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Les derniers abstracts de la revue Liver Transplantation :

    Date de mise en ligne : Lundi 27 fvrier 2017
    Amy Tan, Sander S. Florman, Thomas D. Schiano
    Genetic, Hematological and Immunological Disorders Transmissible with Liver Transplantation
    It is well recognized that solid organ transplantation can transmit bacterial infection, chronic viral hepatitis as well as certain cancers. As indications for liver transplantation have expanded, it has been used to treat and even cure certain genetic cholestatic disorders, urea cycle defects and coagulation abnormalities; many of these conditions are potentially transmissible with liver transplantation as well. It is important for clinicians and transplant patients to be aware of these potentially transmissible conditions as unexplained post‐liver transplant complications can sometimes be related to donor transmission of disease and thus should prompt a thorough exploration of the donor allograft history. Herein, we will review the reported genetic, metabolic, hematologic, and immunological disorders that are transmissible with liver transplantation and describe clinical scenarios in which these cases have occurred, such as in inadvertent or recognized transplantation of a diseased organ, domino transplantation, and with living related liver donation. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 27 fvrier 2017
    Hazel Marecki, Adel Bozorgzadeh, Robert Porte, Henri Leuvenink, Korkut Uygun, Paulo Martins
    Liver ex‐vivo machine perfusion preservation: A review of the methodology and results of large animal studies and clinical trials
    Ex‐vivo machine perfusion is a promising way to better preserve livers prior to transplantation. Currently, no methodology has verified benefit over simple cold storage. Before becoming clinically feasible, machine perfusion requires validation in models that reliably predict human performance. Such a model has been found in porcine liver, who's physiological, anatomical, and immunological characteristics closely resemble the human liver. Since the 1930s, researchers have explored machine perfusion as preservation, but only recently have clinical trials been performed. Making this technology clinically available holds the promise of expanding the donor pool through more effective preservation of extended criteria donor livers. Machine perfusion promises to decrease delayed graft function, primary non‐function and biliary strictures, all common failure modes of transplanted extended criteria donor livers. While hypothermic machine perfusion has become the standard for kidney ex‐vivo preservation, the precise settings and clinical role for liver machine perfusion has not yet been established. In research, there are two schools of thought: normothermic machine perfusion, closely mimicking physiologic conditions, and hypothermic machine perfusion, to maximize preservation. Here, we review the literature for porcine ex‐vivo machine perfusion, with aim to summarize perfusion settings and outcomes pertinent to the clinical establishment of machine perfusion. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 27 fvrier 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
    BACKGROUND: Reconstruction of anomalous portal venous branching (APVB) during right lobe living donor liver transplantation (LDLT) can be challenging. OBJECTIVE: To describe our surgical technique, named the Malatya Approach, in case of APVP during right lobe LDLT. The technique includes the unification of the APVB and to obtain a funnel shaped common extension with a circumferential fence by a saphenous vein conduit. METHODS: Total 126 (10.6%) of 1192 right lobe grafts had APVB that were divided into two 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. RESULTS: PVT developed in three cases (3.3%) in the Malatya Approach group, and developed in ten cases (28.6%) for the other group (p<0.001). There were eight (8.8%) 90‐day mortalities in the Malatya Approach group (one PVT related) and 15 patients (nine PVT related) died in the other techniques group (p<0.001). Mean follow‐up time for both groups were similar (999,09 days for the Malatya Approach group vs 1024,69 days for other group, p=0.47), but long term survival in the Malatya Approach group was better than in the other group (84.6% vs. 40%, p<0.001). Multivariate analysis revealed that the Malatya Approach group showed less PVT development and longer survival (p<0.001). CONCLUSIONS: This technique is promising to avoid PVT and mortalities in cases of APVB during right lobe LDLT. 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
    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 TACE‐induced complete pathological response in patients undergone liver resection and transplantation for hepatocellular carcinoma
    Transcatheter arterial chemoembolization (TACE)‐induced complete pathological response (CPR) is known to improve post‐resection 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 one or two 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 to HR patients (p<0.001). Tumor recurrence site was mainly intrahepatic in HR patients. There was no difference between the incidences of extrahepatic recurrence in HR study group and all‐site recurrence in 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 are benefited more from CPR than HR patients. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 27 fvrier 2017
    David S. Goldberg, Matthew Levine, Seth Karp, Richard Gilroy, Peter L. Abt
    Share 35 Changes Center Level Liver Acceptance Practices
    Share 35 was implemented to provide improved access to organs for patients with MELD scores ≥35. However, little is known about the impact of Share 35 on organ offer acceptance rates. We evaluated all liver offers to adult patients that were ultimately transplanted between 1/1/2011‐12/31/2015. The analyses focused on patients ranked in the top five positions of a given match run, and used multi‐level mixed‐effects models, clustering on individual waitlist candidate and transplant center. There was a significant interaction between Share 35 era and MELD category (p<0.001). Comparing offers to MELD score ≥35 patients, offers post‐Share 35 were 36% less likely to be accepted compared to offers to MELD score ≥35 patients pre‐Share 35 (adjusted OR: 0.64). There was no clinically meaningful difference in the DRI of livers that were declined for patients with an allocation MELD score ≥35 in the pre‐ vs post‐Share 35 era. Organ offer acceptance rates for patients with an allocation MELD≥35 decreased in every region post‐Share 35; the magnitude of these changes was bigger in regions 2, 3, 4, 5, 6, 7, and 11, compared to regions 8 and 9 that had regional sharing in place pre‐Share 35. There were significant changes in organ offer acceptance rates at the center level pre‐ vs post‐Share 35, and these changes varied across centers (p<0.001). Conclusions: In liver transplant candidates achieving a MELD score ≥35, liver acceptance of offers declined significantly after implementation of Share 35. The alterations in behavior at the center level suggest that practice patterns changed as a direct result of Share 35. Changes in organ acceptance under even broader organ sharing (redistricting) would likely be even greater, posing major logistical and operational challenges, while potentially increasing discard rates, thus decreasing the total number of transplant nationally. 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 : Lundi 27 fvrier 2017
    Elizabeth J. Carey, Jennifer C. Lai, Connie W. Wang, Srinivasan Dasarathy, Iryna Lobach, Aldo J. Montano‐Loza, Michael A. Dunn
    A multi‐center study to define sarcopenia in patients with end‐stage liver disease
    Sarcopenia is associated with increased waitlist mortality, but a standard definition is lacking. In this retrospective study, we sought to determine the optimal definition of sarcopenia in end‐stage liver disease (ESLD) patients awaiting LT. Included were 396 patients newly listed for LT in 2012 at five North American transplant centers. All CT scans were read by two individuals with inter‐observer correlation of 98%. Using image analysis software, the total cross‐sectional area (cm2) of abdominal skeletal muscle at L3 was measured. The skeletal muscle index (SMI), which normalizes muscle area to patient height, was then calculated. The primary outcome was waitlist mortality, defined as death on the waitlist or removal from the waitlist for reasons of clinical deterioration. Sex‐specific potential cut‐off values to define sarcopenia were determined with a grid search guided by log‐rank test statistics. Optimal search method identified potential cutoffs to detect survival differences between groups. The overall median SMI was 47.6 cm2/m2: 50.0 in men and 42.0 in women. At a median of 8.8 months follow‐up, mortality was 25% in men and 36% in women. Patients who died had lower SMI than those who survived (45.6 vs 48.5 cm2/m2, p<0.001) and SMI was associated with waitlist mortality (HR 0.95, p<0.001). Optimal search method yielded SMI cut‐offs of 50 cm2/m2 for men and 39 cm2/m2 for women; these cutoff values best combined statistical significance with a sufficient number of events to detect survival differences between groups. In conclusion, we recommend that an SMI < 50 cm2/m2 for men and < 39 cm2/m2 for women be used to define sarcopenia in patients with ESLD awaiting LT. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Samedi 25 fvrier 2017
    Francesco Esposito, Chetana Lim, Chady Salloum, Michael Osseis, Laurence Baranes, Aurelien Amiot, Philippe Compagnon, Daniel Azoulay
    Intra‐gastric migration of a mesenterico‐portal polytetrafluoroethylene (PTFE) jump graft after liver transplantation

    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 : Lundi 13 fvrier 2017
    Andrew P. Keaveny, C. Burcin Taner
    Prioritization for Liver Transplantation: Reconsidering Survival Benefit

