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Les derniers abstracts de la revue Liver Transplantation :

    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
    M.H. Doshi, J. Salsamendi, G. Narayanan
    Portal Venous Stenosis Following Liver Transplant: Role of Transsplenic Intervention

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

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

    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 : Mercredi 19 juillet 2017
    Jorge A. Marrero, Amit G. Singal
    Direct‐Acting Antivirals and Recurrence of Hepatocellular Carcinoma

    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

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

    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 : Mercredi 12 juillet 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

    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

    Date de mise en ligne : Vendredi 07 juillet 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 two objectives: (i) determine risk factors for "early" hospitalization (i.e., within 6 months of LT) (ii) quantify the importance of hospitalization history in the first 6 months with respect to subsequent patient survival (i.e., survival, conditional on surviving 6 months post‐LT). Methods: 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 = 7,220). Results: The early hospitalization rate was 2.76 per patient‐year and was significantly associated with many recipient factors (e.g., recipient age, hepatitis C, diabetes, poor renal function including dialysis and recipient of TIPSS procedure before LT), as well as donor race and donation after cardiac death (DCD). Conditional on surviving 6 months post‐LT, the covariate‐adjusted death rate increased by 22% for each additional hospitalization occurring in the first 6 months (HR=1.22; p<0.001). Conclusions: 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 towards identifying LT recipients at risk for early hospitalization and modifying the actionable risk factors such as hepatitis C, diabetes and BMI to improve resource utilization and overall outcomes. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Vendredi 07 juillet 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
    Objective: To evaluate the utility of preoperative needle biopsy (PNB) grading of hepatocellular carcinoma (HCC) as a biomarker for liver transplant (LT) candidate selection. Background: Given the prognostic significance of HCC tumor grade, PNB grading has been proposed as a biomarker for LT candidate selection. Methods: Clinicopathologic characteristics of HCC LT recipients (1989‐2014) with a PNB were analyzed, and 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. Results: 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 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%). Conclusions: 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 to the Milan criteria alone. Incorporation of PNB to guide transplant candidate selection appears unjustified. This article is protected by copyright. All rights reserved.

    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

    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 : Lundi 26 juin 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
    Introduction: The outcomes of liver transplantation from donation after cardiac death (DCD) donors remain poor due to the severe warm ischemic injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD liver transplantation was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia‐reperfusion injury (IRI) and survival after DCD liver transplantation was investigated. Material and Methods: 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. Experiment I: In a 30‐min donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. Experiment II: In a 50‐min donor warm ischemia model, the postoperative survival was assessed. Results: 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. Experiment II: The postoperative survival rate was significantly improved in the PFC group. 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 liver transplantation. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 26 juin 2017
    John O'Grady
    Con: Acute‐on‐Chronic Liver Failure

