic hemodynamics were studied preoperatively by Doppler transthoracic echocardiography, and intraoperatively using transpulmonary thermodilution. Hemodynamic parameters were correlated with pediatric end‐stage liver disease score and the histological degree of fibrosis (collagen proportionate area). Results: Cirrhosis was associated with a 60% reduction of pre‐transplant total liver flow (n=46; median= 36 ml/min/100 g of liver), compared to non‐cirrhotic livers (n=6; median= 86 ml/min/100 g) (p=0.002). Total blood flow into native liver was negatively correlated with PELD (p < 0.001), and liver collagen proportionate area (p=0.005). Median porto‐systemic gradient was 14.5 mmHg in cirrhotic children, and positively correlated with PELD (p < 0.001). Portal vein hypoplasia was observed mainly in children with biliary atresia (p=0.02). Systemic hemodynamics were not altered in our cirrhotic children. Twenty‐one children met the intraoperative criteria for portal vein reconstruction using portoplasty technique during liver transplant procedure, and had a smaller portal vein diameter at pre‐transplant Doppler‐ultrasound (median=3.4mm) (p < 0.001). Conclusions: Cirrhosis in children appears also as a hemodynamic disease of the liver, correlated with cirrhosis severity. Surgical technique for portal vein reconstruction during liver transplantation was adapted accordingly. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Jeudi 17 aot 2017
    A.J. Demetris
    Long Term Outcome of the Liver Graft: The Pathologist Perspective
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    Date de mise en ligne : Jeudi 17 aot 2017
    Christian Jansen, Alexander Cox, Robert Schueler, Matthias Schneider, Jennifer Lehmann, Michael Praktiknjo, Alessandra Pohlmann, Johannes Chang, Steffen Manekeller, Georg Nickenig, Gabriela Berlakovich, Christian P. Strassburg, Christoph Hammerstingl, Katharina Staufer, Jonel Trebicka
    Increased myocardial contractility identifies decompensated cirrhotic patients requiring liver transplantation
    Background: Late allocation of organs for transplant impairs post liver transplant (LT) survival. Cardiac dysfunction, especially diastolic and autonomic dysfunction, is frequent and plays an important role in the prognosis of cirrhotic patients. However, the role of myocardial contractility is unexplored and its prognostic value is controversially discussed. This study analyses the role of myocardial contractility assessed by speckle tracking echocardiography in LT allocation. Methods: 168 cirrhotic patients (training cohort: 111, validation cohort: 57) awaiting LT in two centers were included in this retrospective study. Results: 51 patients from the training and all patients from the validation cohort were transplanted; 36 patients of the training and 38 of the validation cohort were alive at the end of follow‐up; 21 non‐transplanted patients died. Contractility of the left ventricle increased with severity of the Child‐Pugh score. Interestingly, higher left ventricular contractility in the training cohort patients, especially in those with Child‐Pugh C, was an independent predictor of reduced transplant‐free survival. In male patients, the effects on survival of increased left and right ventricular myocardial contractility were more pronounced. Of note, competing risk analysis demonstrated that increased contractility is associated with earlier LT, which could be confirmed in the validation cohort. Importantly, left ventricular myocardial contractility had no impact on survival of patients not receiving LT or on post LT survival. Conclusion: This study demonstrates for the first time that increased myocardial contractility in decompensated patients identifies patients who require LT earlier, but without increased post LT mortality. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Jeudi 17 aot 2017
    Yoshikuni Kawaguchi, Kiyoshi Hasegawa, Naoki Okura, Harufumi Maki, Nobuhisa Akamatsu, Junichi Kaneko, Junichi Arita, Yoshihiro Sakamoto, Kuni Ohtomo, Norihiro Kokudo
    Influence of Outflow‐obstructed Liver Volume and Venous Communication Development: A Three‐dimensional Volume Study in Living Donors
    Background: Living‐donor liver transplantation using the left liver graft with the middle hepatic vein (MHV) is a well‐established procedure. Following such procedures, outflow obstruction occurs in remnant livers. However, the effects of the outflow‐obstructed liver volume (LVOut‐Ob), with or without venous communication development, remain unclear. The aim of the study is to investigate effects of outflow‐obstructed regions by focusing on short‐term outcomes and remnant liver hypertrophy in left liver procurement donors. Methods: Of 532 donors, we collected data from 119 undergoing left liver procurement with the MHV. Postoperative hepatic parameters, venous communication development, and liver hypertrophy were evaluated in two donor groups based on LVOut‐Ob. Results: The left liver was procured with the MHV in 119 donors, who formed two more groups based on the median LVOut‐Ob: large‐outflow‐obstruction (n=60; LVOut‐Ob ≥263 mL) and small‐outflow‐obstruction (n=59; LVOut‐Ob <263 mL). Postoperative liver function parameters were significantly impaired in the large‐outflow‐obstruction group compared with the small‐outflow‐obstruction group. Postoperative venous communication developed in 52 (66.7%) of 78 donors analysed. Hypertrophy ratios in remnant right livers and right paramedian sectors were significantly higher in the small‐outflow‐obstruction group than the large‐outflow‐obstruction group (P = .01 and P = .02, respectively). Liver hypertrophy ratio of outflow‐obstructed regions was better, especially in small regions developing venous communication (P = .001). Postoperative morbidity rate did not differ significantly (P = .66). Conclusions: The procurement of left liver graft with the MHV was safely performed with minimal morbidity by assessing the donor remnant right liver volume with and without outflow obstruction. Attention should be payed that postoperative hepatic parameters and remnant liver hypertrophy were impaired in the remnant livers with large outflow‐obstructed regions compared with those with small outflow‐obstructed regions. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Jeudi 17 aot 2017
    Rohan Vinayak, Ruy J. Cruz, Sarangarajan Ranganathan, Ravi Mohanka, George Mazariegos, Kyle Soltys, Geoff Bond, Sameh Tadros, Abhinav Humar, J Wallis Marsh, Robert R. Selby, Jorge Reyes, Kimberly Haberman, Rakesh Sindhi
    Pediatric liver transplantation for hepatocellular cancer and rare liver malignancies: US multi‐ and single‐center experience (1981‐2015)
    Pediatric liver transplantation (LTx) is increasingly performed for rare unresectable liver malignancies other than hepatoblastoma (HBL). Purpose: We performed a retrospective review of outcomes after LTx for malignancy in the multi‐center US Scientific Registry for Transplant Recipients (SRTR, n=677, 1987‐2015). We then reviewed the Children's Hospital of Pittsburgh (CHP, n=74, 1981‐2014) experience focusing on LTx for unresectable hepatocellular cancer (HCC), non‐HBL embryonal tumors (EMB) and metastatic liver tumors (METS). HBL was included to provide reference statistics. Results: In the SRTR database, LTx for HCC and HBL increased over time (p<0.001). Compared with other malignancies, the 149 HCC cases received fewer segmental grafts (p<0.001) and also experienced 10‐year patient survival similar to 15710 adult HCC LTx recipients (51.6% vs 49.6%, p=0.848, NS, log‐rank test). For 22 of 149 cases with incidental HCC, 10‐year patient survival was higher than 127 primary HCC cases (85%, 95%CI 70.6‐100% vs 48.3%, 95% CI 38‐61%, p=0.168, NS) and similar to 3392 biliary atresia cases (89.9%, 95%CI 88.7‐91%). Actuarial 10‐year patient survival for 17 EMB, 10 METS, six leiomyosarcoma exceeded 60%, approaching survival for HBL. At CHP, post‐transplant recurrence free and overall survival among 25 HCC, 17 (68%) of whom had pre‐existing liver disease, was 16/25 or 64%, and 9/25 or 36%, respectively. All 10 incidental HCC and TNM stage I and II HCC survived recurrence‐free. Only vascular invasion predicted poor survival in multivariate analysis (p<0.0001). Four of five EMB (80%) and all METS (neuroendocrine‐2, pseudopapillary pancreatic‐1) also survived recurrence‐free. Conclusions: Among children, LTx can be curative for unresectable HCC confined to the liver and without vascular invasion, incidental HCC, embryonal tumors and metastatic neuroendocrine tumors. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Jeudi 17 aot 2017
