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Les derniers abstracts de la revue Liver Transplantation :

    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 : Lundi 22 mai 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 colo‐rectal liver metastasis: Survival without recurrence can be achieved

    Date de mise en ligne : Vendredi 19 mai 2017
    Emer Fitzpatrick, Maesha Deheragoda, Anil Dhawan
    Allograft steatosis in the midst of the epidemic of obesity; are children in the honeymoon period?

    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 : Mardi 16 mai 2017
    Thomas Reiberger, Jonel Trebicka
    New liver – fresh microbiome: Implications on brain function

    Date de mise en ligne : Lundi 15 mai 2017
    Matthew H. Levine, Tatiana Akimova, Douglas R. Murken, Wayne W Hancock
    Regulatory T Cell Signatures in Liver Transplant Recipients Successfully Weaned from Immunosuppression: Getting from Here to There

    Date de mise en ligne : Lundi 08 mai 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 IL‐17 producing and regulatory NKT 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 NKT cells, major interleukin (IL)‐17 producing cells in acute liver injury, is still unknown. By using two well established murine models of neutrophil and NKT cell mediated acute liver failure (induced by Carbon tetrachloride (CCl4) and alphagalactoceramide (α‐GalCer)), we investigated molecular and cellular mechanisms involved in MSC‐mediated modulation of IL‐17 signaling during acute liver injury. Single intravenous injection of MSCs attenuate acute hepatitis and hepatotoxicity of NKT cells in paracrine, indoleamine 2,3‐dioxygenase (IDO)‐dependent manner. Decreased levels of inflammatory IL‐17 and increased levels of immunosuppressive IL‐10 in serum, reduced number of IL‐17 producing NKT (NKT17) cells and increased presence of FoxP3+ IL‐10 producing NKT regulatory (NKTreg) cells were noticed in the injured livers of MSC‐treated mice. MSCs did not significantly alter total number of IL‐17‐producing neutrophils, CD4+ and CD8+ T lymphocytes in the injured livers. Injection of MSC conditioned medium (MSC‐CM) resulted with 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. Conclusion. The capacity of MSCs to alter NKT17/NKTreg ratio and suppress hepatotoxicity of NKT cells in IDO dependent manner may be used as new therapeutic approach in IL‐17 driven liver inflammation. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 08 mai 2017
    Hyeyoung Kim, Kyung Chul Yoon, Kwang‐Woong Lee, Nam‐Joon Yi, Hae Won Lee, YoungRok Choi, Dongkyu Oh, Hyo‐Sin Kim, Suk Kyun Hong, Sung Woo Ahn, Kyung‐Suk Suh
    Tips and Pitfalls in Direct Ligation of Large Spontaneous Splenorenal Shunt during Liver Transplantation
    Patients with large spontaneous splenorenal shunt (SRS) prove challenging during liver transplantation (LT), irrespective of organizing portal vein (PV) thrombosis. Here, we detail the clinical outcomes of 26 patients who underwent direct ligation of large SRS during LT. Direct ligation of large SRS was applied in poor portal flow during LT. We performed temporary test clamping of the SRS before direct ligation and applied PV pressure monitoring in patients who showed signs of portal hypertension, such as bowel edema. We retrospectively reviewed and evaluated their clinical outcomes. Among 843 patients who underwent LT between 2010 and 2015, 26 (3.9%) underwent direct ligation of SRS without any intraoperative event. Mean preoperative MELD score was 16.7±9.0. The main PV diameter on preoperative computed tomography was 8.3±3.4 mm (range, 3.0‐14.0 mm). SRS was easily identified at just below the distal pancreas and beside the inferior mesenteric vein in all patients. Accompanying PV thrombectomy was done in 42.3% of patients. Among 26 patients, massive and prolonged ascites was evident in 15.4% (n = 4) postoperatively. They were all living donor LT recipients with a small PV diameter (4.0‐6.7 mm). Except for one patient who underwent splenic artery embolization, ascites was tolerable and well controlled by conservative management. There was a 7.7% rate of major complications related to direct ligation, including reoperation due to combined ligation of SRS along with a left renal vein at the confluence. Except for one hospital mortality due to sepsis, 25 patients (96.2%) are alive with no evidence of further PV complications. In conclusion, direct ligation of large SRS during LT is a safe and feasible method to overcome the effects of a large SRS. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 08 mai 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
    Introduction: The purpose of this study was to evaluate the feasibility of living‐donor liver transplantation (LDLT) for treatment of patients with hepatocellular carcinoma (HCC) and segmental portal vein tumor thrombi (PVTT) below the second‐order branch. Patients and Methods: 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 rate (DFS), the overall survival rate (OS), and various other factors based on the characteristics of patients and tumors. Results: Of the 242 patients, 5‐year DFS and OS rates were 79.5% and 70.7%. Thirty‐four (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 (AFP and PIVKA‐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 were 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 rate of patients with MVI alone and segmental PVTT alone. In patients in the segmental PVTT group with AFP levels < 100 ng/mL, the 5‐year DFS and OS rates were 90.9% and 71.3%, respectively. 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. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Samedi 06 mai 2017
    Arnaud Del Bello, Nicolas Congy‐Jolivet, Benoit Audry, Corinne Antoine, Laure Esposito, Anne‐Laure Hebral, Nassim Kamar
    Impact of transplant accessibility for sensitized patients by avoiding unacceptable antigens
    Recent data have confirmed the negative impact of preformed donor‐specific antibodies after liver transplantation. In order to reduce the risk of developing lesions associated with acute and chronic antibody‐mediated rejection in liver‐transplant recipients, we evaluated the consequences in terms of transplant accessibility, associated with avoiding preformed DSAs according to several MFI‐titer thresholds that have been previously reported to be relevant in liver transplantation. Among the 484 included LT candidates, 99 (20.5%) presented anti‐HLA antibodies. the predictive factors for anti‐HLA sensitization were a history of previous kidney transplantation [OR 1.5; 95%CI: 1.30‐1.9, p= 0.05], a history of previous liver transplantation [OR 1.9; 95%CI: 1.6‐2.1, p= 0.01], a history of blood transfusion [OR 2.5, 95%CI: 2.2‐4.1, p= 0.01], and a history of pregnancy [OR 2.9, 95%CI: 2.4‐3.3, p= 0.04]. By applying a strategy of unacceptable mismatches for recipients with an Ab MFI of >5000, only 35 patients were affected (7% of the cohort), but 22 of these (61%) would have been considered incompatible with >50% of the donors. Using a MFI threshold of >10,000, only 16 patients were affected (1.4% of the cohort), but half of these would have been considered incompatible with >50% of the proposed donors. Considering only those with anti‐class II Ab and a MFI >5,000 and >10,000, respectively, 10/14 and 4/8 patients that were considered incompatible with >50% of the donors. Conclusion: avoiding preformed DSAs affects a small but not negligible proportion of liver‐transplant candidates. However, in these sensitive patients, avoiding preformed DSAs has the potential to significantly reduce the donor pool and consequently the transplant accessibility. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Vendredi 21 avril 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 (KOTRY) 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 live 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 five‐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 live 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 cases with major complications, nine (56.3%) involved biliary complications [two biliary strictures (16.5%) and seven bile leakages (43.8%)]. Among the 832 donors, the mean AST, ALT, 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 live 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 live liver donation. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Jeudi 20 avril 2017
    Emily R. Perito, Tabitha Vase, Rageshree Ramachandran, Andrew Phelps, Kuang‐Yu Jen, Robert H. Lustig, Vickie A. Feldstein, Philip Rosenthal
    Hepatic steatosis after pediatric liver transplant
    Rationale: Hepatic steatosis develops after liver transplant in 30% of adults, and non‐alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in non‐transplanted children. However, post‐transplant steatosis has been minimally studied in pediatric liver transplant recipients. We explored the prevalence, persistence, and association with chronic liver damage of hepatic steatosis in these children. Results: In this single‐center study of pediatric patients transplanted 1988‐2015 (n=318), 31% of those with any post‐transplant biopsy (n=271) had ≥1 biopsy with steatosis. Median time from transplant to first biopsy with steatosis was 0.8 months (IQR 0.3‐6.5) and to last biopsy with steatosis was 5.5 months (IQR 1.0‐24.5). 85% of patients with steatosis also had for‐cause biopsies without steatosis. All available for‐cause biopsies were re‐evaluated (n=104); Of 9 biopsies that could be interpreted as NASH/Borderline NASH, with steatosis plus inflammation or ballooning, 8 also had features of cholestasis or rejection. Among 70 patients with surveillance biopsies 3.6‐20.0 years post‐transplant, only 1 overweight adolescent had a biopsy with NAFLD (grade 1 steatosis, mild inflammation, no ballooning or fibrosis)—despite a 30% prevalence of overweight/obesity in the cohort and 27% with steatosis on previous for‐cause biopsy. Steatosis on preceding for‐cause biopsy was not associated with portal (p=0.49) or perivenular fibrosis (p=0.85) on surveillance biopsy. Conclusions: Hepatic steatosis commonly develops early post‐transplant in children and adolescents, but it rarely persists. Biopsies that did have steatosis with NASH characteristics were all for‐cause, mostly in patients with NAFLD risk factors and/or confounding causes of liver damage. Prospective studies that follow children into adulthood will be needed to evaluate if and when hepatic steatosis presents a long‐term risk for pediatric liver transplant recipients. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Jeudi 20 avril 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 Transplants with Portal Vein Thrombosis