    Date de mise en ligne : Lundi 26 juin 2017
    M.W. Ross, M Cescon, R Angelico, E Andorno, G Rossi, A Pinna, L De Carlis, U Baccarani, U Cillo, M Colledan, V Mazzaferro, G Tisone, M Rossi, F Tuzzolino, D Pagano, S Gruttadauria, G Mazariegos, B Gridelli, M Spada
    A Matched Pair Analysis of Multicenter Long‐term Follow‐up after Split Liver Transplantation with Extended Right Grafts
    Split liver transplantation has been proposed as an alternative to whole liver transplantation to expand the donor pool, but studies comparing adult long‐term outcomes between the two methods are conflicting and limited. This is the first Italian multicenter study that retrospectively analyzed 119 matched‐pair recipients of whole and extended right grafts for long‐term survival outcomes. In the overall population, whole liver recipients showed higher patient survival at one‐ (93% vs. 73%), five‐ (87% vs. 65%) and ten‐year (83% vs. 60%) after transplantation compared to split liver recipients (p<0.001); graft survivals of whole liver recipients were also superior at one‐ (90% vs. 76%), five‐ (84% vs. 57%) and ten‐year (81% vs. 52%) post‐transplant (p < 0.001). However, among the 81 matched‐pairs that survived the first post‐transplant year, five‐ and ten‐year patient survivals were 90% and 81% for split recipients and 99% and 96% for whole recipients, respectively (p = 0.34). Five‐ and ten‐year graft survivals were also comparable: 87% and 77% for split recipients, and 86% and 82% for whole recipients (p = 0.86). Cox regression analysis identified donor age >50, donor‐to‐recipient weight ratio <1, re‐transplantation status and UNOS I‐IIA status as risk factors for partial graft use. There were no significant differences in five‐year outcomes based on center volume. In conclusion, we demonstrate that adult liver transplantation with extended right grafts can achieve long‐term success comparable to that of whole grafts in appropriate patients but should be selectively used in patients with risk factors. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 26 juin 2017
    Ka Wing Ma, Kenneth S H Chok, Albert Chi Yan Chan, Henry Shiu Cheung Tam, Jeff Wing Chiu Dai, Tan To Cheung, James Yan Yue Fung, Chung Mau Lo
    A New Formula for Estimation of Standard Liver Volume Using Computed Tomography Measured Body Thickness
    Objective To derive a more accurate and easy to use formula for estimation of standard liver volume (ESLV) using novel CT measured parameters Background New formulae for ESLV have been emerging and aiming to improve the accuracy of estimation. However, many of these formulae contain body surface area and logarithm in the equation which lead to more complicated calculation. In addition, substantial error in the estimation of liver volume using these old formulae had been shown. Improved version of formula for ESLV is awaited. Methods This is a retrospective cohort of consecutive living donor liver transplantation from 2005‐2016. Donors were randomly assigned to either formula derivation and validation group. Total liver volume (TLV) measured by CT was used as reference for linear regression analysis against various patient factors. Derived formula was compared with existing formulae. Results There were 722 patients (197 from derivation group, 164 from validation group, and 361 from recipient group) involved in the study. Donor's body weight (P<0.01, OR 10.42 95%CI 7.25‐13.60) and body thickness (P=0.017, OR 2.00 95% CI 0.36‐3.65) were found to be the independent factors for TLV calculation. A formula for TLV was derived: 2*thickness (mm) +10*weight (kg) +190 with R2 0.48, which was the highest when compared with four other most cited formulae. This formula remained superior to other published formulae in the validation set analysis (R2 5.37 and inter‐class correlation coefficient 0.74). GW/ESLV calculated by the new formula were shown to have highest correlation with delayed graft function (c‐stat 0.79, 95%CI 0.69‐0.90,P<0.01). Conclusion 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 most accurate for ESLV. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 07 juin 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 (LTx‐aGVHD) has a high mortality rate (85%). A gradual decrease in regulatory T cells (T‐regs) correlates with disease progression in a rat LTx‐GVHD model and treatments which increase T‐regs exert therapeutic effects on LTx‐aGVHD. In this study, LTx‐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 T‐reg 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 and 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+Foxp3+ T‐regs. Furthermore, injection of OSI‐027‐induced donor‐derived CD4+CD25+ T cells into the peripheral blood of LTx‐aGVHD model rats prevented LTx‐aGVHD. Thus, OSI‐027 is implicated as a novel method for the treatment of LTx‐aGVHD. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 07 juin 2017