    Sandy Feng, John Bucuvalas
    “Tolerance after liver transplantation: Where are we?”
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    Date de mise en ligne : Mercredi 16 aot 2017
    Sophie Hillaire, Dominique Cazals‐Hatem, Onorina Bruno, Sandra De Miranda, Dominique Grenet, Nicolas Poté, Olivier Soubrane, Serge Erlinger, Florence Lacaille, Francois Mellot, Valerie Vilgrain, Valerie Paradis
    Liver transplantation in adult cystic fibrosis: Clinical, imaging and pathological evidence of obliterative portal venopathy
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    Date de mise en ligne : Mercredi 16 aot 2017
    Pierre‐Alain Clavien, Philipp Dutkowski
    Advances in Hypothermic Perfusion
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    Date de mise en ligne : Mercredi 16 aot 2017
    Rahima A. Bhanji, Kymberly D. Watt
    Fatty Allograft and Cardiovascular Outcomes after Liver Transplantation
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    Date de mise en ligne : Samedi 05 aot 2017
    Henrik H. Junger, Hans J. Schlitt, Edward K. Geissler, Stefan Fichtner‐Feigl, Stefan M. Brunner
    Bile duct regeneration and immune response by passenger lymphocytes signals biliary recovery versus complications after liver transplantation
    Background: This study aimed to elucidate the impact of epithelial regenerative responses and immune cell infiltration on biliary complications after liver transplantation. Methods: Bile duct damage after cold storage was quantified by a BD damage score and correlated with patient outcome in 41 cases. Bacterial infiltration was determined by fluorescence in situ hybridization. Bile duct samples were analyzed by immunohistochemistry for E‐cadherin, cytokeratin, CD56, CD14, CD4, CD8 and double‐immunofluorescence for cytokine production and by mRNA microarray. Results: Increased mRNA levels of adherens‐junctions (p<0.01) were detected in damaged bile ducts from patients without complications compared to damaged bile ducts from patients with biliary complications. Immunohistochemistry showed increased expression of E‐cadherin and cytokeratin in bile ducts without biliary complications (p=0.03; 0.047). Fluorescence in situ hybridization analysis demonstrated translocation of bacteria in bile ducts, however, mRNA analysis suggested an enhanced immune response in bile ducts without biliary complications (p<0.01). Regarding immune cell infiltration, CD4+ and CD8+ cells were significantly increased in patients without complications compared to those with complications (p=0.02; 0.009). Conclusions: Following bile duct damage during cold storage, we hypothesize that the functional regenerative capacity of biliary epithelium and enhanced local adaptive immune cell infiltration are crucial for bile duct recovery. Such molecular immunological bile duct analyses therefore could help to predict biliary complications in cases of “major” epithelial damage after cold storage. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Samedi 05 aot 2017
    Timucin Taner
    Liver Transplantation: Rejection and Tolerance
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    Date de mise en ligne : Samedi 05 aot 2017
    Marc‐Antoine Allard, Felipe Lopes, Fabio Frosio, Nicolas Golse, Antonio Sa Cunha, Daniel Cherqui, Denis Castaing, René Adam, Eric Vibert
    Extreme large‐for‐size syndrome after adult liver transplantation. A model for predicting a potentially lethal complication
    Introduction: There is currently no available tool to predict extreme Large‐for‐size (LFS), a potentially disastrous complication after adult liver transplantation (LT). We aimed to identify the risk factors for extreme LFS and to build a simple predictive model. Methods: A cohort of consecutive patients who underwent LT with full graft in a single institution was studied. The extreme LFS was defined by the impossibility to achieve direct fascial closure, even after delayed management, associated with early allograft dysfunction or non‐function. CT scan‐based measurements of the recipient were done at the level of xiphoid. Results: After 424 LT for 394 patients, extreme LFS occurred in 10 (2.4%) cases. The 90‐day mortality after extreme LFS was 40% vs. 6.5% in other patients (P=0.003). In the extreme LFS group, the male donor‐female recipientcombinationwas more often observed (80.0% vs 17.4%; P<0.001). The graft weight (GW)/right antero‐posterior distance (RAP) ratio was predictive of extreme LFS with the highest area under curve (AUC:0.95). The optimal cut‐off was 100 (sensitivity: 100%; specificity: 88%). The others ratios based on height, weight, body mass index, body surface area, and standard liver volume exhibited lower predictive performance. The final multivariate model included the male donor‐female recipient combination and the GW/RAP. Whenthe GWtoRAP ratio increases from 80, 100,to 120, the probability of extreme LFS was of 2.6%, 9.6% and 29.1% in the male donor‐female recipient combination, and <1%, 1.2%, and 4.5%, in other combinations. Conclusion: The GW/RAP ratiopredicts extreme LFS, and may be helpful to avoid futile refusal for morphological reasons or to anticipate situation at risk, especially in female recipient. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Samedi 05 aot 2017
    Eyal Shemesh, Sarah Duncan, Ravinder Anand, Benjamin L Shneider, Estella M Alonso, George V Mazariegos, Robert S Venick, Rachel A Annunziato, John C Bucuvalas
    Trajectory of adherence behavior in pediatric and adolescent liver transplant recipients ‐ the MALT cohort
    Knowledge of the long term trajectory of nonadherence to immunosupressants can inform decisions regarding organ allocation, adherence monitoring, and intervention efforts. The MALT (Medication Adherence in children who had a Liver Transplant) prospective multi‐site study followed 400 pediatric and adolescent liver transplant recipients for 2 years, using the Medication Level Variability Index (MLVI) to monitor adherence. We hypothesized that adherence is an unstable (fluctuating) phenomenon: that patients who are adherent in year one may become nonadherent in year 2, and vice‐versa. However, we also hypothesized that a majority (more than 50%) of nonadherent patients remain nonadherent over time. We further hypothesized that the longer nonadherence lasts, the higher the likelihood of adverse events (rejection). Finally, we explored the effect of socioeconomic factors on the evolution of adherence over time. Most (59.7%) of MALT patients who were nonadherent in year 1 remained so in year 2; 18.5% of patients who were adherent in year 1 became nonadherent in year 2. Only 4.4% of patients who were adherent in both year 1 and year 2 had a rejection, compared with 22.9% of patients who were nonadherent during one of the years, and 34.9% of those who were nonadherent in both years (p<.001), establishing a “dose dependent” effect of adherence on transplant outcomes. Single‐parent households were associated with worsening adherence. Our results suggest that good baseline adherence does not guarantee adherence later on, that nonadherence is likely to persist in the absence of interventions, and that monitoring of adherence and interventions to improve it should be expected to last for years if transplant outcomes are to be improved. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Samedi 05 aot 2017
    Behnam Saberi, James P. Hamilton, Christine M. Durand, Zhiping Li, Benjamin Philosophe, Andrew M. Cameron, Mark S. Sulkowski, Ahmet Gurakar
    Utilization of Hepatitis C RNA‐positive Donor Liver for Transplant to Hepatitis C RNA‐Negative Recipient
    n/a