    Date de mise en ligne : Samedi 11 fvrier 2017
    Fernando Agüero, Alejandro Forner, Andrés Valdivieso, Marino Blanes, Rafael Barcena, Christian Manzardo, Antoni Rafecas, Lluis Castells, Manuel Abradelo, Pilar Barrera‐Baena, Luisa González‐Diéguez, Magdalena Salcedo, Trinidad Serrano, Miguel Jiménez‐Pérez, José Ignacio Herrero, Mikel Gastaca, Victoria Aguilera, Juan Fabregat, Santos del Campo, Itxarone Bilbao, Carlos Jiménez Romero, Asunción Moreno, Antoni Rimola, José M. Miro,
    HIV‐infected Liver Transplant Recipients with Incidental Hepatocellular Carcinoma: A Prospective Multicenter Nationwide Cohort Study
    There is a lack of data on incidental hepatocellular carcinoma (iHCC) in the setting of liver transplantation (LT) in HIV infected patients. This study aims to describe the frequency, histopathological characteristics and outcomes of HIV‐infected LT recipients with iHCC from a Spanish, multicenter cohort in comparison with a matched cohort of LT patients without HIV infection. Fifteen (6%) out of 271 patients with HIV infection who received LT in Spain from 2002‐2012 and 38 (5%) out of the 811 HIV‐uninfected counterparts presented iHCC in liver explants (p=0.58). Patients with iHCC constitute the present study population. All patients also had HCV‐related cirrhosis. There were no significant differences in histopathological features of iHCC between the two groups. Most patients showed a small number and size of tumoral nodules, and few patients had satellite nodules, microvascular invasion or poorly differentiated tumors. After a median follow‐up of 49 months, no patient developed HCC recurrence post‐LT. HIV‐infected LT recipients tended to have lower survival than their HIV‐uninfected counterparts at one (73% vs. 92%), three (67% vs. 84%) and five years (50% vs. 80%) (p=0.06). There was also a trend to a higher frequency of HCV recurrence as a cause of death in the former (33% vs. 10%; p=0.097). In conclusion: Among LT recipients for HCV‐related cirrhosis, the incidence and histopathological features of iHCC in HIV‐infected and HIV‐uninfected patients were similar. No patient developed HCC recurrence. However, post‐LT survival was lower in HIV‐infected patients probably because of a more aggressive HCV recurrence. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Vendredi 10 fvrier 2017
    Ding Cao, Menghao Wang, Junhua Gong, Sidong Wei, Jianping Gong, Jinzheng Li
    Exogenous VEGF Delivery Prior to Endothelial Precursor Cell Transplantation in Orthotopic Liver Transplant‐Induced Hepatic Ischemia Reperfusion Injury
    Background: 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). Methods: OLT between Sprague Dawley donor rats and inbred LEW Wistar recipient rats was performed in six experimental groups to comparatively assess the effects of 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 VEGF receptor (VEGFR) expression, liver transaminase levels, hepatocellular injury levels, apoptosis, apoptotic biomarkers, hepatotrophic mitogens, angiogenesis, and nitric oxide synthase (NOS) activity were assayed post‐OLT. Results: 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 (i.e., Bax/Bcl‐2 ratio, caspase‐3 activity, and Hsp70 expression) in post‐OLT‐induced HIRI. Moreover, VEGF gene delivery prior to EPC transplantation significantly increased hepatotrophic mitogen expression (i.e., EGF, HB‐EGF, HGF, and TGF‐α), angiogenesis, and NOS activity in post‐OLT‐induced HIRI. Conclusions: Exogenous liposomal delivery of the VEGF gene prior to bone marrow‐derived EPC transplantation may be an effective strategy in decreasing OLT‐induced HIRI. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Vendredi 10 fvrier 2017
    Elena Fernandez‐Sevilla, Marc‐Antoine Allard, Jasmijn Selten, Nicolas Golse, Eric Vibert, Antonio Sa Cunha, Daniel Cherqui, Denis Castaing, René Adam
    Recurrence of hepatocellular carcinoma after liver transplantation: Is there a place for resection?
    Introduction: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is widely considered as a terminal condition. Therefore, the role of surgery is uncertain in this case. The purpose of this study was to identify the prognostic factors of survival after post‐LT HCC recurrence and evaluate the impact of surgery in this setting. Patients and Methods: All patients transplanted for HCC between 1991 and 2013 in a single institution and who further developed a post‐LT recurrence were included in this study. Univariate and multivariate analyses were performed to identify factors affecting post‐recurrence survival. Results: Of the 493 patients transplanted for HCC, a total of 70 (14.2%) consecutive patients developed a recurrence after a median disease‐free interval of 17 months. Median survival from the time of recurrence was 19 months, with a 3‐year post‐recurrence survival of 26%. Most recurrences were extrahepatic (lung, lymph node and bone) (n=51; 72.9%), whereas only intrahepatic recurrences were observed in 2 patients (2.8%). Both intrahepatic and extrahepatic locations were found in 17 patients (24.3%). A total of 22 patients (31.4%) underwent macroscopically complete resection of the recurrence (intrahepatic, n=2 and extrahepatic, n=20). The median survival for resected patients after transplantation was 35 months compared to 15 months for non‐resected patients (P <0.001). In multivariate analysis, the independent unfavorable factors of post‐recurrence survival were AFP level > 100 ng/ml at relapse (HR 2.09 [1.07‐4.06], P =0.03), intrahepatic location (HR 1.80 [1.01‐3.21], P =0.048), and multifocal recurrence (HR 1.79 [1.02‐3.11], P =0.04). The management including surgery (HR 0.36 [0.18‐0.73], P =0.004) was identified as an independent favorable factor. Conclusions: Recurrence of HCC after liver transplantation is associated with a poor prognosis. However, resection is associated with improved survival and should, therefore, be considered when feasible. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Vendredi 10 fvrier 2017
    Sang Gyune Kim, Joseph J. Larson, Ji Sung Lee, Therneau M. Terry, W. Ray Kim
    Beneficial and Harmful Effects of Non‐selective Beta Blockade on Acute Kidney Injury in Liver Transplant Candidates
    Non‐selective beta‐blockers have played an important role in the prevention of portal hypertensive bleeding in cirrhotic patients. However, recent studies have suggested that non‐selective beta‐blockers may be harmful in some patients with end‐stage liver disease. To evaluate the association between use of non‐selective beta‐blocker and the incidence of acute kidney injury (AKI). We conducted a nested case‐control study in a cohort of liver transplant waitlist registrants. Each patient with AKI was matched to a control by the model for end‐stage liver disease (MELD)‐Na score, age, serum creatinine, and follow‐up duration. Out of a total of 2,361 waitlist registrants, 205 patients developed AKI after a median follow‐up duration of 18.2 months. When compared to 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 non‐selective beta‐blocker use was higher among the cases than controls, albeit insignificantly (45.9% versus 37.1%, P = .08). In multivariable analyses, the impact of non‐selective beta‐blockade on the development of AKI was dependent upon the presence of ascites: non‐selective 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), while in patients without ascites, non‐selective beta‐blocker use reduced it (HR, 0.19; 95% CI, 0.06‐0.60). Potential benefits and harms of a non‐selective beta‐blocker in terms of AKI depend on the presence of ascites in liver transplant candidates. Non‐selective beta‐blocker therapy in cirrhotic patients may need to be individualized. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 08 fvrier 2017
    Cybele Lara R. Abad, Brian D. Lahr, Raymund R. Razonable
    Epidemiology and Risk Factors for Infection after Living Donor Liver Transplantation
    BACKGROUND: The epidemiology of infections after living donor liver transplantation is limited. We aimed to study the epidemiology and risk factors of infections after living donor liver transplantation. METHODS: The medical records of 223 adult patients who underwent living donor liver transplantation from January 1, 2000 – August 31, 2015 were reviewed for all infections occurring up to 1 year. We estimated the cumulative incidence of infection using the Kaplan Meier product limit method. Risk factors were analyzed with time‐dependent Cox regression modeling. RESULTS: The majority of patients were Caucasian (95%) and male (65%), and the median age at transplantation was 55 years. The most common indication for transplantation was primary sclerosing cholangitis (38%). A total of 122 patients developed an infection during the follow‐up period (1 year cumulative event rate of 56%), with the majority (66%) of these occurring within 30 days after transplantation. Enterococcus sp. was the most frequent pathogen identified. Multivariable analysis showed that increased MELD score (per 10‐point change: HR=1.59), history of recurrent infections prior transplant (HR=2.01), Roux‐en‐Y anastomosis (HR=2.37), increased log‐number of packed RBC transfusions (HR=1.39), and biliary complications (HR=4.26) were independently associated with a higher risk of infection. CONCLUSIONS: Infections occur commonly after living donor liver transplantation, with most infections occurring early and related to the hepatobiliary system. Higher MELD scores, the type of biliary anastomosis, presence of biliary complications, and prior pre‐transplant infections are independently associated with a higher risk of infections. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 06 fvrier 2017
    Stephen J. Wigmore, Gabriel C. Oniscu
    Side‐stream dark field videomicroscopy for evaluating liver microcirculation in vivo