    Manuel Mendizabal, Marcelo O. Silva
    Developing Multicenter Consortia in Liver Disease in Latin America: Challenges and Opportunities
    Developmentof consortiums have been useful for exploringchallengingscenarios and unchartered territoriesin liver diseases. Several consortia already developed in the United States and Europehave become key factors in patient care decision making processes, medical education and also impacting upon 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 take off in terms of networking advantages in research and education in liver diseases. Thus far,most of the initial experiences have focused on the development of collaborative groups established to investigate a particular topic, which were dissolved once the questions have been answered. It is then the aim of this review is to describe those difficulties we confront in developing multicenter liver consortiums in Latin America, to identify those challenges we face and also todescribe the opportunities for improvement we have. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 07 juin 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 three 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. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 07 juin 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 enhanced our understanding of donor factors and their impact upon recipients with hepatitis C, 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, tailored for recipients with nonalcoholic fatty liver disease and account for the impact of geography and unmeasured donor characteristics. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 07 juin 2017
    S. Rademacher, D. Seehofer, D. Eurich, W. Schoening, R. Neuhaus, R. Oellinger, T. Denecke, A. Pascher, E. Schott, M. Sinn, P. Neuhaus, J. Pratschke
    28‐year incidence of de novo malignancies after liver transplantation: A single‐center analysis of risk factors and mortality in 1616 patients
    BACKGROUND: De novo malignancies are one of the leading causes of late mortality after liver transplantation (LT). METHODS: We analyzed 1616 consecutive patients who underwent LT between 1988 and 2006 at our institution. All patients were prospectively observed over a study period of 28 years by our own outpatient clinic. Complete follow up data were available for 96% of patients, 3% were incomplete and only 1% were lost to follow‐up. The median follow‐up of the patients was 14.1 years. Variables with possible prognostic impact on the development of de novo malignancies (DNM) were analyzed, as was the incidence of malignancies compared to the non‐transplant population by using standardized incidence ratios (SIRs). RESULTS: In total 266 patients (16,5%) developed 322 DNM of the following subgroups: hematological malignancies (n: 49), skin cancer (n: 83) and non‐skin solid organ tumors (SOT) (n: 190). The probability of developing any DNM within 10 and 25 years was 12.9% and 23.0%, respectively. The respective probability of developing SOT was 7.8% and 16.2%. Mean age at time of diagnosis of SOT was 57.4 years (range, 18‐82 years). In the multivariate analysis an increased recipient age (HR 1.03, P=0.001) and a history of smoking (HR 1.92, p= 0.001) were significantly associated with development of SOT. Moreover, the development of SOT was significantly increased in cyclosporine A‐ treated compared to tacrolimus‐ treated patients (HR 1.53, P= 0.03). CONCLUSION: The present analysis shows a disproportionate increase of de novo SOT with an increasing follow up period. Increased age and a history of smoking are confirmed as major risk factors. Moreover, the importance of immunosuppression is highlighted. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mardi 23 mai 2017
    Marina Serper, Michael S. Wolf
    In response to: Is Liver Transplant Education Patient‐Centered?