    Date de mise en ligne : Samedi 05 aot 2017
    Francia Díaz Jaime, Marina Berenguer
    Pushing the Donor Limits: deceased donor liver transplantation using organs from octogenarian donors
    n/a


    Date de mise en ligne : Samedi 05 aot 2017
    Simone I Strasser
    Long Term Outcome of the Liver Graft: A Clinician Perspective: Recurrent Disease: The Universal Shifting
    n/a


    Date de mise en ligne : Vendredi 28 juillet 2017
    L.W. Unger, G. Berlakovich, M. Trauner, T. Reiberger
    Management of portal hypertension before and after liver transplantation
    Orthotopic liver transplantation (OLT) represents a curative treatment option for end‐stage liver disease (ESLD). While epidemiology of ESLD has recently changed due the rising prevalence of non‐alcoholic fatty liver disease (NAFLD) and decreased burden of hepatitis C virus (HCV) infections due to highly‐effective antiviral regimens, the management of portal hypertension (PHT) remains a clinical challenge in the pre‐ and post‐OLT setting. The measurement of hepatic venous pressure gradient (HVPG) represents the most reliable, but invasive tool for assessment of the severity of PHT. Although novel liver ultrasound and MR‐based elastography methods have been developed, their value to screen for liver fibrosis and PHT in transplanted patients remains to be established. Non‐selective beta‐blockers (NSBBs) represent the cornerstone of medical treatment of PHT, but more studies on their effects on clinical endpoints after OLT are needed. Statins are widely used to treat hyperlipidemia ‐ a common condition after OLT. While a growing body of evidence suggests that statins decrease portal pressure and PHT‐related complications in ESLD, studies on potential benefits of statins after OLT are lacking. Finally, transjugular intrahepatic portosystemic shunts (TIPS) are effective in decreasing PHT and seem to decrease mortality on the OLT waiting list. Moreover, TIPS does not impact on liver function nor complicate the transplant surgical procedures. TIPS may also be used post OLT but the evidence is limited. In conclusion, while the management of PHT in patients with ESLD is based on strong evidence, further data on the value of non‐invasive monitoring tools, as well as on medical and invasive treatment options in the post‐OLT setting are needed to improve management strategies in patients with recurrent PHT after liver transplantation. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Vendredi 28 juillet 2017
    Pramod Kumar, Sunil Taneja, Virendra Singh
    Beta‐blockers in patients with advanced liver disease: Has the dust settled?
    n/a


    Date de mise en ligne : Vendredi 28 juillet 2017
    Mohamed Safwan, Kelly M Collins, Marwan S Abouljoud, Reena Salgia
    Outcome of liver transplantation in patients with prior bariatric surgery
    Non‐alcoholic fatty liver disease is becoming the leading cause of disease resulting in liver transplantation (LT). As a result of this trend, more liver transplant candidates are presenting with prior history of bariatric surgery (BS). Over the last decade, 960 patients underwent LT at our institution; 11 (1.1%) had prior BS. Most common type of BS was Roux‐en‐Y gastric bypass (n=9) with 1 sleeve gastrectomy and 1 jejunoileal bypass. Nine patients underwent LT alone and 2 underwent simultaneous liver‐kidney transplantation. Most common indication for LT was non‐alcoholic steatohepatitis (n=10) with 5 having additional diagnosis of alcoholic liver disease. Thirty‐day reoperation rate was 36.4% (n=4); indications were bile duct repair (n=3) and wound repair (n=1). In first 6 months after LT, biliary complications were seen in 54.5% (n=6) of the patients. Both patient and graft survival rates at 1 and 2 years were 81.8% (n=9) and 72.7% (n=8), respectively. Eight patients (72.7%) had indications for liver biopsy post‐LT; significant macro‐vesicular steatosis was found in 2 (18.2%). In patients with history of alcohol consumption, 2 (40.0%) relapsed post‐LT. Two patients (18.2%) had history of diet‐controlled diabetes pre‐LT; 1 of these patients became insulin dependent post‐LT. Mean body mass index at LT was 31.0±5.7. Mean body mass index at 1, 6, and 12 months post LT was 28.3±5.8, 28.0±3.2 and 31.0±6.6, respectively. Mean preoperative albumin was 2.6±0.6 mg/dl. Patients showed improvement in albumin post‐LT, with mean albumin of 2.7±0.6 and 3.2±0.5 mg/dl, at 1 and 3 months, respectively. Liver profile was stable post‐LT, with mean AST of 32.9±18.4 and 26.6±19.8 IU/L and ALT of 28.0±17.5 and 30.2±17.0 IU/L at 6 and 12 months, respectively. In conclusion, outcomes of LT patients with prior BS are comparable to other transplant recipients with regards to patient and graft survival, and post‐LT complication rates. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Vendredi 28 juillet 2017
    Carlos Moctezuma‐Velazquez, Sylvia Kalainy, Juan G Abraldes
    Reply to: “Non selective beta blockers in cirrhosis and ascites: The need for an accurate method to response guided therapy.”
    n/a


    Date de mise en ligne : Vendredi 28 juillet 2017
    Radika Soysa, Xia Wu, I. Nicholas Crispe
    Dendritic Cells In Hepatitis and Liver Transplantation
    Dendritic cells (DCs) play a key role in innate immune responses, and are also the most effective cells for the activation of T cell immunity. They acquire antigen and process it, then display in on the cell surface bound in a non‐covalent complex with HLA molecules of class I (HLA‐A, B, C) and class II (HLA‐DR). These cells are subdivided into three main subsets, two called myeloid or classical DCs of types 1 and 2, and one called plasmacytoid. The myeloid DCs process and present antigen, while the plasmacytoid DCs also strongly respond to viral signals by secreting Type 1 Interferon. In the liver, all of these subsets are present, but their relative abundance is different from the peripheral blood, and it is further modified by liver disease. It appears that in relation to T cell tolerance, both mDCs and pDCs are influenced by the liver milieu and promote T cell inactivation. However in anti‐viral responses and in ischemia‐reperfusion injury, where innate immune functions are more important, mDCs and pDCs have distinct roles. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Jeudi 27 juillet 2017
    Diego Moya‐Nájera, Ángel Moya‐Herraiz, Luis Compte‐Torrero, David Hervás, Sebastien Borreani, Joaquin Calatayud, Marina Berenguer, Juan C. Colado
    Combined resistance and endurance training at a moderate‐high intensity improves physical condition and quality of life in liver transplant patients
    Background: Although currently, moderate and high intensity concurrent physical exercise is prescribed in populations with special needs due to its greater effect on physical condition and health‐related quality of life (HRQOL), there are no data in the liver transplantation (LT) setting. Aim: To evaluate changes in maximal strength, aerobic capacity, body composition, liver function, and HRQOL in LT patients after a moderate to high intensity combined resistance‐endurance training. Material and methods: 6 months after LT, 54 patients were randomized into two groups: intervention group (IG) and control group (CG). 50 patients completed the study with repeat testing at 6 and 12 months after LT. IG completed a six‐month exercise training program, consisting of two days per week exercises during 24 weeks in the hospital facilities, while CG followed usual care recommendations. Patients completed a five multijoint exercises circuit with elastic bands involving the major muscle groups. The effects of the concurrent training program on maximal oxygen consumption (VO2peak), overall and regional maximal strength, body composition, liver function, and HRQOL were analyzed. Results: The IG showed a significant improvement (p<0.05) in outcome measurements compared to CG in aerobic capacity, hip extension, elbow flexion and overall maximal strength, and physical functioning and vitality of HRQOL, while no changes were observed in body composition and liver function tests. Adherence to the program was 94%. Conclusion: This is the first study that combines supervised resistance and aerobic training performed at moderate to high intensity in LT recipients results in significant improvements in aerobic capacity, maximal strength, and HRQOL. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Lundi 24 juillet 2017
    Bartley Thornburg, Nitin Katariya, Ahsun Riaz, Kush Desai, Ryan Hickey, Robert Lewandowski, Riad Salem
    Interventional radiology in the management of the liver transplant patient
    Liver transplantation is commonly used to treat patients with end‐stage liver disease. The evolution of surgical techniques, endovascular methods, and medical care has led to a progressive decrease in post‐transplant morbidity and mortality. Despite these improvements, a multi‐disciplinary approach to each patient remains essential as the early diagnosis and treatment of the complications of transplantation influence graft and patient survival. The critical role of interventional radiology in the collaborative approach to the care of the liver transplant patient will be reviewed. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Samedi 22 juillet 2017
    Ahmer M. Hameed, Jerome M. Laurence, Vincent W.T. Lam, Henry C. Pleass, Wayne J. Hawthorne
    A systematic review and meta‐analysis of cold in situ perfusion and preservation of the hepatic allograft: working towards a unified approach
    Background: The efficacy of cold in situ perfusion and static storage of the liver is one possible determinant of transplantation outcomes. The aim of this study was to determine whether there is evidence to substantiate a preference for a particular perfusion route (aortic or dual) or perfusion/preservation solution in donation after brain‐death (DBD) liver transplantation. Methods: The Embase, Medline and Cochrane databases were utilized (1980‐2017). Random effects modeling was used to estimate effects on transplantation outcomes based upon (i) aortic or dual in situ perfusion, and (ii) the use of University of Wisconsin (UW), histidine‐tryptophan‐ketoglutarate (HTK), Celsior and/or Institut Georges Lopez‐1 (IGL‐1) for perfusion/preservation. Results: Twenty‐two articles were included (2294 liver transplants). The quality of evidence ranged from very low to moderate (GRADE score). Meta‐analyses were conducted for 14 eligible studies. Whilst there was no difference in the primary non‐function (PNF) rate, a higher peak alanine aminotransferase (ALT) was recorded in dual compared to aortic‐only UW‐perfused livers (Standardized Mean Difference 0.24; 95% CI 0.01‐0.47); a back‐table portal venous flush was undertaken in the majority of aortic‐only perfused livers. There were no relevant differences in peak enzymes, PNF, thrombotic graft loss, biliary complications or one‐year graft survival in comparisons between dual‐perfused livers using UW, HTK, Celsior or IGL‐1. Conclusion: There is no significant evidence that aortic‐only perfusion of the DBD liver compromises transplantation outcomes, and may be favored owing to its simplicity. However, there is currently insufficient evidence to advocate for the use of any particular perfusion/preservation fluid over the others. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Samedi 22 juillet 2017
    Jennifer Lai
    Transplant for the very sick: No limitations in donor quality?
    n/a