    Date de mise en ligne : Samedi 04 fvrier 2017
    Ryutaro Hirose, Julie Heimbach
    Defining disparities in liver transplantation: The devil is in the details

    Date de mise en ligne : Vendredi 03 fvrier 2017
    D D'Avola, V Cuervas‐Mons, J Martí, J Ortiz de Urbina, L Lladó, C Jimenez, E Otero, F Suarez, JM Rodrigo, MA Gómez, E Fraga, P Lopez, T Serrano, A Rios, E Fábrega, JI Herrero
    Cardiovascular morbidity and mortality after liver transplantation: The protective role of Mycophenolate Mofetil
    Cardiovascular (CV) diseases are recognized long‐term causes of death after liver transplantation (LT). The objective of this multicenter study was to analyse the prevalence and the evolution of CV risk factors and CV morbidity and mortality in 1819 liver transplant recipients along 5 years after LT. The influence of baseline variables on survival, morbidity and mortality was studied. There was a continuous and significant increase of the prevalence of all the CV risk factors (except smoking) after LT. CV diseases were the fourth cause of mortality in the 5 years after LT, causing 12% of deaths during the follow‐up. Most CV events (39%) occurred in the first year after LT. Pre‐existing CV risk factors such as age, pre‐LT CV events, diabetes, metabolic syndrome and hyperuricemia, and mycophenolate‐free immunosuppressive therapy, increased post‐LT CV morbidity and mortality. The development of new onset CV risk factors after LT, such as dyslipidemia and obesity, independently affected late CV morbidity and mortality. Tacrolimus and steroids increased the risk of post‐transplant diabetes, while cyclosporine increased the risk of arterial hypertension dyslipidemia and metabolic syndrome. Conclusion: cardiovascular complications and CV mortality are frequent in LT recipients. Pre‐existing CV risk factors, immunosuppressive drugs but also the early new onset of obesity and dyslipidemia after LT play an important role on late CV complications. A strict metabolic control in the immediate post‐LT is advisable for improving CV risk of LT recipients. 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 : Jeudi 02 fvrier 2017
    A Rammohan, S Govil, J Vargese, V Kota, MS Reddy, M Rela
    Changing pattern of biliary complications in an evolving liver transplant unit
    Background:Biliary complications remain a significant cause of morbidity following liver transplantation. This series of 640 Liver transplant recipients with a blend of living and deceased donor transplants was analyzed to determine the incidence, risk factors, management protocol and outcomes in these patients. Methods:Review of a prospectively collected database of transplant recipients operated between Aug 2009 and June 2016 was performed. Patients were divided into those with and without biliary complications and data was analyzed. Results:640 liver transplant recipients from both living (481) and deceased donors (159) were evaluated for biliary complications. The overall incidence of biliary complications was 13.7%. It reduced from 23% to 5% (p=0.003) over a 6‐year period. Risk factors for biliary complications on multivariate analysis were live donor liver transplantation, prolonged time to rearterialisation, recipient age above 16 years, prolonged cold ischemia time (CIT) after deceased donor liver transplantation and biliary reconstruction performed by anyone but the senior author. One‐fifth of bile leaks progressed to strictures and 40% of strictures followed leaks. Endoscopic therapy resolved 60% of the strictures. Surgical repair of strictures was successful in 90% of those in whom endoscopy failed, those who could not undertake the follow‐up schedules endoscopic therapy entails, and those presenting with late strictures. Biliary complications significantly prolonged hospital stay but did not alter survival after liver transplantation. Conclusions: Biliary complications affect 1 in 7 recipients, although they are not associated with increased mortality. The frequency of these complications are influenced by potentially modifiable factors like evolving surgical expertise and CIT. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Jeudi 02 fvrier 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
    PTEN‐β‐Catenin Signaling Modulates Regulatory T Cells and Inflammatory Responses in Mouse Liver Ischemia and Reperfusion Injury
    The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) 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 and reperfusion injury (IRI). We found that mice with myeloid specific PTEN knockout (PTENM‐KO) exhibited reduced liver damage as evidenced by decreased levels of serum ALT, intrahepatic macrophage trafficking, and pro‐inflammatory mediators compared to the PTEN‐proficient (PTENFL/FL) controls. Disruption of myeloid PTEN activated β‐catenin, which in turn promoted PPARγ‐mediated Jagged‐1/Notch signaling and induced Foxp3+ Tregs while inhibiting Th17 cells. However, blocking of Notch signaling by inhibiting γ‐secretase reversed myeloid PTEN deficiency‐mediated protection in IR‐triggered liver inflammation with reduced Foxp3+ and increased RORγt‐mediated IL‐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 co‐cultures. 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. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 30 janvier 2017
    J. Y. Choi, J. I. Yu, H. C. Park, C. H. D. Kwon, J. M. Kim, J.‐W. Joh, G.S. Choi, J. B. Park, S. J. Kim, S.H. Lee, W.‐T. Cho, K.W. Lee, B.‐G. Na, D.K. Oh, N.R. Lee, C.W. Cho, S. Lee, S.‐K. Lee
    The possibility of radiotherapy as downstaging to living donor liver transplantation for hepatocellular carcinoma with portal vein tumor thrombus
    Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) are difficult to manage with very poor survival and due to universal recurrence after liver transplantation, they have been excluded from indication. Conformer radiation therapy (RT) has been shown to be effective in the treatment of HCC but only few trials have been reported as bridge to liver transplantation (LT) in HCC with PVTT. The purpose of our study was to evaluate the possibility of applying living donor liver transplantation (LDLT) following successful downstaging using RT in advanced HCC with PVTT. Among 1360 patients who received LT at our institution between May 1996 and March 2013, 5 received RT and they were compared with a propensity score matched group of 10 patients receiving RT alone according to sex, age, tumor size and number, dose of RT, level of AFP and location of PVTT. Objective tumor response after RT was evaluated with CT and/or MRI according to modified RECIST criteria. There is no difference in clinical characteristics between both groups. Two recipients showed disease progression, but in RT alone group, all patients are shown tumor ingrowths or intra‐, extra‐hepatic metastasis. LDLT following RT group's OS was 1055 days and that of RT alone group's was 367 days with significant statistically difference. Conclusion: LDLT following RT can be treatment of choice for PVTT in selective patients like solitary HCC with below Vp3 PVTT and good tumor response, and we suggest that this warrants further testing in a randomized, controlled, multi‐center trial. And when doing bile duct anastomosis in RT recipients, hepaticojejunostomy was recommended to prevent biliary complication. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 30 janvier 2017
    Daniel Katz, Jeron Zerillo, Sang Kim, Bryan Hill, Ryan Wang, Andrew Goldberg, Samuel DeMaria
    Serious Gaming for Orthotopic Liver Transplant Anesthesiology: A Randomized Control Trial
    Anesthetic management of orthotopic liver transplantation (OLT) is complex. Given the unequal distributions of liver transplant surgeries performed at different centers, anesthesiology providers receive relatively uneven OLT training and exposure. One well‐suited modality for OLT training is the “serious game”, an interactive application created for the purpose of imparting knowledge or skills, while leveraging the self‐motivating elements of video games. We therefore developed a serious game designed to teach best practices for the anesthetic management of a standard OLT and determined if the game would improve resident performance in a simulated OLT. 44 residents on the liver transplant rotation were randomized to either the Gaming Group (GG) or the Control Group (CG) prior to their introductory simulation. Both groups were given access to the same educational materials and literature during their rotation but the Gaming Group also had access to the OLT Trainer. Performance on the simulations were recorded on a standardized grading rubric. Both groups experienced an increase in score relative to baseline that was statistically significant at every stage. The improvements in scores were greater for the GG participants than the CG participants. Overall score improvement between the GG and CG (Mean (SD)) was statistically significant (GG: 7.95 (3.65), CG: 4.8 (4.48) p=0.02), as were scores for pre‐operative assessment (GG: 2.67 (2.09), CG: 1.17 (1.43) p=0.01) and anhepatic phase (GG: 1.62 (1.01), CG: 0.75 (1.28) p=0.02). 81% of residents with game access were “very satisfied” or “satisfied” with the game overall. Conclusion: Adding a serious game to an existing educational curriculum for liver transplant anesthesia resulted in significant learning gains for rotating anesthesia residents. The intervention was straight‐forward to implement and cost‐effective. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 30 janvier 2017
    Siddharth Sood, Craig Haifer, Lijia Yu, Julie Pavlovic, Leonid Churilov, Paul J. Gow, Robert M. Jones, Peter W. Angus, Kumar Visvanathan, Adam G. Testro
    A novel immune function biomarker identifies patients at risk of clinical events early following liver transplantation
    Balancing immunosuppression after liver transplant is difficult, with clinical events common. We investigate whether a novel immune biomarker based on a laboratory platform with widespread availability that measures interferon gamma (IFNγ) after stimulation with a lyophilized ball containing an adaptive and innate immune stimulant can predict events following transplantation. 75 adult transplant recipients were prospectively monitored in a blinded, observational study. 55/75 (73.3%) patients experienced a total 89 clinical events. Most events occurred within the first month. Low week 1 (W1) results were significantly associated with risk of early infection (AUROC 0.74, p=0.008). IFNγ≤1.30IU/mL (LR+ 1.93, sensitivity 71.4%, specificity 63.0%) was associated with the highest risk for infection with minimal rejection risk. Nearly half the cohort (27/60, 45.0%) expressed IFNγ≤1.30IU/mL. Moreover, an elevated W1 result was significantly associated with the risk of rejection within the first month post‐transplant (AUROC 0.77, p=0.002), but no episodes of infection. On multivariate logistic regression, IFNγ≥4.49IU/mL (OR 4.75) may be an independent predictor of rejection (p=0.05). Conclusion: Low IFNγ suggesting over‐suppression is associated with infections, while high IFNγ indicating under‐suppression is associated with rejection. This assay offers the potential to allow individualisation and optimisation of immunosuppression that could fundamentally alter the way patients are managed following transplantation. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Lundi 30 janvier 2017
    Jian Sun, Enshuang Guo, Jiankun Yang, Yan Yang, Shenpei Liu, Jifa Hu, Xiaojing Jiang, Olaf Dirsch, Uta Dahmen, Wei Dong, Anding Liu
    Carbon monoxide ameliorates hepatic ischemia/reperfusion injury via sirtuin1‐mediated deacetylation of HMGB1 in rats
    Carbon monoxide (CO) exerts protective effects on hepatic ischemia/reperfusion (I/R) injury, but the underlying molecular mechanisms are not fully understood. High mobility group box 1 (HMGB1) is an important mediator of injury and inflammation in hepatic I/R injury. Here, we investigated whether CO could attenuate hepatic I/R injury via inhibition of HMGB1 release, particularly through sirtuin 1 (SIRT1). CO was released by treatment with CO‐releasing molecule (CORM)‐2. CORM‐2‐delivered CO ameliorated hepatic I/R injury, as indicated by lower serum aminotransferase levels, lower hepatic inflammatory responses and less severe I/R‐associated histopathologic changes. Treatment with CORM‐2 significantly inhibited I/R injury‐induced HMGB1 translocation and release. SIRT1 expression was increased by CORM‐2 pretreatment. When CORM‐2‐induced SIRT1 expression was inhibited using EX527, HMGB1 translocation and release were increased and hepatic I/R injury was worsened, while SIRT1 activation by resveratrol reversed this trend. In vitro, CORM‐2 reduced hypoxia/reoxygenation‐induced HMGB1 translocation and release, which were blocked by SIRT1 inhibition using EX527 or SIRT1 small interfering RNA both in AML12 cells and RAW264.7 macrophages. Moreover, SIRT1 directly interacted with and deacetylated HMGB1. I/R injury increased HMGB1 acetylation, which was abolished by CORM‐2 treatment via SIRT1. Conclusion: These results suggest that CO may increase SIRT1 expression, which may decrease HMGB1 acetylation and subsequently reduce its translocation and release, thereby protecting against hepatic I/R injury. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 25 janvier 2017
    Ina Jochmans, Nicolas Meurisse, Arne Neirynck, Marleen Verhaegen, Diethard Monbaliu, Jacques Pirenne
    Hepatic ischemia‐reperfusion injury associates with acute kidney injury in liver transplantation: Prospective cohort study
    Solid clinical prospective studies investigating the association between hepatic ischemia reperfusion injury and acute kidney injury after liver transplantation are missing. Hepatic ischemia reperfusion injury ‐reflected by transaminase release‐ induces acute kidney injury in rodents and retrospective studies suggest a similar association in man. This prospective cohort study determined risk factors for acute kidney injury in 80 adult liver‐only recipients. Acute kidney injury ‐defined by RIFLE‐criteria‐ developed in 21 (26%) recipients at 12 hours postreperfusion [inter quartile range: 6 hours‐postoperative day 1]; 13 progressed from “Risk” to “Injury”; 5 to “Failure”. In acute kidney injury patients, creatinine increased during liver transplantation and was higher vs. baseline at 6h to postoperative day 4 while peroperative creatinine remained stable in those without acute kidney injury. Plasma heart‐fatty acid binding protein was higher 12 hours postreperfusion in acute kidney injury patients, though urinary kidney‐injury‐molecule‐1 and neutrophil gelatinase associated lipocalin were similar between those with or without acute kidney injury. Peak aspartate aminotransferase, occurring at 6 hours, was the only independent risk factor for acute kidney injury [adjusted odds ratio 2.42 (1.24‐4.91)]. Early allograft dysfunction occurred more frequently in acute kidney injury‐patients and intensive care and hospital stays were longer. Patient survival at 1y was 90% in those with acute kidney injury vs. 98% in those without acute kidney injury. Chronic kidney disease stage ≥2 at 1y was more frequent in patients who had had acute kidney injury (89% vs. 58%, respectively). Conclusion: Acute kidney injury is initiated early after liver reperfusion and its association with peak aspartate aminotransferase suggests hepatic ischemia reperfusion injury as a determinant. Identifying operating mechanisms is critical to target interventions and reduce associated morbidity. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Vendredi 20 janvier 2017
    Giuseppe Indolfi, Lorenzo D'Antiga
    Treatment of Hepatitis C Virus Infection in Children: Time for Action