    Background: 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. Study Design: The study included 77 patients over a 16‐year period who underwent PV thrombendvenectomy with complete flow data. Patients were classified into two groups: high PV flow (>1300 mL/min, N = 55) and low PV flow (≤1300 mL/min, N = 22). Postoperative complications and graft survival were analyzed according to the PV flow. Results: The two groups were similar in demographic characteristics. Low PV flow was associated with higher cumulative rates of biliary strictures (P = 0.016) and lower 1‐, 2‐, and 5‐year graft survival (89%, 85%, and 68% vs. 64%, 55%, and 38%, respectively, P = 0.002). There was no difference in the incidence of postoperative PVT between the groups (1.8% vs. 9.2%, P = 0.19). No biliary leaks or hepatic artery thromboses were reported in either group. By multivariate analyses, age >60 years (hazard ratio 3.04, confidence interval 1.36‐6.82; P = 0.007) and low portal flow (HR 2.31 (1.15‐4.65, P=0.02) were associated with worse survival. Conclusion: PV flow <1300 mL/min after PV thrombendvenectomy for PVT during deceased donor liver transplantation 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/min. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 19 avril 2017
    Silvia Martini, Francesco Tandoi, Lodovico Terzi di Bergamo, Silvia Strona, Bruna Lavezzo, Marco Sacco, Francesca Maione, Federica Gonella, Paolo Strignano, Dominic Dell Olio, Mauro Salizzoni, Giorgio Maria Saracco, Renato Romagnoli
    Negativization of viremia prior to liver transplant reduces early allograft dysfunction in hepatitis C recipients
    Although early allograft dysfunction (EAD) negatively impacts on survival from the first months following liver transplantation (LT), direct‐acting antivirals (DAAs) have revolutionized HCV therapy. We investigated the EAD definition best predicting 90‐day graft loss and identified EAD risk factors in HCV positive recipients. From 11‐2002 to 06‐2016, 603 HCV‐positive patients (hepatocellular carcinoma 53.4%) underwent a first LT with HCV‐negative donors. Median recipient MELD score 15, median donor age 63 years. At LT, 77 (12.8%) patients were HCV RNA negative; negativization was achieved and maintained by pre‐LT antiviral therapy (61 patients) or pre‐LT+pre‐emptive post‐LT course (16 patients); 60 (77.9%) patients received DAAs and 17 (22.1%) interferon. We compared three different EAD definitions: a) bilirubin≥10 mg/dL or INR≥1.6 on day 7 post‐LT or AST or ALT>2000 IU/L within 7 days of LT; b) bilirubin>10 mg/dL on days 2 to 7 post‐LT; c) MELD≥19 on day 5 post‐LT. EAD defined by MELD≥19 on day 5 post‐LT had the lowest negative (0.1) and the highest positive (1.9) likelihood ratio to predict 90‐day graft loss. At 90 days post‐LT, 9.2% of recipients with EAD lost their graft as opposed to 0.7% of those without EAD (p<0.001). At multivariate analysis, considering variables available at LT, MELD at LT>25 (OR=7.4) or 15‐25 (OR=3.2), graft macrovesicular steatosis≥30% (OR=6.7), HCV RNA positive at LT (OR=2.7), donor age>70 years (OR=2.0), earlier LT era (OR=1.8), cold ischemia time≥8 hours (OR=1.8) were significant risk factors for EAD. Conclusions. In HCV‐positive patients, MELD≥19 on day 5 post‐LT best predicts 90‐day graft loss. Preventing graft infection by pre/peri‐LT antiviral therapy reduces EAD incidence and could be most beneficial in high MELD patients and recipients of suboptimal grafts. 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 : Mercredi 19 avril 2017
    Ping‐Chun Li, Ashok Thorat, Long‐Bin Jeng, Horng‐Ren Yang, Ming‐Li Li, Chun‐Chieh Yeh, Te‐Hung Chen, Shih‐Chao Hsu, Kin‐Shing Poon
    Hepatic artery reconstruction in living donor liver transplantation using surgical loupes: Achieving low rate of hepatic arterial thrombosis in consecutive 741 recipients‐ Tips and tricks to overcome the poor hepatic arterial flow
    Background: The reconstruction of hepatic artery (HA) is most complex step in living donor liver transplantation (LDLT) due to smaller diameter of the artery and increased risk of HA related complications. Due to smaller diameter of the HA, many centres use microsurgical technique with interrupted sutures for arterial anastomosis. Aim of our study was to retrospectively investigate the outcomes after HA reconstruction performed under magnifying loupes using “parachute technique”. Materials and Methods: From August 2002 to 31st August 2016, LDLT was performed in 766 recipients. HA reconstruction for initial 25 LDLT surgeries was performed using microsurgery technique (Era I). From May 2007 till date, HA reconstruction was performed in 741 recipients by a “parachute technique” under surgical loupes (Era II). Results: HA reconstruction was performed using surgical loupes in 737 adults (Male:Female, 526:211) and 4 pediatric patients (Male:Female, 3:1). Average diameter of the donor graft HA was 2.8 mm (range,1 to 6.5 mm). The most notable factor in this era was quick HA anastomosis procedure with a mean time of 10 ± 5 minutes (range, 5‐30 minutes). In Era II, nine patients (1.21%) developed hepatic artery thrombosis (HAT) whereas 2 patients developed non‐thrombotic HA related complications. Extra‐anatomic HA reconstruction was performed in 14 patients due to either primary HA anastomosis failure or poor caliber recipient HA. Conclusions: Use of magnifying surgical loupes to perform HA reconstruction is safe, feasible, and yields low incidence of HA related complications. The “Parachute Technique” for HA reconstruction can achieve a speedy reconstruction without increasing risk of HAT. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Vendredi 07 avril 2017
    Jasmijn W. Selten, Cornelia J. Verhoeven, Veerle Heedfeld, Henk P. Roest, Jeroen de Jonge, Jacques Pirenne, Jos van Pelt, Jan. N.M. IJzermans, Diethard Monbaliu, Luc J.W. van der Laan
    The Release of MicroRNA‐122 During Liver Preservation is Associated with Early Allograft Dysfunction and Graft Survival After Transplantation
    Introduction: Early allograft dysfunction (EAD) after liver transplantation is associated with inferior graft survival. EAD is more prevalent in grafts from donation after circulatory death (DCD). However, accurate prediction of liver function remains difficult due to the lack of specific biomarkers. Recent experimental and clinical studies highlight the potential of hepatocyte‐derived microRNAs (miRNAs) as sensitive, stable and specific biomarkers of liver injury. The aim of this study was to determine whether miRNAs in graft preservation fluid are predictive for EAD after clinical liver transplantation and in an experimental DCD model. Methods: Graft preservation solutions of 83 liver grafts at the end of cold ischemia were analyzed for miRNAs by RT‐qPCR. Of these grafts 42% developed EAD after transplantation. Results were verified in pig livers (n=36) exposed to different lengths of warm ischemia time. Results: The absolute miR‐122 levels and miR‐122/miR‐222 ratios in preservation fluids were significantly higher in DCD grafts (p=0.001) and grafts developing EAD (p=0.004). In concordance, the miR‐122/miR‐222 ratios in perfusion fluid correlate with serum transaminase levels within the first 24 hours after transplantation. Long‐term graft survival was significantly diminished in grafts with high miR‐122/miR‐222 ratios (p=0.019). In the porcine DCD model, increased warm ischemia lead to higher absolute miR‐122 levels and relative miR‐122/miR‐222 ratios in graft perfusion fluid (p=0.009, and p=0.02, respectively). High miR‐122/miR‐222 ratios in pig livers were also associated with high AST levels after warm oxygenated reperfusion. Conclusion: Both absolute and relative miR‐122 levels in graft preservation solution are associated with DCD, EAD and early graft loss after liver transplantation. As shown in a porcine DCD model, miRNA release correlated with the length of warm ischemia times. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Vendredi 24 mars 2017
    Sara M. Lewin, Neil Mehta, R. Kate Kelley, John P. Roberts, Francis Y. Yao, Danielle Brandman
    Liver Transplant (LT) recipients with Nonalcoholic Steatohepatitis (NASH) Have Lower Risk Hepatocellular Carcinoma (HCC)
    Background: Liver transplantation is a well‐established treatment for HCC in carefully selected patients. Risk factors for tumors with poor prognostic features on explant have not been well described in a national cohort. Methods: We performed a retrospective cohort study of adult LT recipients with HCC transplanted from 4/8/12 (when explant pathology in UNOS became available) until 9/30/2014. We evaluated the association between listing diagnosis and other demographic factors with tumor features on explant using logistic regression. High‐risk tumor features included: >3 tumors, largest tumor >5 cm, presence of vascular invasion, presence of metastases, and poor differentiation of tumor. Results: 3733 LT recipients with HCC who had complete explant data in UNOS were included. The median age was 60, 78% were male and 68% were white. 2608 (70%) had hepatitis C (HCV), 271 (7%) had NASH, 246 (7%) had alcoholic cirrhosis, and 189 (5%) had hepatitis B (HBV) as the primary non‐HCC listing diagnosis. 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 post‐transplant (OR 5.00; p<0.001). Compared to 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 was not associated with high‐risk explant features. Conclusion: LT recipients with NASH‐associated HCC had fewer high‐risk tumor features on explant compared to 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 gender‐specific influences on tumor biology or due to selection criteria for transplant. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mardi 14 mars 2017
    Andrew P. Wright, Robert J. Fontana, Ryan W. Stidham
    Vedolizumab is Safe and Effective in Moderate to Severe Inflammatory Bowel Disease Following Liver Transplantation