    Date de mise en ligne : Samedi 22 juillet 2017
    Matyas Hamar, Markus Selzner
    Steatotic Donor Livers: Where is the Risk‐Benefit Maximized?
    n/a


    Date de mise en ligne : Samedi 22 juillet 2017
    Seong Hoon Kim, Eung Chang Lee, Jae Ryong Shim, Sang Jae Park
    Right Lobe Living Donors Ages 55 and Older in Liver Transplantation
    Insufficient is the evidence for safe use of elderly donors in adult‐to‐adult living donor liver transplantation (LDLT). The aim of this study was to evaluate the outcomes of right lobe LDLT by donor age (≥55 vs. <55 years). All living donors who underwent right hepatectomy at the authors' institution between March 2008 and December 2015 were divided into 2 groups: group A with an age ≥ 55 and group B with an age < 55. The selection criteria for elderly donor were preservation of middle hepatic vein, remnant liver volume ≥30%, and no or mild fatty liver. The matching criteria of recipients for the elderly donor grafts were model for end‐stage liver disease score<25, graft‐to‐recipient weight ratio>0.8%, and body mass index<25kg/m2. Perioperative data, complications by the Clavien classification, and the outcomes with at least 12 months follow‐up were compared. Forty‐two donors were enrolled in group A and 498 in group B. No significant differences in operative parameters were observed between the two groups. The peak postoperative AST, ALT, and total bilirubin levels made no difference between the two groups. The peak INR level was significantly lower in group A than in group B (p=0.001). All donors recovered completely with no significant differences in overall complications between the two groups. All recipients of grafts from donors in group A showed good initial function with no significant differences in 1‐year graft and patient survival or biliary complications between two groups. These results provide clinical evidence for feasibility of right hepatectomy in living donors aged ≥ 55 years without compromising donor safety or recipient outcomes. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Mardi 18 juillet 2017
    Kojiro Nakamura, Shoichi Kageyama, Bibo Ke, Takehiro Fujii, Rebecca A. Sosa, Elaine F. Reed, Nakul Datta, Ali Zarrinpar, Ronald W. Busuttil, Jerzy W. Kupiec‐Weglinski
    Sirtuin 1 Attenuates Inflammation and Hepatocellular Damage in Liver Transplant Ischemia‐Reperfusion: From Mouse‐to‐Human
    Hepatic ischemia‐reperfusion injury (IRI), an inevitable antigen‐independent inflammation response in cadaveric liver transplantation, correlates with poor early graft function, rejection episodes, and contributes to donor organ shortage. Sirtuin 1 (SIRT1) is a histone deacetylase which may regulate inflammatory cell activity and manage liver function in IRI, though its functional role and clinical relevance remains to be elucidated. We investigated the efficacy of SIRT1 activation in murine liver IRI model and verified the concept of putative SIRT1‐mediated hepatoprotection in clinical liver transplantation. In the experimental arm, mice were subjected to 90min of liver partial warm ischemia followed by 6h of reperfusion with or without adjunctive SIRT1 activation in vivo (Resveratrol, Res). In parallel, bone marrow‐derived macrophage (BMDM) or spleen lymphocyte cultures were treated with Res. In the clinical arm, liver biopsies from twenty‐one adult primary liver transplant patients (2h post‐reperfusion) were divided into “low” (n=11) vs. “high” (n=10) SIRT1 expression groups, assessed by Western blots. Treatment with Res attenuated murine liver IRI while upregulating SIRT1, suppressing leukocyte infiltration and decreasing pro‐inflammatory cytokine programs. SIRT1 silencing (siRNA) in BMDM cultures enhanced inflammatory cytokine program whereas addition of Res decreased proinflammatory response in SIRT1‐dependent manner. In addition, Res decreased IFNγ production in liver‐infiltrating and spleen lymphocyte cultures. Human liver transplants with high‐SIRT1 levels showed improved hepatocellular function and superior survival (p=0.04), accompanied by lower pro‐inflammatory cytokine profile. In conclusion, our translational study is the first to identify SIRT1 as a regulator of hepatocellular function in human liver transplant recipients under IR‐stress. By targeting innate and adaptive immune activation, manipulation of SIRT1 signaling should be considered as novel means to combat inflammation in liver transplantation. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Mardi 18 juillet 2017
    Sandy Feng
    Living Donor Liver Transplantation (LDLT) in High MELD Score Patients
    n/a


    Date de mise en ligne : Mardi 18 juillet 2017
    George V. Mazariegos
    Critical elements in pediatric allograft selection
    n/a