    Date de mise en ligne : Jeudi 19 janvier 2017
    Kyoji Ito, Nobuhisa Akamatsu, Norihiro Kokudo
    Simultaneous splenectomy in Living Donor Liver Transplantation In Reply to Athanasiou and colleagues

    Date de mise en ligne : Jeudi 19 janvier 2017
    Antonios Athanasiou, Demetrios Moris, Christos Damaskos, Eleftherios Spartalis
    Splenectomy is not indicated in living donor liver transplantation

    Date de mise en ligne : Jeudi 19 janvier 2017
    Ibrahim Altraif
    Sofosbuvir plus ledipasvir for recurrent hepatitis C in liver transplant recipients

    Date de mise en ligne : Mardi 17 janvier 2017
    David Goldberg
    Response to, “The Devil Certainly IS in the Details – Defining Geographic Disparity

    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 10 janvier 2017
    Chris E. Freise
    Vascular Complication Rates in Living Donor Liver Transplantation: How Low Can We Go?

    Date de mise en ligne : Mardi 10 janvier 2017
    Mettu Srinivas Reddy, Mohamed Rela
    Porto‐systemic Collaterals in Living Donor Liver Transplantation. What's all the fuss about?
    Porto‐systemic collaterals are a common finding in patients with cirrhosis undergoing liver transplantation. Recently, there has been renewed interest regarding their significance in the setting of living donor liver transplantation (LDLT) due to concerns of graft hypo or hyper‐perfusion and its impact on early post‐transplant outcomes. Presence of these collaterals has greater significance in the LDLT setting when compared to deceased donor liver transplant setting as dictated by the difference in the physiology of partial liver grafts. We discuss current thinking of portal flow dynamics and the techniques for dealing with this clinical problem. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mardi 10 janvier 2017
    Carlo Pulitano, David Joseph, Charbel Sandroussi, Deborah Verran, Phong Ho, Ashe Debiasio, Adriano Luongo, Geoffrey W. McCaughan, Nicholas Shackel, Michael Crawford
    Post‐Reperfusion Microcirculatory Derangements after Liver Transplantation: Relationship to Hemodynamics, Serum Mediators, and Outcome
    Introduction: Despite the growing data supporting the role of microcirculation in regulating liver function, little of this knowledge has been translated into clinical practice. The aim of this study is to quantify hepatic microcirculation in‐vivo using sidestream dark‐field (SDF) imaging and correlate these finding with hepatic blood flow, hemodynamic parameters, and soluble mediators. Methods: Post‐reperfusion hepatic microcirculation was assessed using SDF imaging. Hepatic microcirculation measurements included: functional sinusoidal density (FSD) (cm/cm2), sinusoidal diameter (μm), red blood cell velocity (RBCV) (μm/s), volumetric blood flow (VBF) (pl/s), and flow heterogeneity index (FH). The serum concentrations of Endothelin‐1 (ET‐1), and other inflammatory markers were analyzed with Luminex technology. Portal venous and hepatic artery flows were measured using a flowmeter. Results: Twenty‐eight patients undergoing cadaveric liver transplantations have been included in this study. Early allograft dysfunction (EAD) occurred in 7 (25%) patients and was associated with microcirculatory dysfunction. Low arterial and portal flow, high dose of inotropes, cold ischemia time, steatosis, and high ET‐1 levels were all associated with impaired microcirculation. The time interval between portal venous and hepatic arterial reperfusion significantly correlated with the changes of the liver grafts' microcirculation. EAD patients tended to have higher serum levels of ET‐1 on POD 1, 2, 5, and 7 (all P < 0.01). Serum levels of ET‐1 correlated significantly with microcirculation parameters. Conclusions: Post‐reperfusion hepatic microcirculation is a determinant of organ dysfunction after liver reperfusion and could be used to identify very early patients at risk of EAD. This article is protected by copyright. All rights reserved.