    Date de mise en ligne : Mardi 14 mars 2017
    Tara A. Russell, Sarah Park, Vatche G. Agopian, Ali Zarrinpar, Douglas G. Farmer, Sean O'Neill, Islam Korayem, Samer Ebaid, Jeffrey Gornbein, Ronald W. Busuttil, Fady M. Kaldas
    Peri‐Transplant Pancreatitis: A Marker of High Mortality and Graft Failure in Liver Transplant Patients
    Perioperative pancreatitis is a significant comorbid condition in surgical patients, however the degree to which pancreatitis affects graft and overall survival in liver transplant recipients has not been evaluated. This study assesses the impact of pancreatitis on graft and patient survival in adult orthotopic liver transplantation (OLT). All patients undergoing OLT at a single academic institution from 2007‐2015 were reviewed. Pancreatitis was classified by method of diagnosis (intra‐operative or radiographic (IO/R) versus isolated serologic (IS)) and timing (pre‐operative versus post‐operative). Twenty‐three patients were identified with peri‐transplant pancreatitis (within 30 days pre‐ or post‐operatively). A control group of patients without pancreatitis undergoing OLT was composed of 775 patients. Graft failure/death rates for patients with versus without pancreatitis were 7.4% vs. 7.4% at 30 days, 33.3% vs. 12.6% at 90 days, and 44.4% vs. 26.9% at 12 months. Four patients with pancreatitis (17.4%) required emergent re‐transplantation, and subsequently died within 90 days of their second transplant. Overall, six patients with pancreatitis (26.1%) died within 90 days of transplantation. Patients with pancreatitis had a hazard ratio (HR) for death or graft failure of 2.28 as compared to controls (p<0.01). The effect of pancreatitis is most pronounced among those diagnosed by intra‐operative or radiographic findings, with an adjusted HR of 2.53 (p<0.01) and those diagnosed in the post‐operative period, adjusted HR 2.57 (p=0.01). Conclusion: Peri‐operative pancreatitis is associated with early graft failure and patient mortality, regardless of method or timing of diagnosis. Given these results, radiographic or intraoperative findings of pancreatitis should induce caution and potentially preclude OLT until resolved. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mardi 14 mars 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 Peri‐operative Use of Terlipressin in Adult Living Donor Liver Transplantation
    Background: Peri‐operative terlipressin (Tp) during living donor liver transplantation (LDLT) has been shown to reduce intra‐operative portal pressures and improve renal function. Its role and safety profile has never been evaluated in a double‐blinded RCT. Aim: To evaluate the haemodynamic effects, clinical benefits and safety of peri‐operative terlipressin infusion in adult LDLT. Methods: This was a single centre double‐blind RCT. Consenting adults with chronic liver disease and low risk of post‐transplant renal dysfunction (PTRD) undergoing their first LDLT were randomized. Study group (TpG) received an initial bolus of Tp during surgery followed by Tp infusion for 72 hours in post‐operative period. Placebo group (PbG) received saline infusion. Primary end point was portal pressure after arterial reperfusion. Multiple intra‐operative and postoperative variables served as secondary endpoints. Results: 41 patients were enrolled in the trial (TpG: 21, PbG:20). There were no significant differences in intra‐operative portal pressures, blood loss, fluid requirement, vasopressor requirement or urine output. Peak intra‐operative and end of surgery lactate levels were significantly higher in the Tp group. There was no difference in post‐operative liver function tests. Incidence of acute kidney injury as assessed by RIFLE criteria was lesser in Tp group (26.5% vs 60%, p=0.043). TpG had less post‐operative ascites, lesser need for percutaneous interventions and shorter hospital stay. Incidence of bradycardia requiring pharmacological intervention and withdrawal from study was significantly higher in Tp group. Conclusion: This study has not demonstrated reduction in post‐reperfusion portal pressure with Tp. However, Tp infusion reduced post‐operative ascitic drain output resulting in less frequent percutaneous interventions and reduced hospital stay. Intra‐operative hyperlactatemia and symptomatic bradycardia are major concerns. Its use should be restricted to patients with high volume ascites and needs close monitoring during drug infusion. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 27 fvrier 2017
    Jasmohan S. Bajaj, Andrew Fagan, Masoumeh Sikaroodi, Melanie B. White, Richard K. Sterling, HoChong Gilles, Douglas Heuman, R.T. Stravitz, Scott C. Matherly, Mohammed S. Siddiqui, Puneet Puri, Arun J. Sanyal, Velimir Luketic, Binu John, Michael Fuchs, Vishwadeep Ahluwalia, Patrick M. Gillevet
    Liver Transplant Modulates Gut Microbial Dysbiosis and Cognitive Function in Cirrhosis
    Liver transplant (LT) improves daily function and cognition in cirrhosis but a subset can remain impaired. Unfavorable microbiota or dysbiosis is observed in cirrhosis but the effect of LT on microbial composition; especially with poor post‐LT cognition, is unclear. Aims: (1) determine the effect of LT on gut microbiota and (b) to determine whether gut microbiota are associated with cognitive dysfunction post‐LT. We enrolled outpatient cirrhotics on the LT list and followed them till 6 months post‐LT. Cognition (Psychometric hepatic encephalopathy score, PHES), quality of life (HRQOL) and stool microbiota (multi‐tagged sequencing for diversity and taxa) was performed at both visits. Persistent cognitive impairment was defined as a stable/worsening PHES. Both pre/post‐LT data were compared with age‐matched healthy controls. We enrolled 45 patients (56±7 years, MELD 26±8). They received LT 6±3 months after enrollment and were re‐evaluated 7±2 months post‐LT with a stable course. A significantly improved HRQOL, PHES, with increase in microbial diversity, increase in autochthonous and decrease in potentially pathogenic taxa, were seen post‐LT compared to baseline. However, there was continued dysbiosis and HRQOL/cognitive impairment post‐LT compared to controls in 29% who did not improve PHES post‐LT. In these, Proteobacteria relative abundance was significantly higher and Firmicutes were lower post‐LT while the reverse occurred in the group that improved. Delta PHES was negatively correlated with delta Proteobacteria and positively with delta Firmicutes. Conclusions: LT improves gut microbiota diversity and dysbiosis compared to pre‐LT baseline but residual dysbiosis remains compared to controls. There is cognitive and HRQOL enhancement in general post‐LT but a higher Proteobacteria relative abundance change is associated with post‐transplant cognitive impairment. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 27 fvrier 2017
    A. Merdrignac, H. Jeddou, P. Houssel‐Debry, E. Flecher, M. Rayar, K. Boudjema
    Venous stent in liver transplant candidates: Dodging the top tip traps