    Date de mise en ligne : Mardi 18 juillet 2017
    Masayuki Hisada, Xiuying Zhang, Yoshihiro Ota, Andrew M Cameron, James Burdick, Bin Gao, George Melville Williams, Zhaoli Sun
    Fibrosis in Small Syngeneic Rat Liver Grafts Due to Damaged Bone Marrow Stem Cells from Chronic Alcohol Consumption
    A patient with liver failure due to chronic and acute alcohol abuse under consideration for an urgent liver transplant shortly after stopping alcohol may have residual abnormalities that threaten transplant success, particularly for a small graft. To address this, we studied a model in which reduced size (50%) Lewis rat livers are transplanted into green fluorescence protein (GFP) transgenic Lewis recipients after they are fed alcohol or a control diet for 5 weeks. Here we show that normal small Lewis grafts transplanted to alcohol fed Lewis hosts developed fibrosis whereas no fibrosis was observed in control fed recipients. Host derived CD133+ cells were significantly increased in livers recovered from both alcohol fed and control recipients, but only alcohol fed recipients demonstrated 8‐OHdG co‐staining (a marker of oxidative DNA damage). α‐SMA staining, a marker for myofibroblasts, also co‐localized with CD133+ cells only in the livers of alcohol fed recipients. Immunostaining and PCR analysis confirmed that chronic alcohol consumption decreased the proportion of bone marrow stem cells expressing CD133, c‐Kit and CXCR4 markers and caused oxidative mitochondria (mt) DNA damage. Culture of CD133+ cells from normal rats with medium containing 3% ethanol for 48 hours resulted in elevated mitochondrial 8‐OHdG and mtDNA deletion, and ethanol exposure diminished CD133 expression but dramatically increased α‐SMA expression. In conclusion, oxidative mtDNA damage and deletions occur in bone marrow stem cells of chronic alcohol fed recipients and these damaged cells mobilize to the small liver grafts and become myofibroblasts where they play a key role in the subsequent development of fibrosis. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Jeudi 13 juillet 2017
    Jennifer K.L Chow, Tomas Ganz, Robin Ruthazer, Mary Ann Simpson, Elizabeth A. Pomfret, Fredric D. Gordon, Mark E. Westerman, David R. Snydman
    Iron‐Related Markers are Associated with Infection after Liver Transplantation
    Though serum iron has been known to be associated with an increased risk of infection, hepcidin, the major regulator of iron metabolism, has never been systematically explored in this setting. Finding early biomarkers of infection, such as hepcidin, could help identify patients in whom early empiric antimicrobial therapy would be beneficial. We prospectively enrolled consecutive patients (N=128) undergoing first time, single organ orthotopic liver transplantation (OLT) without known iron overload disorders at two academic hospitals in Boston from August 2009‐November 2012. Cox regression compared the associations between different iron markers and the development of first infection at least one week after OLT. 47 (37%) patients developed a primary outcome of infection at least one week after OLT and one patient died. After adjusting for peri‐operative bleeding complications, number of hospital days, and hepatic artery thrombosis, changes in iron markers were associated with the development of infection post‐OLT including: increasing ferritin (hazards ratio [HR], 1.51 [95% CI, 1.12 ‐ 2.05]), rising ferritin slope (HR, 1.10 [95% CI, 1.03 ‐1.17]), and increasing hepcidin (HR, 1.43 [95% CI, 1.05‐1.93]). A decreasing iron (HR, 1.76 [95% CI, 1.20‐2.57]) and a decreasing iron slope (HR, 4.21 [95% CI, 2.51‐7.06]) were also associated with subsequent infections. Conclusion: Hepcidin and other serum iron markers and their slope patterns or their combination are associated with infection in vulnerable patient populations. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Lundi 10 juillet 2017
    Shih‐Ho Wang, Poh‐Yen Loh, Ting‐Lung Lin, Li‐Man Lin, Wei‐Feng Lee, Yu‐Hung Lin, Chih‐Che Lin, Chao‐Long Chen
    Active Immunization for Prevention of De Novo HBV infection after Adult Living Donor Liver Transplantation with HBc(+) Graft
    Background De novo hepatitis B infection (DNHB) may occur in recipients who do not receive prophylaxis after liver transplantation (LT) with anti‐HBc(+) donor grafts. Active immunization has been shown to prevent DNHB in pediatric recipients. Our aim is to investigate the efficacy of HBV vaccination for preventing DNHB in adult living donor LT (LDLT). Patients and Methods 71 adult HBsAg(‐) LDLT patients who received anti‐HBc(+) grafts from 2000 to 2010 were enrolled into this study. Patients were given HBV vaccinations with the aim of achieving anti‐HBs >1000 IU/L pre‐transplant and >100 IU/L post‐transplant. The cohort was stratified into 3 groups: patients with pre‐transplant anti‐HBs titer >1000 IU/L without need for post‐transplant prophylaxis (group 1, n=24), patients with pre‐transplant low titer <1000 IU/L who were given post‐transplant lamivudine prophylaxis and responded appropriately to post‐transplant vaccination by maintaining anti‐HBs titers >100 IU/L (group 2, n=30), and low titer nonresponders (anti‐HBs titer <100 IU/L despite vaccination), for whom lamivudine was continued indefinitely (group 3, n=17). Results All DNHB occurred in group 3 patients with posttransplant anti‐HBs levels <100 IU/L, with an incidence rate of 17.6% compared to 0% in patients with posttransplant anti‐HBs >100 IU/L (p=0.001). Pre‐transplant anti‐HBs level of >1000 IU/L was significantly associated with early attainment and sustained level of posttransplant anti‐HBs of >100 IU/L (p <0.001). Conclusion Active immunization is effective in preventing DNHB in adult LDLT if the post‐transplant anti‐HBs level is maintained above 100 IU/L with vaccination. Anti‐viral prophylaxis can be safely discontinued in patients who obtain this immunity. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Samedi 08 juillet 2017
    J.C. Olson, C.J. Karvellas
    Critical Care management of the cirrhotic patient awaiting liver transplant in the Intensive Care Unit
    Patients with cirrhosis who are awaiting liver transplantation are at high risk for development of critical illness. Current liver allocation policies which dictate a "sickest first" approach coupled with a mismatch between need and availability of organs results in longer wait times and thus, patients are becoming increasingly ill while awaiting organ transplantation. Even patients with well compensated cirrhosis may suffer acute deterioration, the syndrome of acute‐on‐chronic liver failure (ACLF) results in multi‐system organ dysfunction and a marked increase in associated short‐term morbidity and mortality. For patients on transplant waiting lists, the development of multi‐system organ failure may eliminate candidacy for transplant by virtue of being "too sick" to safely undergo transplantation surgery. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (e.g. infection and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo liver transplantation. Management of the critically ill ACLF patient awaiting transplantation is best accomplished by multidisciplinary teams with expertise in critical care and transplant medicine. Such teams are well suited to address the needs of this unique patient population and to identify patients who may be too ill to proceed to transplantation surgery. The focus of this review is to identify the common complications of ACLF and our approach management in critically ill patients awaiting liver transplantation in our centers. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Samedi 08 juillet 2017
    Elsa Solà, Pere Ginès
    Pro: Acute‐on‐chronic liver failure
    n/a


    Date de mise en ligne : Lundi 26 juin 2017
    John C. LaMattina, Samuel Sultan, Steven I. Hanish, David A. Bruno, Paul J. Thuluvath, Anurag Maheshwari, Rolf N. Barth
    Previous Live Donor Hemi‐Hepatectomy as Cadaveric Donor of Remnant Liver
    n/a


    Date de mise en ligne : Lundi 26 juin 2017
    Mohammed Al Sebayel, Faisal Abaalkhail, Saleh Al Abbad, Hamad AlBahili, Hussien Elsiesy, Maha Aleid, Waleed Al‐hamoudi
    Liver Transplantation in the Kingdom of Saudi Arabia
    The first liver transplant in Saudi Arabia was performed in 1991; however, it was not until 1994 that the first structured liver transplant program was launched. Until 1997, all liver transplants in the Kingdom of Saudi Arabia (KSA) were deceased donor liver transplantations. Programs performing liver transplants needed the authorization of the Saudi Center for Organ Transplantation (SCOT), which provides the essential support for organ procurement and allocation as well as regulatory support for organ transplantation in the country. Currently, there are four (4) liver transplant centers in KSA. Three (3) centers are in Riyadh, the capital city of KSA, and one is in the city of Dammam in the Eastern province. Pediatric living donor liver transplantation began in 1997, while the adult living donor liver transplantation program started four years later, in 2001. Currently, more than 2000 liver transplants have been performed by the 4 centers in KSA. Over 50% of those were performed at King Faisal Specialist Hospital & Research Center (KFSH&RC) in Riyadh. The outcomes of these transplants have been comparable to the international standards. The aim of this review is to provide an overview of liver transplantation in KSA. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Lundi 26 juin 2017
    Andreas Umgelter, Alexander Hapfelmeier, Wouter Kopp, Marieke van Rosmalen, Xavier Rogiers, Markus Guba,
    Disparities in Eurotransplant liver transplantation waitlist outcome between patients with and without exceptional MELD
    Background: The sickest‐first principle in donor‐liver allocation can be implemented by allocating organs to cirrhotic patients with the highest Model of End‐stage Liver Disease (MELD) scores. For patients with other risk factors, standard (SE) and non‐standard exceptions (NSE) have been developed. We investigated whether this system of matched MELD scores achieves similar outcome on the liver transplant waiting‐list for various diagnostic groups in Eurotransplant (ET) countries with MELD‐based individual allocation (Belgium, The Netherlands and Germany). Methods: A retrospective analysis of the ET waiting‐list outflow from December 2006 until December 2015 was conducted, to investigate the relation of the unified MELD‐based allocation to the risk of a negative waiting‐list outcome (death on the waiting‐list or de‐listing as too sick) as opposed to a positive waiting‐list outcome (transplantation or de‐listing as recovered). Results: 16926 patients left the waiting‐list with a positive (11580) or negative (5346) outcome. 3548 patients had an SE, 330 a NSE. Negative outcome was more common among patients without (N)SE (34.3%) than among patients with SE (22.6%) or NSE (18.6%) (p < 0.001). Analysis by model based recursive partitioning detected five risk groups with different relations of matched MELD to a negative outcome: In Germany: 1) no (N)SE, SE for biliary sepsis; 2) SE for HCC, hepato‐pulmonary syndrome (HPS) or porto‐pulmonary hypertension (PPH); and 3) SE for primary sclerosing cholangitis (PSC) or polycystic liver disease (PcLD). In Belgium and The Netherlands: 4) (N)SE or SE for HPS or PPH; and 5) SE for biliary sepsis, HCC, PcLD or PSC. Conclusion: (N)SE do not even out risks across different diagnostic groups. Patients with SE or NSE appear advantaged towards cirrhotic patients without (N)SE. This article is protected by copyright. All rights reserved.