    Date de mise en ligne : Lundi 22 mai 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
    Drop‐out rate from the liver transplant waiting list due to HCC progression in HCV‐infected patients treated with direct acting antivirals
    Background & Aim: concerns about an increased hepatocellular carcinoma (HCC) recurrence rate following directly acting antiviral (DAA) therapy in cirrhotic patients with a prior complete oncological response have been raised. Data regarding the impact of HCV‐treatment with DAAs on waiting list drop‐out rates in patients with active HCC and HCV‐related cirrhosis awaiting liver transplantation (LT) are lacking. Materials and Methods: HCV‐HCC patients listed for LT between January 2015 and May 2016 at Padua Liver Transplant Centre were considered eligible for the study. After enrollment patients were divided into 2 groups, depending on whether they underwent DAAs 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. Results: twenty‐three 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%) drop‐out events due to HCC‐progression were registered (p = 0.9). No significant differences in terms of radiological progression were highlighted (p = 0.16). Nine out of 23 cases (39%) and 14/23 (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 DAAs treated patient (12,5%) and 1/12 control (8,3%) experienced HCC recurrence (p = 0.6). Conclusions: Viral eradication does not seem to be associated with an increased risk of drop‐out due to neoplastic progression in HCV‐HCC patients awaiting LT. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Vendredi 19 mai 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 intra‐hepatic cholestasis of pregnancy in a liver transplant recipient
    In liver transplant (LT) recipients, the cause of graft dysfunction in pregnancy is often difficult to ascertain. Moreover, a liver biopsy in late pregnancy is often avoided as a consequence of patient and physician factors. Management of graft dysfunction can be difficult in this setting. We report a 30‐year‐old female LT recipient who developed acutely deranged liver biochemistry during the third trimester of her first pregnancy. At 29 weeks gestation, her liver function test (LFT) became abnormal; AST peaked at 978 IU/L (normal range 10‐50), GGT 25 IU/L (normal range 1‐55), bilirubin 1.5 mg/dL (normal range 0.3‐1) and serum bile acids 52 µmol/L (normal range <14). Immunosuppression levels were low or undetectable. The patient received empirical high dose methylprednisolone for three days and was induced at 36 weeks gestation. A liver biopsy performed 3 days after delivery was non‐diagnostic other than for the presence of mild cholestatic rosetting. Previously elevated liver enzymes rapidly improved after delivery and were normal within 2 weeks. Next generation sequencing for a panel of genes known to cause genetic cholestasis revealed that the donor carried mutations in the ABCB11 gene; heterozygous for a missense mutation p.Arg698His and homozygous for the ABCB11 modifier variant p.Val444Ala. Whilst not constituting classical bile salt export pump (BSEP) deficiency, these mutations cause reduced canalicular transport of bile products leading to an increased risk of drug‐induced cholestasis, gallstones and cholestasis of pregnancy. This case demonstrates the rare finding of donor‐transmitted risk of intrahepatic cholestasis of pregnancy. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 17 mai 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 (US) per requirements of the Center for Medicare and Medicaid Services. Previous data has shown the Braden Scale can predict both frailty and mortality risk in patients with decompensated cirrhosis. Our aim was to evaluate the association of Braden Scale score with short‐term outcomes after liver transplantation (LT). We performed a retrospective cohort study of deceased‐donor LT recipients at two 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), non‐ambulatory 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, non‐ambulatory status, and discharge to a rehabilitation facility, as compared to 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% CI: 1.47‐1.65), non‐ambulatory status at discharge (OR 4.15;95% CI:1.77‐9.71), and discharge to a rehabilitation facility (OR 5.51;95% CI: 2.57‐11.8). Conclusion: The Braden Scale, which is currently assessed in all hospitalized patients in the US, independently predicted early disability‐related outcomes and greater LOS after LT. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 19 avril 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 long‐term 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. Twenty‐three patients received SMT and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life 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 to 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% VS 0, P = 0.01). Moreover, better quality of life 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 quality of life. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Jeudi 02 fvrier 2017
    Joon‐Young Ohm, Gi‐Young Ko, Kyu‐Bo Sung, Dong‐Il Gwon, Heung‐Gyu Koh
    Safety and efficacy of transhepatic and transsplenic access for endovascular management of portal vein complications after liver transplantation1
    Objective: 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 transplant recipients. Methods: Eighteen 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 was preserved, and the target lesion did not involve confluence of the superior mesenteric and splenic veins. Accessibility of the percutaneous transsplenic puncture was confirmed via ultrasound 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 ultrasound 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. Results: Transhepatic or transsplenic access was successfully achieved in all patients. Twelve patients underwent stent placement; 3, balloon angioplasty only; 2, variceal embolization only; and 1, variceal embolization followed by successful stent placement. Regarding major complications, 1 patient experienced a splenic vein 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. Conclusion: Endovascular management of PV via percutaneous transsplenic access is a relatively safe and effective alternative that does not damage the liver grafts of liver transplant recipients. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 01 avril 2015