    Date de mise en ligne : Mardi 21 fvrier 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 three months of life
    Background: Living donor liver transplantation is now an established technique for treating children with end‐stage liver disease. Few data exist about liver transplantation for exclusively young infants, especially infants of <3 months of age. We report our single‐center experience with 12 cases in which living donor liver transplantation (LT) 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. Patients and Methods: 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 reducing the left lateral segment in situ to mitigate the problem of graft to recipient size discrepancy. A reduced LLS graft was used in 11 cases and a segment 2 monosegment graft was used in one. 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. Results: There were significant differences in the PELD score and the conversion rate of tacrolimus to cyclosporine in younger infants. Furthermore, the incidence of biliary complications, blood stream infection, and CMV infection tended to be higher, while 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%. Conclusion: Living donor liver transplantation during the first three months of life appears to be a feasible option with excellent patient and graft survival. 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 : Mardi 10 janvier 2017
    Ping‐Chun Li, Ashok Thorat, Long‐Bin Jeng, Horng‐Ren Yang, Ming‐Li Li, Chun‐Chieh Yeh, Te‐Hung Chen, Shih‐Chao Hsu, Kin‐Shing Poon
    Successful Application Of Supra‐Coeliac Aorto‐Hepatic Conduit Using Saphenous Venous Graft In Right Lobe Living Donor Liver Transplantation