    Date de mise en ligne : Mercredi 01 avril 2015
    Erratum
    Erratum
    n/a


    Date de mise en ligne : Lundi 21 aot 2017
    Issue Information
    Issue Information
    1098


    Date de mise en ligne : Lundi 21 aot 2017
    Jorge A. Marrero, Amit G. Singal
    Direct‐acting antivirals and recurrence of hepatocellular carcinoma
    1100


    Date de mise en ligne : Lundi 21 aot 2017
    Mehul H. Doshi, Jason Salsamendi, Govindarajan Narayanan
    Portal venous stenosis following liver transplant: Role of transsplenic intervention
    1102


    Date de mise en ligne : Lundi 21 aot 2017
    Alberto Zanetto, Sarah Shalaby, Alessandro Vitale, Claudia Mescoli, Alberto Ferrarese, Martina Gambato, Enrica Franceschet, Giacomo Germani, Marco Senzolo, Antonietta Romano, Paolo Angeli, Massimo Rugge, Fabio Farinati, Daniel M. Forton, Umberto Cillo, Patrizia Burra, Francesco Paolo Russo
    Dropout rate from the liver transplant waiting list because of hepatocellular carcinoma progression in hepatitis C virus–infected patients treated with direct‐acting antivirals
    Concerns about an increased hepatocellular carcinoma (HCC) recurrence rate following direct‐acting antiviral (DAA) therapy in patients with cirrhosis with a prior complete oncological response have been raised. Data regarding the impact of HCV treatment with DAAs on wait‐list dropout rates in patients with active HCC and HCV‐related cirrhosis awaiting liver transplantation (LT) are lacking. HCV‐HCC patients listed for LT between January 2015 and May 2016 at Padua Liver Transplant Center were considered eligible for the study. After enrollment, patients were divided into 2 groups, depending on whether they underwent DAA treatment while awaiting LT or not. For each patient clinical, serological, and virological data were collected. HCC characteristics were radiologically evaluated at baseline and during follow‐up (FU). For transplanted patients, pathological assessment of the explants was performed and recurrence rates were calculated. A total of 23 patients treated with DAAs and 23 controls were enrolled. HCC characteristics at time of LT listing were comparable between the 2 groups. Median FU was 10 and 7 months, respectively, during which 2/23 (8.7%) and 1/23 (4.3%) dropout events due to HCC progression were registered (P = 0.90). No significant differences in terms of radiological progression were highlighted (P = 0.16). A total of 9 out of 23 (39%) patients and 14 out of 23 (61%) controls underwent LT, and histopathological analysis showed no differences in terms of median number and total tumor volume of HCC nodules, tumor differentiation, or microvascular invasion. During post‐LT FU, 1/8 (12.5%) DAA‐treated patient and 1/12 (8.3%) control patient experienced HCC recurrence (P = 0.60). In conclusion, viral eradication does not seem to be associated with an increased risk of dropout due to neoplastic progression in HCV‐HCC patients awaiting LT. Liver Transplantation 23 1103–1112 2017 AASLD.


    Date de mise en ligne : Lundi 21 aot 2017
    Ka Wing Ma, Kenneth S. H. Chok, Albert C. Y. Chan, Henry S. C. Tam, Wing Chiu Dai, Tan To Cheung, James Y. Y. Fung, Chung Mau Lo
    A new formula for estimation of standard liver volume using computed tomography–measured body thickness
    The objective of this article is to derive a more accurate and easy‐to‐use formula for finding estimated standard liver volume (ESLV) using novel computed tomography (CT) measurement parameters. New formulas for ESLV have been emerging that aim to improve the accuracy of estimation. However, many of these formulas contain body surface area measurements and logarithms in the equations that lead to a more complicated calculation. In addition, substantial errors in ESLV using these old formulas have been shown. An improved version of the formula for ESLV is needed. This is a retrospective cohort of consecutive living donor liver transplantations from 2005 to 2016. Donors were randomly assigned to either the formula derivation or validation groups. Total liver volume (TLV) measured by CT was used as the reference for a linear regression analysis against various patient factors. The derived formula was compared with the existing formulas. There were 722 patients (197 from the derivation group, 164 from the validation group, and 361 from the recipient group) involved in the study. The donor's body weight (odds ratio [OR], 10.42; 95% confidence interval [CI], 7.25‐13.60; P < 0.01) and body thickness (OR, 2.00; 95% CI, 0.36‐3.65; P = 0.02) were found to be independent factors for the TLV calculation. A formula for TLV (cm3) was derived: 2 × thickness (mm) + 10 × weight (kg) + 190 with R2 0.48, which was the highest when compared with the 4 other most often cited formulas. This formula remained superior to other published formulas in the validation set analysis (R2, 5.37; interclass correlation coefficient, 0.74). Graft weight/ESLV values calculated by the new formula were shown to have the highest correlation with delayed graft function (C‐statistic, 0.79; 95% CI, 0.69‐0.90; P < 0.01). The new formula (2 × thickness + 10 × weight + 190) represents the first study proposing the use of CT‐measured body thickness which is novel, easy to use, and the most accurate for ESLV. Liver Transplantation 23 1113–1122 2017 AASLD.


    Date de mise en ligne : Lundi 21 aot 2017
    Colin M. Court, Michael P. Harlander‐Locke, Daniela Markovic, Samuel W. French, Bita V. Naini, David S. Lu, Steven S. Raman, Fady M. Kaldas, Ali Zarrinpar, Douglas G. Farmer, Richard S. Finn, Saeed Sadeghi, James S. Tomlinson, Ronald W. Busuttil, Vatche G. Agopian
    Determination of hepatocellular carcinoma grade by needle biopsy is unreliable for liver transplant candidate selection
    The objective of this article is to evaluate the utility of preoperative needle biopsy (PNB) grading of hepatocellular carcinoma (HCC) as a biomarker for liver transplantation (LT) candidate selection. Given the prognostic significance of HCC tumor grade, PNB grading has been proposed as a biomarker for LT candidate selection. Clinicopathologic characteristics of HCC LT recipients (1989‐2014) with a PNB were analyzed, and the concordance of PNB grade to explant grade and vascular invasion was assessed to determine whether incorporation of PNB grade to accepted transplant criteria improved candidate selection. Of 965 patients undergoing LT for HCC, 234 (24%) underwent PNB at a median of 280 days prior to transplant. Grade by PNB had poor concordance to final explant pathology (κ = 0.22; P = 0.003), and low sensitivity (29%) and positive predictive value (35%) in identifying poorly differentiated tumors. Vascular invasion was predicted by explant pathologic grade (rs = 0.24; P < 0.001) but not PNB grade (rs= −0.05; P = 0.50). Increasing explant pathology grade (P = 0.02), but not PNB grade (P = 0.65), discriminated post‐LT HCC recurrence risk. The incorporation of PNB grade to the established radiologic Milan criteria (MC) did not result in improved prognostication of post‐LT recurrence (net reclassification index [NRI] = 0%), whereas grade by explant pathology resulted in significantly improved reclassification of risk (NRI = 19%). Preoperative determination of HCC grade by PNB has low concordance with explant pathologic grade and low sensitivity and positive predictive value in identifying poorly differentiated tumors. PNB grade did not accurately discriminate post‐LT HCC recurrence and had no utility in improving prognostication compared with the MC alone. Incorporation of PNB to guide transplant candidate selection appears unjustified. Liver Transplantation 23 1123–1132 2017 AASLD.