    Date de mise en ligne : Mercredi 19 juillet 2017
    Issue Information
    Issue Information

    Date de mise en ligne : Mercredi 19 juillet 2017
    Sunil Taneja, Yogesh K. Chawla
    Perioperative use of terlipressin in adult liver transplant

    Date de mise en ligne : Mercredi 19 juillet 2017
    Adam D. Griesemer, Jean C. Emond
    Big improvements for the smallest recipients

    Date de mise en ligne : Mercredi 19 juillet 2017
    Jae Geun Lee, Kwang‐Woong Lee, Choon Hyuck David Kwon, Chong Woo Chu, Bong‐Wan Kim, Dong Lak Choi, Young Kyoung You, Dong‐Sik Kim, Yang Won Nah, Koo Jeong Kang, In Soek Choi, Hee Chul Yu, Geun Hong, Ho‐Seong Han, Shin Hwang, Myoung Soo Kim
    Donor safety in living donor liver transplantation: The Korean organ transplantation registry study
    Major concerns about donor safety cause controversy and limit the use of living donor liver transplantation to overcome organ shortages. The Korean Organ Transplantation Registry established a nationwide organ transplantation registration system in 2014. We reviewed the prospectively collected data of all 832 living liver donors who underwent procedures between April 2014 and December 2015. We allocated the donors to a left lobe group (n = 59) and a right lobe group (n = 773) and analyzed the relations between graft types and remaining liver volumes and complications (graded using the Clavien 5‐tier grading system). The median follow‐up was 19 months (range, 10‐31 months). During the study period, 553 men and 279 women donated livers, and there were no deaths after living liver donation. The overall, biliary, and major complication (grade ≥ III) rates were 9.3%, 1.7%, and 1.9%, respectively. The graft types and remaining liver volume were associated with significantly different overall, biliary, and major complication rates. Of the 16 patients with major complications, 9 (56.3%) involved biliary complications (2 biliary strictures [12.5%] and 7 bile leakages [43.8%]). Among the 832 donors, the mean aspartate transaminase, alanine aminotransferase, and total bilirubin levels were 23.9 ± 8.1 IU/L, 20.9 ± 11.3 IU/L, and 0.8 ± 0.4 mg/dL, respectively, 6 months after liver donation. In conclusion, biliary complications were the most common types of major morbidity in living liver donors. Donor hepatectomy can be performed successfully with minimal and easily controlled complications. Our study shows that prospective, nationwide cohort data provide an important means of investigating the safety in living liver donation. Liver Transplantation 23 999–1006 2017 AASLD.

    Date de mise en ligne : Jeudi 29 juin 2017
    Mettu Srinivas Reddy, Ilankumaran Kaliamoorthy, Akila Rajakumar, Selvakumar Malleeshwaran, Ellango Appuswamy, Sukanya Lakshmi, Joy Varghese, Mohamed Rela
    Double‐blind randomized controlled trial of the routine perioperative use of terlipressin in adult living donor liver transplantation
    Perioperative terlipressin (Tp) during living donor liver transplantation (LDLT) has been shown to reduce intraoperative portal pressures and improve renal function. Its role and safety profile have never been evaluated in a double‐blind randomized controlled trial (RCT). The aim was to evaluate the hemodynamic effects, clinical benefits, and safety of perioperative Tp infusion in adult LDLT. This was a single‐center double‐blind RCT. Consenting adults with chronic liver disease and low risk of posttransplant renal dysfunction undergoing their first LDLT were randomized. The study group (terlipressin group [TpG]) received an initial bolus of Tp during surgery followed by a Tp infusion for 72 hours in the postoperative period. The placebo group (PbG) received a saline infusion. The primary endpoint was portal pressure after arterial reperfusion. Multiple intraoperative and postoperative variables served as secondary endpoints. A total of 41 patients were enrolled in the trial (TpG, 21; PbG, 20). There were no significant differences in intraoperative portal pressures, blood loss, fluid requirement, vasopressor requirement, or urine output. Peak intraoperative and end of surgery lactate levels were significantly higher in the Tp group. There was no difference in postoperative liver function tests. Incidence of acute kidney injury as assessed by Risk, Injury, Failure, Loss, and End‐Stage Kidney Disease criteria was lower in the Tp group (27% versus 60%; P = 0.04). The TpG had less postoperative ascites, a lower need for percutaneous interventions, and a shorter hospital stay. Incidence of bradycardia requiring pharmacological intervention and withdrawal from study was significantly higher in the TpG. In conclusion, this study has not demonstrated a reduction in postreperfusion portal pressure with Tp. However, Tp infusion reduced postoperative ascitic drain output resulting in less frequent percutaneous interventions and reduced hospital stay. Intraoperative hyperlactatemia and symptomatic bradycardia are major concerns. Its use should be restricted to patients with high‐volume ascites, and it needs close monitoring during drug infusion. Liver Transplantation 23 1007–1014 2017 AASLD.