    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 : Mardi 27 dcembre 2016
    K.A. McLean, J. Camilleri‐Brennan, S.R. Knight, T. Drake, R. Ots, C.A. Shaw, S.J. Wigmore, E.M. Harrison
    Decision modelling in donation after circulatory death (DCD) liver transplantation
    Introduction: Donation after circulatory death (DCD) liver allografts are increasingly used for transplantation. However, the post‐transplantation clinical and quality of life outcomes of DCD recipients are traditionally considered to be inferior compared with donation after brain death (DBD) allograft recipients. Decision making for such marginal organs can be difficult. This study investigated the optimal decision to accept or decline a DCD liver allograft for a patient based on their current health. Methods: A Markov decision process model was constructed to predict the 5 year clinical course of patients on the liver transplant waiting list. Clinical outcomes were determined from the UK Transplant registry or appropriate literature. Quality‐adjusted life years (QALYs) were determined using the condition‐specific “Short form of liver disease quality of life” (SF‐LDQOL) questionnaire. Results: There were 293/374 (78.3%) eligible patients who completed the SF‐LDQOL questionnaire. Seventy‐three respondents (24.9%) were pre‐transplant and 220 were post‐transplant (DBD‐recipient, 57.0%; DCD‐recipient, 10.2%; re‐transplant recipient, 7.9%). Predictive modelling indicated that quality‐adjusted life years (QALYs) gained at 5 years were significantly higher in DCD‐recipients (3.77, 95% CI=3.44‐4.10) compared to those who remained on the waiting list for a DBD transplant with model of end‐stage liver disease (MELD) scores of 15‐20 (3.36, 95% CI=3.28‐3.43), or >20 (3.07, 95% CI=3.00‐3.14). There was no significant advantage for individuals with MELD scores <15 (3.55, 95% CI=3.47‐3.63). Conclusion: This model predicts that patients on the UK liver transplant waiting list with MELD scores >15 should receive an offered DCD allograft based on the QALYs gained at 5 years. This analysis only accounts for donor‐recipient risk pairings seen in current practice. The optimal decision for patients with MELD scores <15 remains unclear, however a survival benefit was observed when a DCD organ was accepted. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mardi 27 dcembre 2016
    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 5,080 adults underwent primary transplantation for PSC during this period, and of the 1,803 who experienced graft failure, 762 were relisted, and 636 underwent retransplantation. Younger patients and patients with graft failure due to vascular thrombosis or biliary complications were more likely to be relisted, while those with Medicaid insurance or graft failure due to infection were less likely. Both five‐year graft and patient survival after retransplantation were inferior to primary transplantation (p=0.001). Five‐year survival after retransplantation for disease recurrence, 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. Conclusion: While survival after liver retransplantation in patients with PSC was overall inferior to primary transplantation, outcomes after retransplantation for PSC recurrence were similar to primary transplantation at five years. Retransplantation may therefore represent a treatment option with the potential for excellent outcomes in patients with recurrence of PSC in the appropriate clinical circumstances. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mardi 27 dcembre 2016
    Nicolas Goldaracena, Juan Echeverri, Markus Selzner
    Reply to 16‐663

    Date de mise en ligne : Jeudi 22 dcembre 2016
    Henri Bismuth
    To the editor

    Date de mise en ligne : Jeudi 22 dcembre 2016
    Koen Huysentruyt, Xavier Stephenne, Sharat Varma, Isabelle Scheers, Gisèle Leclercq, Françoise Smets, Etienne Sokal
    Sofosbuvir/ledipasvir and ribavirin tolerability and efficacy in pediatric liver transplant recipients

    Date de mise en ligne : Jeudi 22 dcembre 2016
    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
    The 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 : Jeudi 22 dcembre 2016
    George N. Ioannou
    Transplant‐Related Survival Benefit Should Influence Prioritization for Liver Transplantation Especially in Patients with Hepatocellular Carcinoma
    Transplant‐related survival benefit is calculated as the difference between life expectancy with transplantation and life expectancy without transplantation. Determining eligibility and prioritization for liver transplantation based on the highest survival benefit is a superior strategy to prioritization based on the highest urgency (i.e. the highest waitlist mortality) or the highest utility (i.e. the highest post‐transplant survival) because prioritization based on the highest survival benefit maximizes the overall life expectancy of all patients in need of liver transplantation. Although the MELD‐based prioritization system was designed as an urgency‐based system, in practice it functions to a large extent as a survival benefit‐based system, when the natural MELD score is used without exceptions. Survival benefit considerations should be used to determine the consequences of deviating from prioritization based on the natural MELD score, such as when exception points are awarded to patients with hepatocellular carcinoma (HCC) that are independent of MELD score or tumor burden, or the appropriateness of expanding eligibility for transplantation. The most promising application of survival benefit–based prioritization would be to replace the current system of prioritization of patients with HCC by one that uses their natural MELD score and tumor characteristics such as HCC tumor burden, serum AFP level and response to locoregional therapies to predict the impact on survival benefit caused by the presence of HCC and adjust the natural MELD score for prioritization accordingly. This article is protected by copyright. All rights reserved.

    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 : Jeudi 22 dcembre 2016
    Jens G. Brockmann, Thomas Vogel, Constantin Coussios, Peter J. Friend
    Liver splitting during normothermic organ preservation
    Classical split liver transplantation has proved a successful means of transplanting children with size‐matched organs without reducing the adult cadaveric liver pool. However, the conventional technique of liver splitting after retrieval (ex situ) implies either increasing the ischaemia time of one graft or the logistic problems of simultaneous transplants in a single institution. Splitting the liver in the donor (in situ splitting) minimises cold ischaemia but greatly increases the operating time in the donor hospital and requires highly specialised hepatobiliary expertise at time of organ donation. Normothermic liver preservation may enable longer preservation times without detrimental effects. In a pre‐clinical proof of concept study, a classical split was performed of a human liver (declined for clinical use) during normothermic perfusion. After completion of the split the extended right liver lobe was maintained on the perfusion device. In conclusion this new method might expand the scope of liver splitting and increase the number of such organs transplanted. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Vendredi 09 dcembre 2016
    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 09 dcembre 2016
    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 09 dcembre 2016
    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 (HOTS)
    Hepatitis C (HCV) infection is the leading cause of liver disease in hemophilia. In those with HIV/HCV co‐infection, the rate of liver disease progression is greater than in HCV mono‐infected individuals. Despite antiretroviral therapy which slows HCV liver disease progression, some require transplantation. Whether transplant outcomes are worse in hemophilic (H) than non‐hemophilic (NH) candidates is unknown. In order to determine rates and predictors of pre‐ and post‐transplant survival, we conducted a retrospective observational study utilizing United Network for Organ Sharing (UNOS) national transplant registry data, comparing HCV+ H and NH candidates. We identified 2,502 HCV+ liver transplant candidates from eight U.S. university‐based transplant centers, between January 1, 2004 to December 31, 2010, including 144 HIV+ (6%) and 2,358 HIV‐; 36 H (1%) and 2,466 NH; 1,213 (48%) transplanted and 1,289 not transplanted. Other than male predominance and younger age, each p<0.001, baseline data were comparable between H and NH. In univariate analysis, 90‐day pre‐transplant mortality was associated with higher baseline MELD, HR=1.15, p<0.001, lower baseline platelet count, HR=1.11 per 25k/µL, p=0.04, and having HIV/HCV+ hemophilia, p=0.003. In multivariate analysis, pre‐transplant mortality was associated with higher MELD (p<0.001) and was significantly greater in HIV+ than HIV‐ groups (p=0.001), but did not differ between HIV+ H and NH, HR=1.7, p=0.36. Among HIV/HCV+, post‐transplant mortality was similar between H and NH, despite lower CD4 in H, p=0.04. Conclusions: 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. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Jeudi 24 novembre 2016
    Davide Ghinolfi, Laura Caponi, Lorella Marselli, Daniele Pezzati, Maria Franzini, Paolo De Simone, Vanna Fierabracci, Piero Marchetti, Aldo Paolicchi, Franco Filipponi
    Considerations about the importance of cytokines expression for optimizing liver graft metabolism during normothermic machine perfusion