    Date de mise en ligne : Lundi 21 aot 2017
    Joon‐Young Ohm, Gi‐Young Ko, Kyu‐Bo Sung, Dong‐Il Gwon, Heung Kyu Ko
    Safety and efficacy of transhepatic and transsplenic access for endovascular management of portal vein complications after liver transplantation
    The purpose of this article is to evaluate and compare the safety and efficacy of endovascular management of the portal vein (PV) via percutaneous transsplenic access versus percutaneous transhepatic access in liver transplantation (LT) recipients. A total of 18 patients who underwent endovascular management of PV via percutaneous transhepatic (n = 8) and transsplenic (n = 10) access were enrolled. Transsplenic access was chosen if the spleen was located in a normal position, the splenic vein (SpV) was preserved, and the target lesion did not involve confluence of the superior mesenteric and SpVs. Accessibility of the percutaneous transsplenic puncture was confirmed via ultrasound (US) in the angiography suite. All procedures were performed under local anesthesia. Percutaneous transhepatic or transsplenic access was performed using a 21‐gauge Chiba needle under US and fluoroscopic guidance, followed by balloon angioplasty, stent placement, or variceal embolization. The access tract was embolized using coils and a mixture (1:2) of glue and ethiodized oil. Transhepatic or transsplenic access was successfully achieved in all patients. A total of 12 patients underwent stent placement; 3 had balloon angioplasty only; 2 had variceal embolization only; and 1 had variceal embolization followed by successful stent placement. Regarding major complications, 1 patient experienced a SpV tear with extravasation during transsplenic balloon angioplasty, which was successfully managed using temporary balloon inflation, followed by transfusion. Clinical success was achieved in 9 of 11 (82%) patients who exhibited clinical manifestations. The remaining 7 patients who underwent prophylactic endovascular management were healthy. In conclusion, endovascular management of PV via percutaneous transsplenic access is a relatively safe and effective alternative that does not damage the liver grafts of LT recipients. Liver Transplantation 23 1133–1142 2017 AASLD.


    Date de mise en ligne : Lundi 21 aot 2017
    Pratima Sharma, Nathan P. Goodrich, Douglas E. Schaubel, Abigail R. Smith, Robert M. Merion
    National assessment of early hospitalization after liver transplantation: Risk factors and association with patient survival
    Hospitalization is known to occur frequently in the first 6 months following liver transplantation (LT). Using a novel data linkage between the Scientific Registry of Transplant Recipients and Centers for Medicare and Medicaid Services, our study has 2 objectives: (1) to determine risk factors for “early” hospitalization (ie, within 6 months of LT); and (2) to quantify the importance of hospitalization history in the first 6 months with respect to subsequent patient survival (ie, survival, conditional on surviving 6 months post‐LT). The study population consisted of patients aged ≥18 years who underwent deceased donor LT between January 1, 2003 and December 31, 2010, with Medicare as primary or secondary insurance and were discharged alive from the index LT hospitalization (n = 7220). The early hospitalization rate was 2.76 per patient‐year and was significantly associated with many recipient factors (eg, recipient age, hepatitis C, diabetes, poor renal function including dialysis, and recipient of transjugular intrahepatic portosystemic shunt procedure before LT), as well as donor race and donation after cardiac death. Conditional on surviving 6 months after LT, the covariate‐adjusted death rate increased by 22% for each additional hospitalization occurring in the first 6 months (hazard ratio, 1.22; P < 0.001). In conclusion, several LT recipient factors are significantly associated with early hospitalization. Moreover, a patient's hospitalization profile during follow‐up months 0‐6 is a very strong predictor of survival thereafter. Efforts and resources should be devoted toward identifying LT recipients at risk for early hospitalization and modifying the actionable risk factors such as hepatitis C, diabetes, and body mass index to improve resource utilization and overall outcomes. Liver Transplantation 23 1143–1152 2017 AASLD.


    Date de mise en ligne : Lundi 21 aot 2017
    Vinay Sundaram, Jane Lim, Danielle M. Tholey, Sentia Iriana, Irene Kim, Vignan Manne, Nicholas N. Nissen, Andrew S. Klein, Tram T. Tran, Walid S. Ayoub, Barry Schlansky
    The Braden Scale, A standard tool for assessing pressure ulcer risk, predicts early outcomes after liver transplantation
    The Braden Scale is a standardized tool to assess pressure ulcer risk that is reported for all hospitalized patients in the United States per requirements of the Center for Medicare and Medicaid Services. Previous data have shown the Braden Scale can predict both frailty and mortality risk in patients with decompensated cirrhosis. Our aim was to evaluate the association of the Braden Scale score with short‐term outcomes after liver transplantation (LT). We performed a retrospective cohort study of deceased donor LT recipients at 2 centers and categorized them according to the Braden Scale at hospital admission as low (>18), moderate (16‐18), or high risk (<16) for pressure ulcer. We created logistic and Poisson multiple regression models to evaluate the association of Braden Scale category with in‐hospital and 90‐day mortality, length of stay (LOS), nonambulatory status at discharge, and discharge to a rehabilitation facility. Of 341 patients studied, 213 (62.5%) were low risk, 59 (17.3%) were moderate risk, and 69 (20.2%) were high risk. Moderate‐ and high‐risk patients had a greater likelihood for prolonged LOS, nonambulatory status, and discharge to a rehabilitation facility, as compared with low‐risk patients. High‐risk patients additionally had increased risk for in‐hospital and 90‐day mortality after LT. Multiple regression modeling demonstrated that high‐risk Braden Scale score was associated with prolonged LOS (IRR, 1.56; 95% confidence interval [CI], 1.47‐1.65), nonambulatory status at discharge (odds ratio [OR], 4.15; 95% CI, 1.77‐9.71), and discharge to a rehabilitation facility (OR, 5.51; 95% CI, 2.57‐11.80). In conclusion, the Braden Scale, which is currently assessed in all hospitalized patients in the United States, independently predicted early disability‐related outcomes and greater LOS after LT. Liver Transplantation 23 1153–1160 2017 AASLD.


    Date de mise en ligne : Lundi 21 aot 2017
    Xiao‐Shun He, Shun‐Jun Fu, Qiang Zhao, Xiao‐Feng Zhu, Dong‐Ping Wang, Ming Han, Wei‐Qiang Ju, Yi Ma, Xing‐Yuan Jiao, Xiao‐Peng Yuan, An‐Bin Hu, Zhi‐Yong Guo
    A simplified multivisceral transplantation procedure for patients with combined end‐stage liver disease and type 2 diabetes mellitus
    In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end‐stage liver disease and concurrent type 2 DM. Forty‐four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1‐, 3‐, and 5‐year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end‐stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161–1170 2017 AASLD.