    Date de mise en ligne : Lundi 26 juin 2017
    Sara M. Lewin, Neil Mehta, R. Kate Kelley, John P. Roberts, Francis Y. Yao, Danielle Brandman
    Liver transplantation recipients with nonalcoholic steatohepatitis have lower risk hepatocellular carcinoma
    Liver transplantation (LT) is a well‐established treatment for hepatocellular carcinoma (HCC) in carefully selected patients. Risk factors for tumors with poor prognostic features on explant have not been well described in a national cohort. We performed a retrospective cohort study of adult LT recipients with HCC transplanted from April 8, 2012 (when explant pathology in United Network for Organ Sharing [UNOS] became available) until September 30, 2014. We evaluated the association between listing diagnosis and other demographic factors with tumor features on explant using logistic regression. High‐risk tumor features included the following: > 3 tumors, largest tumor > 5 cm, presence of vascular invasion, presence of metastases, and poor differentiation of tumor. In total, 3733 LT recipients with HCC who had complete explant data in UNOS were included. The median age was 60 years; 78% were male; and 68% were white. Of the primary non‐HCC listing diagnoses, 2608 (70%) had hepatitis C virus (HCV); 271 (7%) had nonalcoholic steatohepatitis (NASH); 246 (7%) had alcoholic cirrhosis; and 189 (5%) had hepatitis B virus. Also, 1140 (31%) had evidence of ≥ 1 high‐risk explant feature(s). The presence of ≥ 1 high‐risk explant feature(s) was associated with HCC recurrence after transplant (odds ratio [OR], 5.00; P < 0.001). Compared with HCV‐associated HCC transplant recipients, individuals with NASH had lower likelihood of high‐risk explant features (OR, 0.71; P = 0.02) after adjusting for covariables. Women were more likely to have high‐risk explant features (OR, 1.23; P = 0.04). Diabetes mellitus (DM) was not associated with high‐risk explant features. In conclusion, LT recipients with NASH‐associated HCC had fewer high‐risk tumor features on explant compared with HCV‐associated HCC, despite having higher rates of DM and other potential risk factors for the development of HCC. Women had a higher likelihood of high‐risk tumor features. Further study is warranted whether these differences are due to disease‐specific or sex‐specific influences on tumor biology or due to selection criteria for transplant. Liver Transplantation 23 1015–1022 2017 AASLD.

    Date de mise en ligne : Lundi 03 juillet 2017
    Ho Joong Choi, Dong Goo Kim, Gun Hyung Na, Tae Ho Hong, Si Hyun Bae, Young Kyoung You, Jong Young Choi, Seung Kew Yoon
    The clinical outcomes of patients with portal vein tumor thrombi after living donor liver transplantation
    The purpose of this study was to evaluate the feasibility of living donor liver transplantation for treatment of patients with hepatocellular carcinoma and segmental portal vein tumor thrombus (PVTT) below the second‐order branch. Between January 2005 and December 2015, we retrospectively analyzed 242 patients in a control group (n = 184), a microvascular invasion (MVI) group (n = 24), and a PVTT group (n = 34). To assess the risks associated with PVTT, we evaluated recurrence, the disease‐free survival (DFS) rate, the overall survival (OS) rate, and various other factors based on the characteristics of patients and tumors. Of the 242 patients, 5‐year DFS and OS rates were 79.5% and 70.7%. A total of 34 (14.0%) patients had PVTT, of whom 7 had lobar PVTT in first‐order branches. The control, MVI, and PVTT groups significantly differed in terms of tumor morphology (maximal and total diameters) and biology (alpha‐fetoprotein [AFP] and protein induced by vitamin K absence or antagonist II). The control, MVI, and PVTT groups significantly differed in terms of the recurrence, DFS, and OS rates. Especially, lobar PVTT reduced the 5‐year DFS and OS rates to dismal and 14.3%, respectively, but segmental PVTT was associated with favorable 5‐year DFS and OS rates (63.9% and 50.3%, respectively). We found no statistically significant difference in the DFS and OS rates of patients with MVI alone and segmental PVTT alone. In patients in the segmental PVTT group with AFP levels of <100 ng/mL, the 5‐year DFS and OS rates were 90.9% and 71.3%, respectively. In conclusion, a tumor thrombus in a lobar portal vein remains a contraindication to liver transplantation. However, a segmental PVTT is acceptable, especially when the AFP level is <100 ng/mL. Liver Transplantation 23 1023–1031 2017 AASLD.