    Date de mise en ligne : Mardi 27 dcembre 2016
    Kyung‐Suk Suh, Hyo‐Sin Kim, Nam‐Joon Yi, Kwang‐Woong Lee, Suk Kyun Hong, Kyung Chul Yoon, Adianto Nugroho, Hyeyoung Kim
    Living donor liver transplantation using a right anterior section of the liver

    Date de mise en ligne : Jeudi 22 dcembre 2016
    B. Revilla‐Nuin, A. de Bejar, L. Martínez‐Alarcón, J.I. Herrero, C.M. Martínez‐Cáceres, P. Ramírez, A. Baroja‐Mazo, J.A. Pons
    Differential profile of activated regulatory T cell subsets and microRNAs in tolerant liver transplant recipients
    Regulatory T cells (Tregs) play a potential role in operational tolerance in liver transplant patients, and microRNAs (miRNAs) are known to be involved in immunological responses and tolerance. Thus, we analyzed the implication of different peripheral blood Treg subsets and miRNAs on liver transplantation tolerance in 24 tolerant (Tol) and 23 non‐tolerant (non‐Tol) liver transplant recipients by cellular, genetic and epigenetic approximation. Non‐Tol patients had a lower demethylation rate of the FOXP3 Treg‐specific demethylated region (TSDR) than Tol patients that correlated with the frequency of circulating Tregs. Tol patients presented a different signature of Treg subset markers compared with non‐Tol patients with increased expression of HELIOS and FOXP3 and a higher proportion of LAP+ Tregs and CD45RA‐HLA‐DR+ activated effector‐memory Tregs. The expression of miR95, miR24, miR31, miR146a and miR155 was higher in Tol than in non‐Tol patients and was positively correlated with activated Treg markers. Conclusions: These data suggest that activated effector‐memory Tregs and a TSDR‐demethylation state of Tregs may play a role in the complex system of regulation of liver transplantation tolerance. In addition, we describe a set of miRNAs differentially expressed in human liver transplant tolerant patients providing suggestive evidence that miRNAs are implied in the preservation of self‐tolerance as mediated by Tregs. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 01 avril 2015

    Date de mise en ligne : Vendredi 26 mai 2017
    Issue Information
    Issue Information

    Date de mise en ligne : Vendredi 26 mai 2017
    Thoetchai (Bee) Peeraphatdit, Patrick S. Kamath, Vijay H. Shah
    Beta‐blockers in patients with advanced cirrhosis: Red light, green light, yellow light…

    Date de mise en ligne : Vendredi 26 mai 2017
    Ghady Haidar, Nina Singh
    Improving the outcomes of human immunodeficiency virus/hepatitis C virus–coinfected transplant recipients: The answer is Blowin’ in the wind

    Date de mise en ligne : Vendredi 26 mai 2017
    Jennie Choe, David C. Mulligan
    Liver retransplantation: Recurrent primary sclerosing cholangitis may provide better outcomes

    Date de mise en ligne : Vendredi 26 mai 2017
    Sang Gyune Kim, Joseph J. Larson, Ji Sung Lee, Terry M. Therneau, W. Ray Kim
    Beneficial and harmful effects of nonselective beta blockade on acute kidney injury in liver transplant candidates
    Nonselective beta‐blockers (NSBBs) have played an important role in the prevention of portal hypertensive bleeding in patients with cirrhosis. However, recent studies have suggested that NSBBs may be harmful in some patients with end‐stage liver disease. The purpose of this article is to evaluate the association between use of NSBB and the incidence of acute kidney injury (AKI). We conducted a nested case‐control study in a cohort of liver transplant wait‐list registrants. Each patient with AKI was matched to a control by the Model for End‐Stage Liver Disease–Na score, age, serum creatinine, and follow‐up duration. Out of a total of 2361 wait‐list registrants, 205 patients developed AKI after a median follow‐up duration of 18.2 months. When compared with matched controls, ascites (79.0% versus 51.7%) and non‐Caucasian race (16.6% versus 7.8%) were more common among the cases. The frequency of NSBB use was higher among the cases than controls, albeit insignificantly (45.9% versus 37.1%; P = 0.08). In multivariate analyses, the impact of nonselective beta blockade on the development of AKI was dependent on the presence of ascites: nonselective beta blockade in patients with ascites significantly increased the risk of AKI (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.57‐6.95), whereas in patients without ascites, NSBB use reduced it (HR, 0.19; 95% CI, 0.06‐0.60). Potential benefits and harms of a NSBB in terms of AKI depend on the presence of ascites in liver transplant candidates. NSBB therapy in patients with cirrhosis may need to be individualized. Liver Transplantation 23 733–740 2017 AASLD.

    Date de mise en ligne : Vendredi 26 mai 2017
    Douglas R. Murken, Allison W. Peng, David D. Aufhauser, Peter L. Abt, David S. Goldberg, Matthew H. Levine
    Same policy, different impact: Center‐level effects of share 35 liver allocation
    Early studies of national data suggest that the Share 35 allocation policy increased liver transplants without compromising posttransplant outcomes. Changes in center‐specific volumes and practice patterns in response to the national policy change are not well characterized. Understanding center‐level responses to Share 35 is crucial for optimizing the policy and constructing effective future policy revisions. Data from the United Network for Organ Sharing were analyzed to compare center‐level volumes of allocation–Model for End‐Stage Liver Disease (aMELD) ≥ 35 transplants before and after policy implementation. There was significant center‐level variation in the number and proportion of aMELD ≥ 35 transplants performed from the pre– to post–Share 35 period; 8 centers accounted for 33.7% of the total national increase in aMELD ≥ 35 transplants performed in the 2.5‐year post–Share 35 period, whereas 25 centers accounted for 65.0% of the national increase. This trend correlated with increased listing at these centers of patients with Model for End‐Stage Liver Disease (MELD) ≥ 35 at the time of initial listing. These centers did not overrepresent the total national volume of liver transplants. Comparison of post–Share 35 aMELD to calculated time‐of‐transplant (TOT) laboratory MELD scores showed that only 69.6% of patients transplanted with aMELD ≥ 35 maintained a calculated laboratory MELD ≥ 35 at the TOT. In conclusion, Share 35 increased transplantation of aMELD ≥ 35 recipients on a national level, but the policy asymmetrically impacted practice patterns and volumes of a subset of centers. Longer‐term data are necessary to assess outcomes at centers with markedly increased volumes of high‐MELD transplants after Share 35. Liver Transplantation 23 741–750 2017 AASLD.