    Date de mise en ligne : Mercredi 23 novembre 2016
    A.R. Shiraz, M.A. Nayeem, S. Agarwal, N. Goyal, S. Gupta
    Vascular Complications in Living Donor Liver Transplantation at a high volume Centre: Evolving Protocols and Trends Observed over 10 years
    Vascular complications continue to have devastating effect; although their nature, incidence and outcome might have actually changed with increasing experience and proficiency in high volume centers. Aim was to analyze the trends observed in vascular complications with changing protocols in adult and pediatric‐ living donor liver transplantation (A‐LDLT and P‐LDLT) over 10 years in two time frames in terms of nature, incidence and outcome. It is a retrospective analysis of 391 (Group I= Jan. 2006‐ Dec.2010) and 741 (Group II= Jan. 2011‐ Oct. 2013) patients. With a minimum follow up of 2 years, incidence of hepatic artery thrombosis (HAT) in adults has reduced significantly from 2.2% in Group I to 0.5% to Group II, P = 0.02. In Group II non‐significantly more adult patients 75% with HAT could be salvaged compared to only 25% patients in Group I, P = 0.12. But HAT in children had 100% mortality. Incidence of portal vein thrombosis (PVT) in complicated transplants in two eras has remained same P = 0.2 so has its mortality. Thrombosis rate of neo‐ middle hepatic vein (Neo‐MHV) has significantly reduced in Group II (P = 0.01). The incidence of HAT particularly in adults has decreased significantly though PVT has continued to puzzle surgeons in complicated transplants. In high volume centers, increasing proficiency, technical modifications, early diagnosis and multimodality treatment is the key to decrease overall morbidity and mortality due to vascular complications. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Jeudi 03 novembre 2016
    Seong Hoon Kim, Eung Chang Lee, Seung Duk Lee, Sang Jae Park
    Ligation & Cut as a Method for Bile Duct Division in Living Donor Right Hepatectomy
    The importance of bile duct division cannot be overemphasized in living donor surgery. The ligation & cut (LC) as a method for bile duct division in living donor right hepatectomy (LDRH) has never been reported. The purpose of this study was to introduce the LC method of bile duct division in LDRH. All LDRH donors were identified through a prospectively maintained database at the authors' institution between September 2009 and March 2013, and the two methods, LC and cut & oversewing (CO), were compared both in terms of donor and recipient outcomes of right lobe living donor liver transplantation (LDLT). In the LC method, after complete parenchymal transection, the right hepatic duct was dissected in the Glisson's sheath and ligated just at the right side of the confluence, and then the right side of ligature was cut. The LC and CO methods were performed in 109 and 134 donors, respectively. Bile duct division time (p<0.001) and operative time (p<0.001) were significantly shorter in group LC than in group CO. With a median follow‐up of 60.2 months, biliary complication rate was lower in group LC than in group CO (0 vs.5.2%; p=0.02), but with no significant difference between the recipient groups. All donors made a complete recovery. Conclusion: The bile duct of living donors can be dissected safely from the Glisson's sheath, and the LC method facilitates bile duct division and has a lower incidence of biliary complication in LDRH without compromising the recipient outcomes. This article is protected by copyright. All rights reserved.

    Date de mise en ligne : Mercredi 01 avril 2015

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Issue Information
    Issue Information

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Shari Rogal, Mary Amanda Dew, Andrea DiMartini
    High‐dose opioid use and liver transplantation: An underestimated problem?

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Nicolas Goldaracena, Nazia Selzner, Markus Selzner
    Living donation to the extreme: Saving a life not once, but twice

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Jodie A. Barkin, Jamie S. Barkin
    Presence of small pancreatic cystic lesions should not preclude liver transplantation

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Mariya L. Samoylova, Kenneth E. Covinsky, Marta Haftek, Selena Kuo, John P. Roberts, Jennifer C. Lai
    Disability in patients with end‐stage liver disease: Results from the functional assessment in liver transplantation study
    Cirrhosis leads to sarcopenia and functional decline that can severely impact one's ability to function at home and in society. Self‐reported disability scales to quantify disability—Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL)—are validated to predict mortality in older adults. To evaluate disability in liver transplantation (LT) candidates and quantify its impact on outcomes, consecutive outpatients ≥18 years listed for LT with laboratory Model for End‐Stage Liver Disease scores of ≥12 at a single high‐volume US LT center were assessed for ADLs and IADLs during clinic visits. Multivariate competing risk models explored the effect of disabilities on wait‐list mortality (death or delisting for illness). Of 458 patients, 36% were women, median (interquartile range [IQR]) age was 60 years (IQR, 54‐64 years), and initial Model for End‐Stage Liver Disease–Sodium (MELD‐Na) was 17 (IQR 14‐20). At first visit, 31% had lost ≥ 1 ADL, and 40% had lost ≥ 1 IADL. The most prevalent ADL deficits lost were continence (22%), dressing (12%), and transferring (11%); the most prevalent IADLs lost were shopping (28%), food preparation (23%), and medication management (22%). After adjustment for age, MELD‐Na, and encephalopathy, dressing (subdistribution hazard ratio [SHR], 1.7; 95% confidence interval [CI], 1.0‐2.8; P = 0.04), toileting (SHR, 1.9; 95% CI, 1.1‐3.5; P = 0.03), transferring (SHR, 1.9; 95% CI, 1.1‐3.0; P = 0.009), housekeeping (SHR, 1.8; 95% CI, 1.2‐3.0; P = 0.009), and laundry (SHR, 2.2; 95% CI, 1.3‐3.5; P = 0.002) remained independent predictors of wait‐list mortality. In conclusion, ADL/IADL deficits are common in LT candidates. LT candidates would benefit from chronic disease management programs developed to address the impact of cirrhosis on their daily lives. Liver Transplantation 23 292–298 2017 AASLD.

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Narendra Battula, Trevor W. Reichman, Yamah Amiri, Ian C. Carmody, Gretchen Galliano, John Seal, Emily Bugeaud, Humberto Bohorquez, David Bruce, Ari Cohen, George E. Loss
    Outcomes utilizing imported liver grafts for recipients with hepatocellular carcinoma
    Liver transplantation (LT) offers the best chance of survival in selected patients with hepatocellular carcinoma (HCC). Wait‐list mortality or dropout due to tumor progression can be significant, and therefore, timely transplantation is critical. Liver grafts discarded by outside organ procurement organizations are a potential source of grafts for low Model for End‐Stage Liver Disease tumor patients. The primary aim of this study was to assess the disease‐free and overall survival of patients with HCC transplanted with imported liver grafts (ILGs). Review of all patients transplanted for HCC between June 2005 and December 2014 was performed. Data on demographics, survival, and HCC recurrence were analyzed. During this time period, 59 out of 190 (31%) recipients with HCC received ILG. Of these 59 grafts, 54 were imported from within the region and 5 were from national offers (outside the region). The mean cold ischemia time for local liver grafts (LLGs) was 4.1 ± 1.5 hours versus 5.1 ± 1.4 hours for ILG (P < 0.001). The 1‐, 3‐, and 5‐year patient survival was 90%, 85%, and 83% and 85%, 80%, and 79% for LLG and ILG (P = 0.08), respectively. The observed disease recurrence rate for both LLG and ILG recipients was equivalent. The median wait‐list time for HCC recipients was 43 days (range, 2‐1167 days). In conclusion, with careful graft assessment, the use of ILGs results in comparable outcomes following LT and no increased risk of HCC recurrence. Use of ILGs maximizes the donor pool and results in a higher rate of transplantation for HCC recipients. Liver Transplantation 23 299–304 2017 AASLD.