    Date de mise en ligne : Mercredi 19 juillet 2017
    Mark Draoua, Nicole Titze, Amar Gupta, Hoylan T. Fernandez, Michael Ramsay, Giovanna Saracino, Gregory McKenna, Giuliano Testa, Goran B. Klintmalm, Peter T. W. Kim
    Significance of measured intraoperative portal vein flows after thrombendvenectomy in deceased donor liver transplantations with portal vein thrombosis
    Adequate portal vein (PV) flow in liver transplantation is essential for a good outcome, and it may be compromised in patients with portal vein thrombosis (PVT). This study evaluated the impact of intraoperatively measured PV flow after PV thrombendvenectomy on outcomes after deceased donor liver transplantation (DDLT). The study included 77 patients over a 16‐year period who underwent PV thrombendvenectomy with complete flow data. Patients were classified into 2 groups: high PV flow (>1300 mL/minute; n = 55) and low PV flow (≤1300 mL/minute; n = 22). Postoperative complications and graft survival were analyzed according to the PV flow. The 2 groups were similar in demographic characteristics. Low PV flow was associated with higher cumulative rates of biliary strictures (P = 0.02) and lower 1‐, 2‐, and 5‐year graft survival (89%, 85%, and 68% versus 64%, 55%, and 38%, respectively; P = 0.002). There was no difference in the incidence of postoperative PVT between the groups (1.8% versus 9.1%; P = 0.19). No biliary leaks or hepatic artery thromboses were reported in either group. By multivariate analyses, age >60 years (hazard ratio [HR], 3.04, 95% confidence interval [CI], 1.36‐6.82; P = 0.007) and low portal flow (HR, 2.31; 95% CI, 1.15‐4.65; P = 0.02) were associated with worse survival. In conclusion, PV flow <1300 mL/minute after PV thrombendvenectomy for PVT during DDLT was associated with higher rates of biliary strictures and worse graft survival. Consideration should be given to identifying reasons for low flow and performing maneuvers to increase PV flow when intraoperative PV flows are <1300 mL/minute. Liver Transplantation 23 1032–1039 2017 AASLD.

    Date de mise en ligne : Mercredi 19 juillet 2017
    Neda Milosavljevic, Marina Gazdic, Bojana Simovic Markovic, Aleksandar Arsenijevic, Jasmin Nurkovic, Zana Dolicanin, Valentin Djonov, Miodrag L. Lukic, Vladislav Volarevic
    Mesenchymal stem cells attenuate acute liver injury by altering ratio between interleukin 17 producing and regulatory natural killer T cells
    Mesenchymal stem cells (MSCs) are, due to immunomodulatory characteristics, considered as novel agents in the treatment of immune‐mediated acute liver failure. Although it is known that MSCs can regulate activation of T lymphocytes, their capacity to modulate function of neutrophils and natural killer T (NKT) cells, major interleukin (IL) 17–producing cells in acute liver injury, is still unknown. By using 2 well‐established murine models of neutrophil and NKT cell–mediated acute liver failure (induced by carbon tetrachloride and α‐galactoceramide), we investigated molecular and cellular mechanisms involved in MSC‐mediated modulation of IL17 signaling during acute liver injury. Single intravenous injection of MSCs attenuate acute hepatitis and hepatotoxicity of NKT cells in a paracrine, indoleamine 2,3‐dioxygenase (IDO)–dependent manner. Decreased levels of inflammatory IL17 and increased levels of immunosuppressive IL10 in serum, reduced number of interleukin 17–producing natural killer T (NKT17) cells, and increased presence of forkhead box P3 + IL10–producing natural killer T regulatory cells (NKTregs) were noticed in the injured livers of MSC‐treated mice. MSCs did not significantly alter the total number of IL17‐producing neutrophils, CD4+, and CD8 + T lymphocytes in the injured livers. Injection of mesenchymal stem cell–conditioned medium (MSC‐CM) resulted with an increased NKTreg/NKT17 ratio in the liver and attenuated hepatitis in vivo and significantly reduced hepatotoxicity of NKT cells in vitro. This phenomenon was completely abrogated in the presence of IDO inhibitor, 1‐methyltryptophan. In conclusion, the capacity of MSCs to alter NKT17/NKTreg ratio and suppress hepatotoxicity of NKT cells in an IDO‐dependent manner may be used as a new therapeutic approach in IL17‐driven liver inflammation. Liver Transplantation 23 1040–1050 2017 AASLD.