    Date de mise en ligne : Vendredi 26 mai 2017
    Sezai Yilmaz, Cuneyt Kayaalp, Burak Isik, Veysel Ersan, Emrah Otan, Sami Akbulut, Abuzer Dirican, Ramazan Kutlu, Aysegul Sagir Kahraman, Cengiz Ara, Mehmet Yilmaz, Bulent Unal, Cemalettin Aydin, Turgut Piskin, Dincer Ozgor, Mustafa Ates, Fatih Ozdemir, Volkan Ince, Cemalettin Koc, Adil Baskiran, Sait Murat Dogan, Bora Barut, Fatih Sumer, Serdar Karakas, Koray Kutluturk, Saim Yologlu, Harika Gozukara
    Reconstruction of Anomalous Portal Venous Branching in Right Lobe Living Donor Liver Transplantation: Malatya Approach
    Reconstruction of anomalous portal vein branching (APVB) during right lobe living donor liver transplantation (LDLT) can be challenging. The goal of this article is to describe our surgical technique, named the Malatya Approach, in case of APVB during right lobe LDLT. The technique unifies the APVB and obtains a funnel‐shaped common extension with a circumferential fence by a saphenous vein conduit. In total, 126 (10.6%) of 1192 right lobe grafts had APVB that were divided into 2 groups according to the adopted surgical techniques: the Malatya Approach group (n = 91) and the previously defined other techniques group (n = 35). Both groups were compared regarding portal vein thrombosis (PVT), postoperative 90‐day mortality and survival. PVT developed in 3 patients (3.3%) in the Malatya Approach group and developed in 10 (28.6%) patients for the other group (P < 0.001). There were 8 (8.8%) 90‐day mortalities in the Malatya Approach group (1 PVT related) and 15 patients (9 PVT related) died in the other techniques group (P < 0.001). Mean follow‐up time for both groups was similar (999.1 days for the Malatya Approach group versus 1024.7 days for the other group; P = 0.47), but longterm survival in the Malatya Approach group was better than in the other group (84.6% versus 40%; P < 0.001). Multivariate analysis revealed that the Malatya Approach group showed less PVT development and longer survival (P < 0.001). This technique is promising to avoid PVT and mortalities in cases of APVB during right lobe LDLT. Liver Transplantation 23 751–761 2017 AASLD.

    Date de mise en ligne : Vendredi 26 mai 2017
    Margaret V. Ragni, Abhinav Humar, Peter G. Stock, Emily A. Blumberg, Bijan Eghtesad, John J. Fung, Valentina Stosor, Nicholas Nissen, Michael T. Wong, Kenneth E. Sherman, Donald M. Stablein, Burc Barin
    Hemophilia Liver Transplantation Observational Study
    Hepatitis C virus (HCV) infection is the leading cause of liver disease in hemophilia patients. In those with human immunodeficiency virus (HIV)/HCV coinfection, the rate of liver disease progression is greater than in HCV monoinfected individuals. Despite antiretroviral therapy, which slows HCV liver disease progression, some require transplantation. Whether transplant outcomes are worse in hemophilic (H) rather than nonhemophilic (NH) candidates is unknown. In order to determine rates and predictors of pretransplant and posttransplant survival, we conducted a retrospective observational study using United Network for Organ Sharing national transplant registry data, comparing HCV+ H and NH candidates. We identified 2502 HCV+ liver transplant candidates from 8 US university‐based transplant centers, between January 1, 2004 to December 31, 2010, including 144 HIV+ (6%) and 2358 HIV–; 36 H (1%) and 2466 NH; 1213 (48%) transplanted and 1289 not transplanted. Other than male predominance and younger age, each were P < 0.001. Baseline data were comparable between H and NH. In univariate analysis, 90‐day pretransplant mortality was associated with higher baseline Model for End‐Stage Liver Disease (MELD; hazard ratio [HR] = 1.15; P < 0.001), lower baseline platelet count (HR = 0.9 per 25,000/µL; P = 0.04), and having HIV/HCV+ hemophilia (P = 0.003). In multivariate analysis, pretransplant mortality was associated with higher MELD (P < 0.001) and was significantly greater in HIV+ than HIV– groups (P = 0.001). However, it did not differ between HIV+ H and NH (HR = 1.7; P = 0.36). Among HIV/HCV+, posttransplant mortality was similar between H and NH, despite lower CD4 in H (P = 0.04). In conclusion, this observational study confirms that hemophilia per se does not have a specific influence on transplant outcomes and that HIV infection increases the risk of mortality in both H and NH patients. Liver Transplantation 23 762–768 2017 AASLD.

    Date de mise en ligne : Vendredi 26 mai 2017
    Jacqueline B. Henson, Yuval A. Patel, Lindsay Y. King, Jiayin Zheng, Shein‐Chung Chow, Andrew J. Muir
    Outcomes of liver retransplantation in patients with primary sclerosing cholangitis
    Liver retransplantation in patients with primary sclerosing cholangitis (PSC) has not been well studied. The aims of this study were to characterize patients with PSC listed for and undergoing retransplantation and to describe the outcomes in these patients. The United Network for Organ Sharing/Organ Procurement and Transplantation Network database was used to identify all primary liver transplantations and subsequent relistings and first retransplantations in adults with PSC between 1987 and 2015. A total of 5080 adults underwent primary transplantation for PSC during this period, and of the 1803 who experienced graft failure (GF), 762 were relisted, and 636 underwent retransplantation. Younger patients and patients with GF due to vascular thrombosis or biliary complications were more likely to be relisted, whereas those with Medicaid insurance or GF due to infection were less likely. Both 5‐year graft and patient survival after retransplantation were inferior to primary transplantation (P < 0.001). Five‐year survival after retransplantation for disease recurrence (REC), however, was similar to primary transplantation (graft survival, P = 0.45; patient survival, P = 0.09) and superior to other indications for retransplantation (graft and patient survival, P < 0.001). On multivariate analysis, mechanical ventilation, creatinine, bilirubin, albumin, advanced donor age, and a living donor were associated with poorer outcomes after retransplantation. In conclusion, although survival after liver retransplantation in patients with PSC was overall inferior to primary transplantation, outcomes after retransplantation for PSC REC were similar to primary transplantation at 5 years. Retransplantation may therefore represent a treatment option with the potential for excellent outcomes in patients with REC of PSC in the appropriate clinical circumstances. Liver Transplantation 23 769–780 2017 AASLD.