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Henry B. Randall, Tarek Alhamad, Mark A. Schnitzler, Zidong Zhang, Sophia Ford‐Glanton, David A. Axelrod, Dorry L. Segev, Bertram L. Kasiske, Gregory P. Hess, Hui Yuan, Rosemary Ouseph, Krista L. Lentine
    Survival implications of opioid use before and after liver transplantation
    Implications of prescription opioid use for outcomes after liver transplantation (LT) have not been described. We integrated national transplant registry data with records from a large pharmaceutical claims clearinghouse (2008‐2014; n = 29,673). Opioid fills on the waiting list were normalized to morphine equivalents (MEs), and exposure was categorized as follows: > 0‐2 ME/day (level 1), > 2‐10 ME/day (level 2), > 10‐70 ME/day (level 3), and >70 ME/day (level 4). Associations (adjusted hazard ratio [aHR], 95% LCL aHR 95% UCL) of pretransplant ME level with patient and graft survival over 5 years after transplant were quantified by multivariate Cox regression including adjustment for recipient, donor, and transplant factors, as well as propensity adjustment for opioid use. Overall, 9.3% of recipients filled opioids on the waiting list. Compared with no use, level 3 (aHR and 4 (aHR 1.161.521.98) opioid use during listing were associated with increased mortality over 5 years after transplant. These associations were driven by risk after the first transplant anniversary, such that mortality >1‐5 years increased in a graded manner with higher use on the waiting list (level 2, aHR,; level 3, aHR, 1.081.381.77; level 4, aHR, 1.492.012.72). Similar patterns occurred for graft failure. Of recipients with the highest level of opioids on the waiting list, 65% had level 3 or 4 use in the first year after transplant, including 55% with use at these levels from day 90‐365 after transplant. Opioid use in the first year after transplant also bore graded associations with subsequent death and graft loss >1‐5 years after transplant. Opioid use history may be relevant in assessing and providing care to LT candidates. Liver Transplantation 23 305–314 2017 AASLD.

    Date de mise en ligne : Lundi 06 fvrier 2017
    Kumiko Kitajima, Yuichi Ogawa, Katsuyuki Miki, Kotaro Kai, Akihito Sannomiya, Kazuhiro Iwadoh, Toru Murakami, Ichiro Koyama, Ichiro Nakajima, Shohei Fuchinoue
    Longterm renal allograft survival after sequential liver‐kidney transplantation from a single living donor
    Combined liver‐kidney transplantation (CLKT) is well established as a definitive therapy with the potential to provide complete recovery for certain liver‐kidney diseases, although the results might be contingent on the cause of transplantation. The purposes of the present study were to review the longterm outcome of renal allografts in CLKT patients from single living donors and to investigate the beneficial factors, compared with solitary renal transplantation. Thirteen patients underwent sequential liver transplantation (LT) and kidney transplantation (KT) from single living donors. The indications for KT were oxaluria (n = 7), autosomal recessive polycystic disease (n = 3), and others (n = 3). The same immunosuppressive regimen used after LT was also used after KT. KT was performed between 1.7 and 47.0 months after the LT. The overall patient survival rate was 92.3% at 10 years. In 12 of the 13 surviving patients, the renal allografts were found to be functioning in 11 patients after a mean follow‐up period of 103.6 months. The death‐censored renal allograft survival rate at 10 years was 100%, which was better than that of KT alone (84.9%) in Japan. Immunological protection conferred by the preceding liver allograft may have contributed to the longterm outcomes of the renal allografts. In addition, the donation of double organs from a single living and related donor may have a favorable impact on the graft survival rate. In the future, investigations of factors affecting the longterm outcome of renal allografts, including details of the involvement of de novo donor‐specific antibody, will be needed. Liver Transplantation 23 315–323 2017 AASLD.

    Date de mise en ligne : Mercredi 08 fvrier 2017
    Sirachat Vidhyarkorn, Surachate Siripongsakun, Jennifer Yu, James Sayre, Vatche G. Agopian, Francisco Durazo, David S. Lu
    Longterm follow‐up of small pancreatic cystic lesions in liver transplant recipients
    Incidental small pancreatic cystic lesions (PCLs) are often found on preoperative imaging in patients undergoing orthotopic liver transplantation (OLT). Although these are considered benign or of low malignant potential, the influence of immunosuppression after OLT may be of concern. The aim of this study was to observe the longterm outcome of these small PCLs in post‐OLT patients. An institutional OLT database of 1778 consecutive OLT patients from January 2000 to December 2010 was analyzed. Computed tomography, magnetic resonance imaging, or endoscopic ultrasound at the time of OLT and all subsequent imaging, cytology, fluid analysis of PCLs, and patient status were evaluated. A total of 70 patients with 182 PCLs, of benign or low malignant potential, were identified with a mean follow‐up time of 64 months. At initial diagnosis of PCLs in 48 patients, 7 branch duct–type intraductal papillary mucinous neoplasms (B‐IPMNs), 1 serous cystadenoma (SCA), and 40 nonspecific benign cysts were identified. Final diagnosis at the end of the follow‐up revealed 16 B‐IPMNs, 3 SCAs, and a mixed acinar‐neuroendocrine carcinoma, in which the latter developed 9 years after initial diagnosis of B‐IPMN. During the follow‐up time, average increase in size and number of PCLs were 4.5 mm and 1.4, respectively (P < 0.001 for both). The majority of incidental PCLs in OLT patients showed an indolent behavior despite immunosuppression. Risk of malignancy development was very low and comparable with normal population. Liver Transplantation 23 324–329 2017 AASLD.

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Dong‐Hwan Jung, Shin Hwang, Gi‐Won Song, Chul‐Soo Ahn, Deok‐Bog Moon, Ki‐Hun Kim, Tae‐Yong Ha, Gil‐Chun Park, Seung‐Mo Hong, Wan‐Jun Kim, Woo‐Hyoung Kang, Seok‐Hwan Kim, Eun Sil Yu, Sung‐Gyu Lee
    Longterm prognosis of combined hepatocellular carcinoma‐cholangiocarcinoma following liver transplantation and resection
    Combined hepatocellular carcinoma–cholangiocarcinoma (cHCC‐CC) is a rare disease. We investigated the clinicopathological features of cHCC‐CC and compared the longterm outcomes following liver transplantation (LT) and hepatic resection (HR). We identified 32 LT patients with cHCC‐CC through an institutional database search. The HR control group (n = 100) was selected through propensity score‐matching. The incidence of cHCC‐CC among all adult LT patients was 1.0%. Mean patient age was 53.4 ± 6.7 years, and 26 patients were male. Thirty patients had hepatitis B virus infection. All patients of cHCC‐CC were diagnosed incidentally in the explanted livers. Mean tumor diameter was 2.5 ± 1.3 cm, and 28 patients had single tumors. Tumor stage was stage I in 23 and II in 9. Concurrent hepatocellular carcinoma (HCC) was detected in 12 patients with stage I in 5 and II in 7. Mean tumor diameter was 1.9 ± 1.2 cm, and 5 had single tumors. Tumor recurrence and survival rates were 15.6% and 84.4% at 1 year and 32.2% and 65.8% at 5 years, respectively. Patients with very early stage cHCC‐CC (1 or 2 tumors ≤ 2.0 cm) showed 13.3% tumor recurrence and 93.3% patient survival rates at 5 years, which were significantly improved than those with advanced tumors (P = 0.002). Tumor recurrence and survival rates did not differ significantly between the LT and HR control groups (P = 0.22 and P = 0.91, respectively); however, postrecurrence patient survival did (P = 0.016). In conclusion, cHCC‐CC is rarely diagnosed following LT, and one‐third of such patients have concurrent HCC. The longterm posttransplant prognosis was similar following LT and HR. Very early cHCC‐CC resulted in favorable posttransplant prognosis, thus this selection condition can be prudently considered for LT indication. Liver Transplantation 23 330–341 2017 AASLD.