    Date de mise en ligne : Lundi 03 juillet 2017
    Mureo Kasahara, Seisuke Sakamoto, Kengo Sasaki, Hajime Uchida, Toshihiro Kitajima, Takanobu Shigeta, Soichi Narumoto, Yoshihiro Hirata, Akinari Fukuda
    Living donor liver transplantation during the first 3 months of life
    Living donor liver transplantation (LDLT) is now an established technique for treating children with end‐stage liver disease. Few data exist about liver transplantation (LT) for exclusively young infants, especially infants of <3 months of age. We report our single‐center experience with 12 patients in which LDLT was performed during the first 3 months of life and compare the results with those of older infants who underwent LT. All of the patients were treated at the National Center of Child Health and Development, Tokyo, Japan. Between November 2005 to November 2016, 436 children underwent LT. Twelve of these patients underwent LT in the first 3 months of life (median age, 41 days; median weight, 4.0 kg). The indications for transplantation were fulminant hepatic failure (n = 11) and metabolic liver disease (n = 1). All the patients received the left lateral segment (LLS) in situ to mitigate the problem of graft‐to‐recipient size discrepancy. A reduced LLS graft was used in 11 patients and a segment 2 monosegment graft was used in 1 patient. We compared the results with those of infants who were 4‐6 months of age (n = 67) and 7‐12 months of age (n = 110) who were treated in the same study period. There were significant differences in the Pediatric End‐Stage Liver Disease score and the conversion rate of tacrolimus to cyclosporine in younger infants. Furthermore, the incidence of biliary complications, bloodstream infection, and cytomegalovirus infection tended to be higher, whereas the incidence of acute cellular rejection tended to be lower in younger infants. The overall cumulative 10‐year patient and graft survival rates in recipients of <3 months of age were both 90.9%. LDLT during the first 3 months of life appears to be a feasible option with excellent patient and graft survival. Liver Transplantation 23 1051–1057 2017 AASLD.

    Date de mise en ligne : Lundi 03 juillet 2017
    Carlos Moctezuma‐Velazquez, Sylvia Kalainy, Juan G. Abraldes
    Beta‐blockers in patients with advanced liver disease: Has the dust settled?
    Nonselective beta‐blockers (NSBBs) have been the backbone for the treatment of portal hypertension in cirrhosis for the last 3 decades. A publication in 2010 of a prospective observational study suggested that NSBBs could increase mortality in patients with refractory ascites. This opened a controversy about the safety and efficacy of NSBBs in patients with advanced liver disease and led to the publication of a large corpus of observational data assessing the safety of NSBBs in patients with advanced cirrhosis. In this article, we briefly review the clinical pharmacology of NSBBs, the pathophysiological basis for the underlying benefits and harms of NSBBs in advanced cirrhosis, and the evidence in favor and against the use of NSBBs in specific scenarios. Finally, we summarize the current recommendations and propose areas of opportunity for future research. Liver Transplantation 23 1058–1069 2017 AASLD.

    Date de mise en ligne : Lundi 03 juillet 2017
    Yanik J. Bababekov, Zhi Fong, David C. Chang, Mary Ann Simpson, Heidi Yeh, James J. Pomposelli
    Is liver transplant education patient‐centered?

    Date de mise en ligne : Mercredi 19 juillet 2017
    Christian Toso, Hugo Pinto Marques, Axel Andres, Francisco Castro Sousa, René Adam, Antonio Kalil, Pierre‐Alain Clavien, Emanuel Furtado, Eduardo Barroso, Henri Bismuth,
    Liver transplantation for colorectal liver metastasis: Survival without recurrence can be achieved

    Date de mise en ligne : Mercredi 19 juillet 2017
    Kyung‐Suk Suh, Hyo‐Sin Kim, Nam‐Joon Yi, Kwang‐Woong Lee, Suk Kyun Hong, Kyung Chul Yoon, Adianto Nugroho, Hyeyoung Kim
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