    Date de mise en ligne : Lundi 21 aot 2017
    Shinya Okumura, Tadahiro Uemura, Xiangdong Zhao, Yuki Masano, Tatsuaki Tsuruyama, Yasuhiro Fujimoto, Taku Iida, Shintaro Yagi, Dmitri Bezinover, Bruce Spiess, Toshimi Kaido, Shinji Uemoto
    Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats
    The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30‐minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50‐minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171–1185 2017 AASLD.


    Date de mise en ligne : Lundi 21 aot 2017
    Xiao Zhi, Fei Xue, Wei Chen, Chao Liang, Hao Liu, Tao Ma, Xuefeng Xia, Liqiang Hu, Xueli Bai, Tingbo Liang
    OSI‐027 modulates acute graft‐versus‐host disease after liver transplantation in a rat model
    Despite its rarity (1%‐2%), acute graft‐versus‐host disease after liver transplantation (LT‐aGVHD) has a high mortality rate (85%). A gradual decrease in regulatory T cells (Tregs) correlates with disease progression in a rat LT‐GVHD model, and treatments which increase Tregs exert therapeutic effects on LT‐aGVHD. In this study, LT‐aGVHD model rats were treated with rapamycin (RAPA), OSI‐027, or an equal quantity of vehicle. Rats treated with OSI‐027 survived longer (>100 days) than those in the RAPA (70 ± 8 days) or control (24 ± 3 days) groups. Flow cytometric analysis showed that the Treg ratios in peripheral blood mononuclear cells in the OSI‐027 group were higher than those in the RAPA or control groups. The proportions of donor‐derived lymphocytes in the OSI‐027 group were lower than those in the RAPA or control groups. Hematoxylin‐eosin staining of skin tissue demonstrated less severe lymphocyte infiltration in the OSI‐027 group than that in the RAPA or control groups. In vitro, OSI‐027 induced differentiation of CD4+CD25– T cells into CD4+CD25+ forkhead box P3+ Tregs. Furthermore, injection of OSI‐027‐induced donor‐derived CD4+CD25+ T cells into the peripheral blood of LT‐aGVHD model rats prevented LT‐aGVHD. Thus, OSI‐027 is implicated as a novel method for the treatment of LT‐aGVHD. Liver Transplantation 23 1186–1198 2017 AASLD.


    Date de mise en ligne : Lundi 21 aot 2017
    Toshihiro Kitajima, Seisuke Sakamoto, Kengo Sasaki, Hajime Uchida, Soichi Narumoto, Akinari Fukuda, Satoshi Teramukai, Shinji Uemoto, Mureo Kasahara
    Living donor liver transplantation for post‐Kasai biliary atresia: Analysis of pretransplant predictors of outcomes in infants
    After decades of dramatic surgical innovations in pediatric living donor liver transplantation (LDLT), LDLT for biliary atresia (BA) still poses various challenges. This study reviewed our experience with LDLT for children with post‐Kasai BA and evaluated outcomes and prognostic factors. From 2005 to 2016, 168 post‐Kasai BA LDLT patients were enrolled and divided into 3 groups by age. Patient characteristics and perioperative data were compared. Predictors of morbidity and mortality following LDLT were analyzed in 93 infants. Outcome was relatively worse in infants than older children, with overall survival at 1 and 5 years of 94.5% and 93.2%, respectively, and graft survival at 1 and 5 years of 91.1% each. Incidence of vascular complications was not significantly higher in infants. High Pediatric End‐Stage Liver Disease (PELD) score (odds ratio [OR], 3.72; 95% confidence interval [CI], 1.30‐10.67; P = 0.02) and portal vein (PV) hypoplasia (OR, 3.23; 95% CI, 1.10‐9.52; P = 0.03) were independent risk factors for morbidity. Low weight‐for‐age z score (hazard ratio, 5.76; 95% CI, 1.05‐31.47; P = 0.03) was identified as a significant risk factor for mortality after LDLT, but not age or absolute body weight (BW). Infants with BW deficit had a significantly smaller PV diameter (P = 0.005), greater blood loss (P = 0.001), and higher incidence of postoperative bacteremia (P = 0.01). In conclusion, high PELD score and PV hypoplasia were independent risk factors for morbidity, and BW deficit was associated with poor survival in infants with post‐Kasai BA after LDLT. However, LDLT in these infants at the earliest possible time after referral is a feasible option with excellent patient survival in an experienced center. Liver Transplantation 23 1199–1209 2017 AASLD.


    Date de mise en ligne : Lundi 21 aot 2017
    Manuel Mendizabal, Marcelo O. Silva
    Developing multicenter consortia in liver disease in Latin America: Challenges and opportunities
    The development of consortia has been useful for exploring challenging scenarios and uncharted territories in liver disease treatments. Several consortia already developed in the United States and Europe have become key factors in patient care decision‐making processes and medical education, and they have also impacted policy makers' decisions. In Latin America, the situation is different. As a result of a combination of different factors, our region has not been able to develop networking advantages in research and education in liver diseases. Thus far, most of the initial experiences focused on the development of collaborative groups established to investigate a particular topic, which were dissolved once the questions were answered. It is the aim of this review to describe those difficulties we confront in developing multicenter liver consortia in Latin America, to identify those challenges we face, and also to describe the opportunities we have for improvement. Liver Transplantation 23 1210–1215 2017 AASLD.


    Date de mise en ligne : Lundi 21 aot 2017
    Avegail Flores, Sumeet K. Asrani
    The donor risk index: A decade of experience
    In 2006, derivation of the donor risk index (DRI) highlighted the importance of donor factors for successful liver transplantation. Over the last decade, the DRI has served as a useful metric of donor quality and has enhanced our understanding of donor factors and their impact upon recipients with hepatitis C virus, those with low Model for End‐Stage Liver Disease (MELD) score, and individuals undergoing retransplantation. DRI has provided the transplant community with a common language for describing donor organ characteristics and has served as the foundation for several tools for organ risk assessment. It is a useful tool in assessing the interactions of donor factors with recipient factors and their impact on posttransplant outcomes. However, limitations of statistical modeling, choice of donor factors, exclusion of unaccounted donor and geographic factors, and the changing face of the liver transplant recipient have tempered its widespread use. In addition, the DRI was derived from data before the MELD era but is currently being applied to expand the donor pool while concurrently meeting the demands of a dynamic allocation system. A decade after its introduction, DRI remains relevant but may benefit from being updated to provide guidance in the use of extended criteria donors by accounting for the impact of geography and unmeasured donor characteristics. DRI could be better adapted for recipients with nonalcoholic fatty liver disease by examining and including recipient factors unique to this population. Liver Transplantation 23 1216–1225 2017 AASLD.


    Date de mise en ligne : Lundi 21 aot 2017
    Carmen Cepeda‐Franco, Luis Miguel Marín‐Gómez, Carmen Bernal‐Bellido, Gonzalo Suárez‐Artacho, Jose María Álamo‐Martínez, Francisco Javier Padillo‐Ruiz, Miguel Ángel Gómez‐Bravo
    Alternative outflow reconstruction in domino liver transplantation
    1228


    Date de mise en ligne : Lundi 21 aot 2017
    Tiong Yeng Lim, Iona Coltart, Pierre Foskett, Richard Thompson, Sandra Strautnieks, Leonie Penna, Catherine Williamson, Rosa Miquel, Michael A. Heneghan
    Donor transmitted mutation of the ABCB11 gene and ensuing intrahepatic cholestasis of pregnancy in a liver transplant recipient
    1232


    Date de mise en ligne : Lundi 21 aot 2017
    Marina Serper, Michael S. Wolf
    Is liver transplant education patient‐centered?
    1234


    Date de mise en ligne : Lundi 21 aot 2017
    Erratum: A 10‐year united network for organ sharing review of mortality and risk factors in young children awaiting liver transplantation
    Erratum: A 10‐year united network for organ sharing review of mortality and risk factors in young children awaiting liver transplantation
    1235


    Date de mise en ligne : Lundi 21 aot 2017
    Issue Information
    Issue Information
    1243