    Date de mise en ligne : Vendredi 26 mai 2017
    Woo‐Hyoung Kang, Shin Hwang, Gi‐Won Song, Young‐Joo Lee, Ki‐Hun Kim, Chul‐Soo Ahn, Deok‐Bog Moon, Dong‐Hwan Jung, Gil‐Chun Park, Sung‐Gyu Lee
    Prognostic effect of transarterial chemoembolization–induced complete pathological response in patients undergoing liver resection and transplantation for hepatocellular carcinoma
    Transarterial chemoembolization (TACE)–induced complete pathological response (CPR) is known to improve postresection outcomes of hepatocellular carcinoma (HCC). We aimed to assess the prognostic effects of CPR after preoperative TACE for HCC in patients who underwent hepatic resection (HR) or liver transplantation (LT). The clinical outcomes of patients showing CPR after HR (n = 110) or LT (n = 233) were analyzed. The control groups comprised patients with minimal recurrence risk as naïve single HCC ≤ 2 cm for HR (n = 476), and 1 or 2 HCCs ≤ 2 cm for LT (n = 184). Among HR study patients, 1‐, 3‐, and 5‐year tumor recurrence rates were 18.5%, 50.6%, and 58.7% respectively, which were higher than those of controls (P < 0.001). The 1‐, 3‐, and 5‐year patient survival rates were 97.8%, 82.0%, and 69.1%, respectively, which were lower than those of controls (P < 0.001). Among LT study patients, 1‐, 3‐, and 5‐year tumor recurrence rates were 4.1%, 7.9%, and 7.9%, respectively, which were higher than those of controls (P = 0.019). The 1‐, 3‐, and 5‐year patient survival rates were 92.7%, 89.2%, and 86.9%, respectively, which were not different than those of controls (P = 0.11). LT recipients had lower recurrence and higher survival rates compared with HR patients (P < 0.001). The tumor recurrence site was mainly intrahepatic in HR patients. There was no difference between the incidences of extrahepatic recurrence in the HR study group and all‐site recurrence in the LT study group (P = 0.61). We concluded that the prognostic effect of TACE‐induced CPR for HCC patients appears to be limited to downstaging. LT recipients benefited more from CPR than HR patients. Liver Transplantation 23 781–790 2017 AASLD.

    Date de mise en ligne : Vendredi 26 mai 2017
    Hiroaki Haga, Irene K. Yan, David A. Borrelli, Akiko Matsuda, Mansi Parasramka, Neha Shukla, David D. Lee, Tushar Patel
    Extracellular vesicles from bone marrow–derived mesenchymal stem cells protect against murine hepatic ischemia/reperfusion injury
    Hepatic ischemia/reperfusion injury (IRI) and associated inflammation contributes to liver dysfunction and complications after liver surgery and transplantation. Mesenchymal stem cells (MSCs) have been reported to reduce hepatic IRI because of their reparative immunomodulatory effects in injured tissues. Recent studies have highlighted beneficial effects of extracellular vesicles from mesenchymal stem cells (MSC‐EV) on tissue injury. The effects of systemically administered mouse bone marrow–derived MSC‐EV were evaluated in an experimental murine model of hepatic IRI induced by cross‐clamping the hepatic artery and portal vein for 90 minutes followed by reperfusion for periods of up to 6 hours. Compared with controls, intravenous administration of MSC‐EV 30 minutes prior to IRI dramatically reduced the extent of tissue necrosis, decreased caspase 3–positive and apoptotic cells, and reduced serum aminotransferase levels. MSC‐EV increased hepatic messenger RNA (mRNA) expression of NACHT, LRR, and PYD domains‐containing protein 12, and the chemokine (C‐X‐C motif) ligand 1, and reduced mRNA expression of several inflammatory cytokines such as interleukin 6 during IRI. MSC‐EV increased cell viability and suppressed both oxidative injury and nuclear factor kappa B activity in murine hepatocytes in vitro. In conclusion, the administration of extracellular vesicles derived from bone marrow–derived MSCs may ameliorate hepatic IRI by reducing hepatic injury through modulation of the inflammatory response.Liver Transplantation 23 791–803 2017 AASLD.

    Date de mise en ligne : Vendredi 26 mai 2017
    Ding Cao, Menghao Wang, Junhua Gong, Sidong Wei, Jianping Gong, Jinzheng Li
    Exogenous vascular endothelial growth factor delivery prior to endothelial precursor cell transplantation in orthotopic liver transplantation–induced hepatic ischemia/reperfusion injury
    Vascular endothelial growth factor (VEGF) promotes angiogenesis in vivo. We hypothesized that exogenous delivery of VEGF prior to bone marrow–derived endothelial precursor cell (EPC) transplantation may improve orthotopic liver transplantation (OLT)–induced hepatic ischemia/reperfusion injury (HIRI). OLT between Sprague Dawley donor rats and inbred LEW Wistar recipient rats was performed in 6 experimental groups to comparatively assess the effects of the VEGF gene: an untreated normal control group, a surgical control group, a liposomal control group, a VEGF group receiving only the liposome‐encapsulated VEGF plasmid, an EPC group receiving only EPCs, and an EPC+VEGF group receiving the liposome‐encapsulated VEGF plasmid followed by EPCs. VEGF plasmid delivery to liver tissue, endogenous VEGF, and vascular endothelial growth factor receptor (VEGFR) expression, liver transaminase levels, hepatocellular injury levels, apoptosis, apoptotic biomarkers, hepatotrophic mitogens, angiogenesis, and nitric oxide synthase (NOS) activity were assayed after OLT. Exogenous VEGF gene delivery prior to EPC transplantation significantly increased endogenous VEGF and VEGFR expression, significantly reduced liver transaminase levels, significantly reduced hepatocellular injury levels, significantly reduced hepatic apoptosis levels, and significantly reduced several apoptotic biomarkers (ie, B cell lymphoma 2–associated X protein/B cell lymphoma 2 ratio, caspase 3 activity, and heat shock protein 70 expression) in post‐OLT–induced HIRI. Moreover, VEGF gene delivery prior to EPC transplantation significantly increased hepatotrophic mitogen expression (ie, epidermal growth factor, heparin‐binding epidermal growth factor–like growth factor, hepatocyte growth factor, and transforming growth factor α), angiogenesis, and NOS activity in post‐OLT–induced HIRI. In conclusion, exogenous liposomal delivery of the VEGF gene prior to bone marrow–derived EPC transplantation may be an effective strategy in decreasing OLT‐induced HIRI. Liver Transplantation 23 804–812 2017 AASLD.