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Kristopher P. Croome, David D. Lee, Dana K. Perry, Justin M. Burns, Justin H. Nguyen, Andrew P. Keaveny, C. Burcin Taner
    Comparison of longterm outcomes and quality of life in recipients of donation after cardiac death liver grafts with a propensity‐matched cohort
    The use of liver grafts from donation after cardiac death (DCD) has been limited due to the increased rate of graft failure, mostly related to ischemic cholangiopathy (IC). It is our hypothesis that longterm outcomes and quality of life (QOL) similar to patients undergoing liver transplantation (LT) with donation after brain death (DBD) can be achieved. Clinical outcomes of all patients undergoing DCD LT (n = 300) between 1998 and 2015 were compared with a propensity score–matched cohort of patients undergoing DBD LT (n = 300). Patients were contacted for a follow‐up questionnaire and short‐form (SF)–12 QOL Survey administration. Median follow‐up was >5 years. Graft survival at 1‐, 3‐, and 5‐years was 83.8%, 75.5%, and 70.1% in the DCD LT group and 88.4%, 80.3%, and 73.9% in the DBD LT group (P = 0.27). Patient survival at 1‐, 3‐, and 5‐years was 92.3%, 86.1%, and 80.3% in the DCD LT group and 92.3%, 85.1%, and 79.5% in the DBD LT group (P = 0.81). IC developed in 11.7% and 2% of patients in the DCD LT group and DBD LT group, respectively (P < 0.001). DCD LT recipients who developed IC had inferior graft survival compared with both the DCD non‐IC group (P < 0.001) and the DBD LT group (P < 0.001); no difference in graft survival was observed between the DCD non‐IC group and the DBD LT group (P = 0.50). Physical and Mental Composite Scores on the SF‐12 QOL questionnaire were similar between the DCD LT and DBD LT groups (44.0 versus 45.4; P = 0.34 and 51.9 versus 52.2; P = 0.83), respectively. Similar longterm survival and QOL scores can be achieved between DCD LT and DBD LT. Prevention of IC in DCD LT yields excellent graft and patient survival with virtually no difference compared with DBD LT. Liver Transplantation 23 342–351 2017 AASLD.

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Shirin Elizabeth Khorsandi, Arthur William Raven Day, Miriam Cortes, Akash Deep, Anil Dhawan, Hector Vilca‐Melendez, Nigel Heaton
    Is size the only determinant of delayed abdominal closure in pediatric liver transplant?
    The aim was to determine the factors associated with the use of delayed abdominal closure in pediatric liver transplantation (LT) and whether this affected outcome. From a prospectively maintained database, transplants performed in children (≤18 years) were identified (October 2010 to March 2015). Primary abdominal closure was defined as mass closure performed at time of transplant. Delayed abdominal closure was defined as mass closure not initially performed at the same time as transplant; 230 children underwent LT. Of these, 176 (76.5%) had primary closure. Age was similar between the primary and delayed groups (5.0 ± 4.9 versus 3.9 ± 5.0 years; P = 0.13). There was no difference in the graft‐to‐recipient weight ratio (GRWR) in the primary and delayed groups (3.4 ± 2.8 versus 4.1 ± 2.1; P = 0.12). Children with acute liver failure (ALF) were more likely to experience delayed closure then those with chronic liver disease (CLD; P < 0.001). GRWR was similar between the ALF and CLD (3.4 ± 2.4 versus 3.6 ± 2.7; P = 0.68). Primary closure children had a shorter hospital stay (P < 0.001), spent fewer days in pediatric intensive care unit (PICU; P = 0.001), and required a shorter duration of ventilation (P < 0.001). Vascular complications (arterial and venous) were similar (primary 8.2% versus delayed 5.6%; P = 0.52). Graft (P = 0.42) and child survival (P = 0.65) in the primary and delayed groups were similar. Considering timing of mass closure after transplant, patients in the early delayed closure group (<6 weeks) were found to experience a shorter time of ventilation (P = 0.03) and in PICU (P = 0.003). In conclusion, ALF was the main determinant of delayed abdominal closure rather than GRWR. The optimal time for delayed closure is within 6 weeks. The use of delayed abdominal closure does not adversely affect graft/child survival. Liver Transplantation 23 352–360 2017 AASLD.

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Arpita Parmar, Shannon Marie Vandriel, Vicky Lee Ng
    Health‐related quality of life after pediatric liver transplantation: A systematic review
    With improved survival rates after pediatric liver transplantation (LT), attention is targeting improving the health‐related quality of life (HRQOL) as an outcome metric. We conducted a systematic review of the literature to examine HRQOL after pediatric LT, focusing on assessment tools and factors associated with HRQOL. A literature search was conducted through PubMed, Web of Science, Ovid, and Google Scholar for all studies matching the eligibility criteria between January 2004 and September 2016. Titles and abstracts were screened independently by 2 authors and consensus for included studies was achieved through discussion. A total of 25 (2 longitudinal, 23 cross‐sectional) studies were reviewed. HRQOL in pediatric LT recipients is lower than healthy controls, but it is comparable to children with chronic diseases or other pediatric solid organ transplant recipients. Domain scores were lowest in school functioning on the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale 4.0 and general health perception on the Child Health Questionnaire, the 2 most commonly used generic HRQOL instruments. Identified predictors of poor HRQOL include sleep disturbances, medication adherence, and older age at transplantation. Two recently validated disease‐specific HRQOL tools, Pediatric Liver Transplant Quality of Life tool and the Pediatric Quality of Life Inventory 3.0 Transplant Module, have enabled enhanced representation of patient HRQOL, when used in conjugation with generic tools. Heterogeneity in study design and instruments prevented a quantitative, meta‐analysis of the data. In conclusion, continued optimization of durable outcomes for this population mandates prioritization of research focusing on the gap of targeted intervention studies aimed at specific HRQOL subdomains and longitudinal studies to predict the trajectory of HRQOL over time. Liver Transplantation 23 361–374 2017 AASLD.

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Paul D. Morris, Jerome M. Laurence, David Yeo, Michael Crawford, Simone I. Strasser, Geoffrey W. McCaughan, Charbel Sandroussi
    Can response to locoregional therapy help predict longterm survival after liver transplantation for hepatocellular carcinoma? A systematic review
    For a selected group of patients with hepatocellular carcinoma (HCC), liver transplantation (LT) represents the best chance of a cure. Organ shortages necessitate an efficient allocation of resources and careful prioritization on the transplantation waiting list. In this review, we aim to collate and evaluate the published evidence for using response to locoregional therapies (LRTs), measured by modified Response Evaluation Criteria in Solid Tumors (mRECIST), as a predictor of longterm survival after LT. Our aim was to assess whether response to LRTs before LT for HCC, as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria, can help predict recurrence‐free and/or longterm survival outcomes. We searched MEDLINE, Embase, and the Cochrane database. We included randomized controlled trials (RCTs), cohort, case control, and case series studies. Poster and conference abstracts were included. Studies were required to use RECIST or mRECIST criteria when assessing tumor response and were limited to LT for HCC only. A total of 15 records were included in the final systematic review: 7 published manuscripts and 8 conference abstracts. No RCTs were identified. Several included articles were conference abstracts with limited data available. No RCTs were found, and no meta‐analysis was undertaken. Several retrospective cohort studies were identified that demonstrated statistically significant differences in survival and recurrence between different RECIST criteria after LT. Liver Transplantation 23 375–385 2017 AASLD.

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Brian J. Hogan, Enoka Gonsalkorala, Michael A. Heneghan
    Evaluation of coronary artery disease in potential liver transplant recipients
    Improvements in the management of patients undergoing liver transplantation (LT) have resulted in a significant increase in survival in recent years. Cardiac disease is now the leading cause of early mortality, and the stress of major surgery, hemodynamic shifts, and the possibilities of hemorrhage or reperfusion syndrome require the recipient to have good baseline cardiac function. The prevalence of coronary artery disease (CAD) is increasing in LT candidates, especially in those with nonalcoholic fatty liver disease. In assessing LT recipients, we suggest a management paradigm of “quadruple assessment” to include (1) history, examination, and electrocardiogram; (2) transthoracic echocardiogram; (3) functional testing; and (4) where appropriate, direct assessment of CAD. The added value of functional testing, such as cardiopulmonary exercise testing, has been shown to be able to predict posttransplant complications independently of the presence of CV disease. This approach gives the assessment team the greatest chance of detecting and preventing complications related to CAD. Liver Transplantation 23 386–395 2017 AASLD.

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Nicolas M. Intagliata, Hillary Maitland, Shawn Pellitier, Stephen H. Caldwell
    Reversal of direct oral anticoagulants for liver transplantation in cirrhosis: A step forward

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Naoki Yoshida, Takeshi Takamoto, Takuya Hashimoto, Yoshikazu Maruyama, Hayato Abe, Kei Shimada, Tadatoshi Takayama, Masatoshi Makuuchi
    Living donor liver transplantation using an extended right lateral sector graft

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Sharat Varma, Etienne M. Sokal
    Late graft hepatitis and fibrosis in pediatric liver allograft recipients: Current concepts and future developments

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Deirdre Kelly, Steffen Hartleif, Henkjan J. Verkade, Jeremy Rajanayagam, Patrick McKiernan, George Mazariegos, Stefan Hübscher

    Date de mise en ligne : Vendredi 10 fvrier 2017
    Joris J. Blok, Hein Putter, Andries E. Braat
    Scorecard and insights from approaches to liver allocation around the world

    Date de mise en ligne : Vendredi 24 fvrier 2017
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