    Date de mise en ligne : Vendredi 26 mai 2017
    Qiang Zhu, Changyong Li, Kunpeng Wang, Shi Yue, Longfeng Jiang, Michael Ke, Ronald W. Busuttil, Jerzy W. Kupiec‐Weglinski, Feng Zhang, Ling Lu, Bibo Ke
    Phosphatase and tensin homolog–β‐catenin signaling modulates regulatory T cells and inflammatory responses in mouse liver ischemia/reperfusion injury
    The phosphatase and tensin homolog (PTEN) deleted on chromosome 10 plays an important role in regulating T cell activation during inflammatory response. Activation of β‐catenin is crucial for maintaining immune homeostasis. This study investigates the functional roles and molecular mechanisms by which PTEN–β‐catenin signaling promotes regulatory T cell (Treg) induction in a mouse model of liver ischemia/reperfusion injury (IRI). We found that mice with myeloid‐specific phosphatase and tensin homolog knockout (PTENM‐KO) exhibited reduced liver damage as evidenced by decreased levels of serum alanine aminotransferase, intrahepatic macrophage trafficking, and proinflammatory mediators compared with the PTEN‐proficient (floxed phosphatase and tensin homolog [PTENFL/FL]) controls. Disruption of myeloid PTEN‐activated b‐catenin promoted peroxisome proliferator‐activated receptor gamma (PPARγ)‐mediated Jagged‐1/Notch signaling and induced forkhead box P3 (FOXP3)1 Tregs while inhibiting T helper 17 cells. However, blocking of Notch signaling by inhibiting γ‐secretase reversed myeloid PTEN deficiency‐mediated protection in ischemia/reperfusion–triggered liver inflammation with reduced FOXP3+ and increased retinoid A receptor–related orphan receptor gamma t–mediated interleukin 17A expression in ischemic livers. Moreover, knockdown of β‐catenin or PPARγ in PTEN‐deficient macrophages inhibited Jagged‐1/Notch activation and reduced FOXP3+ Treg induction, leading to increased proinflammatory mediators in macrophage/T cell cocultures. In conclusion, our findings demonstrate that PTEN–β‐catenin signaling is a novel regulator involved in modulating Treg development and provides a potential therapeutic target in liver IRI. Liver Transplantation 23 813–825 2017 AASLD.

    Date de mise en ligne : Vendredi 26 mai 2017
    Hongqun Liu, Saumya Jayakumar, Mouhieddin Traboulsi, Samuel S. Lee
    Cirrhotic cardiomyopathy: Implications for liver transplantation
    The majority of patients on a waiting list for liver transplantation have end‐stage liver disease. Because of the marked peripheral vasodilatation of end‐stage cirrhosis that masks a latent myocardial dysfunction, cardiac abnormalities in the resting state are usually subclinical and escape the attention of physicians. However, when challenged, the systolic and diastolic contractile responses are attenuated. In addition to these contractile abnormalities, morphological changes, such as enlargement or hypertrophy of cardiac chambers, and electrophysiological repolarization changes, including a prolonged QT interval, can be observed. The constellation of these cardiac abnormalities is termed cirrhotic cardiomyopathy. Liver transplantation induces significant cardiovascular stress. Clamping of the inferior vena cava and portal vein, hemorrhage and blood/volume infusion, and ischemia/reperfusion all cause hemodynamic fluctuation. The changing cardiac preload and afterload status increases the cardiac workload, and thus, the previously subclinical ventricular dysfunction may manifest as overt heart failure during the operative and perioperative periods. Cardiac dysfunction contributes to morbidity and mortality associated with liver transplantation. Cardiovascular events are the third leading cause of death in liver recipients. However, because liver transplantation is the only definitive treatment for end‐stage liver failure and also appears to reverse cardiac abnormalities, it is important to understand the challenges of the heart in liver transplantation. This review focuses on cardiac status before, during, and after liver transplantation. Liver Transplantation 23 826–835 2017 AASLD.

    Date de mise en ligne : Vendredi 26 mai 2017
    Benjamin Menahem, Jean Lubrano, Christophe Duvoux, Andrea Mulliri, Arnaud Alves, Charlotte Costentin, Ariane Mallat, Guy Launoy, Alexis Laurent
    Liver transplantation versus liver resection for hepatocellular carcinoma in intention to treat: An attempt to perform an ideal meta‐analysis
    This meta‐analysis compared the effects of liver transplantation (LT) and liver resection (LR) on overall survival (OS) and disease‐free survival (DFS) in patients with hepatocellular carcinoma (HCC) small transplantable HCC or within Milan criteria. Articles comparing LR with LT for HCC, based on Milan criteria or small size, published up to June 2015 were selected, and a meta‐analysis was performed. No randomized controlled trial has been published to date comparing survival outcomes in patients with HCC who underwent LR and LT. Nine studies were identified, including 570 patients who underwent LR and 861 who underwent LT. For HCC within the Milan criteria, the 1‐year OS rates following LR and LT were 84.5% (473/560) and 84.4% (710/841), respectively (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.71‐1.33; P = 0.8), and the 5‐year OS rates were 47.9% (273/570) and 59.3% (509/858), respectively (OR, 0.60; 95% CI, 0.35‐1.02; P = 0.06). One‐year DFS rates were similar (OR, 1.00; 95% CI, 0.39‐2.61; P = 1.00), whereas the 3‐year DFS rate was significantly lower in the LR group (54.4%, 210/386) than in the LT group (74.2%, 317/427; OR, 0.24; 95% CI, 0.07‐0.80; P = 0.02), and the 5‐year DFS rate was significantly lower for LR than LT (OR, 0.18; 95% CI, 0.06‐0.53; P < 0.01). For small HCCs, the 5‐year OS rate was significantly lower for patients who underwent LR than LT (OR, 0.30; 95% CI, 0.19‐0.48; P < 0.001). In conclusion, relative to LR, LT in patients with HCC meeting the Milan criteria had no benefits before 10 years for OS. For DFS, the benefit is obtained after 3 years. Liver Transplantation 23 836–844 2017 AASLD.

    Date de mise en ligne : Vendredi 26 mai 2017
    Jin‐Young Huh, Danbi Lee, Jihyun Ahn, Ju Hyun Shim, Young‐Suk Lim, Gil‐Chun Park, Gi‐Won Song, Ki‐Hun Kim, Dong‐Hwan Jung, Deok‐Bog Moon, Shin Hwang, Sung Gyu Lee, Sei Won Lee, Jin‐Woo Song, Yeon‐Mok Oh, Tae Sun Shim, Kyung‐Wook Jo
    Impact of emergency adult living donor liver transplantation on the survival of patients with antituberculosis therapy‐induced acute liver failure

    Date de mise en ligne : Vendredi 26 mai 2017
    Suk Kyun Hong, Kwang‐Woong Lee, Hyo‐Sin Kim, Kyung Chul Yoon, Sung‐Woo Ahn, Jin Yong Choi, Hyeyoung Kim, Nam‐Joon Yi, Kyung‐Suk Suh
    Optimal bile duct division using real‐time indocyanine green near‐infrared fluorescence cholangiography during laparoscopic donor hepatectomy

    Date de mise en ligne : Vendredi 05 mai 2017
    Kojiro Taura, Toshimi Kaido, Takayuki Anazawa, Shintaro Yagi, Hideaki Okajima, Shinji Uemoto
    Living donor liver transplantation with a left trisegmental graft from a donor with anomalous branching of the portal vein

    Date de mise en ligne : Vendredi 26 mai 2017
    Paolo Magistri, Giuseppe Tarantino, Roberto Ballarin, Andrea Coratti, Fabrizio Di Benedetto
    Robotic liver donor right hepatectomy: A pure, minimally invasive approach

    Date de mise en ligne : Mercredi 10 mai 2017
    Po‐Da Chen, Yao‐Ming Wu

    Date de mise en ligne : Vendredi 26 mai 2017
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