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Liver transplant tolerance

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https://www.readbyqxmd.com/read/28790832/combination-of-sofosbuvir-and-daclatasvir-in-the-treatment-of-genotype-3-chronic-hepatitis-c-virus-infection-in-patients-on-maintenance-hemodialysis
#1
Jan Sperl, Sona Frankova, Miluse Kreidlova, Dusan Merta, Monika Tothova, Julius Spicak
Chronic hepatitis C virus infection (HCV) has a negative impact on the long-term survival of recipients of kidney transplants. HCV should be treated in hemodialyzed patients before their enlistment for kidney transplantation in order to avoid the reactivation of virus after transplantation. Direct-acting antivirals represent the current standard of care in hemodialyzed patients with HCV genotypes 1 and 4; in patients with genotypes 2 or 3, the optimal regimen is yet to be established. Sofosbuvir (SOF) and daclatasvir (DCV) represent an antiviral pangenotypic regimen with favorable pharmacokinetics in hemodialyzed patients...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28782153/n-acetylcysteine-and-prednisolone-treatment-improved-serum-biochemistries-in-suspected-flupirtine-cases-of-severe-idiosyncratic-liver-injury
#2
Jürgen Borlak, Florian van Bömmel, Thomas Berg
BACKGROUND & AIMS: The analgesic flupirtine has been linked to cases of severe idiosyncratic drug-induced liver injury (sFILI). We therefore examined whether N-acetylcysteine (NAC) and glucocorticoid therapy is effective in the management of sFILI. METHODS: In a retrospective cohort study efficacy of NAC-infusion and oral prednisolone treatments on liver-function-tests (LFTs) and clinical outcome of 21 sFILI cases was evaluated by comparing it to an external cohort of 30 sFILI cases not receiving the antidote...
August 7, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28752938/dendritic-cells-in-hepatitis-and-liver-transplantation
#3
Radika Soysa, Xia Wu, I Nicholas Crispe
Dendritic cells (DCs) play a key role in innate immune responses, and are also the most effective cells for the activation of T cell immunity. They acquire antigen and process it, then display in on the cell surface bound in a non-covalent complex with HLA molecules of class I (HLA-A, B, C) and class II (HLA-DR). These cells are subdivided into three main subsets, two called myeloid or classical DCs of types 1 and 2, and one called plasmacytoid. The myeloid DCs process and present antigen, while the plasmacytoid DCs also strongly respond to viral signals by secreting Type 1 Interferon...
July 28, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28751632/extracorporeal-membrane-oxygenation-support-for-rituximab-induced-acute-respiratory-distress-syndrome-in-an-abo-incompatible-living-donor-liver-transplant-recipient-successful-management-of-a-rare-complication-and-a-review-of-the-literature
#4
Ping-Chun Li, Ashok Thorat, Shih-Chao Hsu, Kin-Shing Poon, Horng-Ren Yang, Te-Hung Chen, Chun-Chieh Yeh, Long-Bin Jeng
BACKGROUND Rituximab is commonly used to reduce the agglutinin titer in ABO-incompatible liver transplant recipients. Although well-tolerated, rituximab infusion therapy may result in severe pulmonary adverse effects such as drug-induced pneumonitis, leading to acute respiratory distress syndrome (ARDS), which has a high mortality rate. Management of such rare cases in an ABO-incompatible patient has never been described before. Herein, we present successful use of extracorporeal membrane oxygenation (ECMO) support for rituximab-induced ARDS in an ABO-incompatible living donor liver transplantation (LDLT) recipient...
July 28, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28740511/safety-and-tolerance-of-donor-derived-mesenchymal-stem-cells-in-pediatric-living-donor-liver-transplantation-the-mystep1-study
#5
Steffen Hartleif, Michael Schumm, Michaela Döring, Markus Mezger, Peter Lang, Marc H Dahlke, Joachim Riethmüller, Alfred Königsrainer, Rupert Handgretinger, Silvio Nadalin, Ekkehard Sturm
BACKGROUND: Calcineurin inhibitors (CNI) have significantly improved patient and graft survival in pediatric liver transplantation (pLT). However, CNI toxicity leads to significant morbidity. Moreover, CNIs cannot prevent long-term allograft injury. Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties, which may promote allograft tolerance and ameliorate toxicity of high-dose CNI. The MYSTEP1 trial aims to investigate safety and feasibility of donor-derived MSCs in pLT...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28736013/outcomes-of-highly-sensitized-patients-undergoing-simultaneous-liver-and-kidney-transplantation-a-single-center-experience-with-desensitization
#6
J A Steggerda, A Kang, S-H Pan, V Sundaram, N N Nissen, A S Klein, T Todo, A Annamalai, A Vo, S C Jordan, I K Kim
BACKGROUND: Preformed donor-specific human leukocyte antigen antibodies (DSAs) in patients undergoing simultaneous liver and kidney transplantation (SLKT) are an independent risk factor for poorer patient and renal allograft survival. The outcomes of patients highly sensitized (HS) against HLA antigens undergoing SLKT and select HS SLKT recipients undergoing desensitization at a high-volume desensitization center were investigated. METHODS: Seventy-five patients undergoing SLKT at a high-volume desensitization center between January 1, 2001, and December 31, 2015, were retrospectively reviewed...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28722153/pharmacokinetics-and-safety-of-the-anti-human-cytomegalovirus-drug-letermovir-in-subjects-with-hepatic-impairment
#7
D Kropeit, D McCormick, K Erb-Zohar, V S Moiseev, Z D Kobalava, H P Stobernack, H Zimmermann, H Rübsamen-Schaeff
AIM: Human cytomegalovirus constitutes a prevalent and serious threat to immunocompromised individuals and requires new treatments. Letermovir is a novel viral-terminase inhibitor that has demonstrated prophylactic/preemptive activity against human cytomegalovirus in Phase 2 and 3 transplant trials. As unchanged letermovir is primarily excreted via the liver by bile, this trial aimed to assess the effect of hepatic impairment on letermovir pharmacokinetics. METHODS: Phase 1, open-label, parallel-group pharmacokinetic and safety comparison of multiple once-daily oral letermovir in female subjects with hepatic impairment and healthy matched controls...
July 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28687016/safety-and-tolerability-of-deferasirox-in-pediatric-hematopoietic-stem-cell-transplant-recipients-one-facility-s-five-years-experience-of-chelation-treatment
#8
Natalia Maximova, Massimo Gregori, Roberto Simeone, Aurelio Sonzogni, Giulia Boz, Carmen Fucile, Valeria Marini, Antonietta Martelli, Francesca Mattioli
42 pediatric patients with iron overload, who underwent liver biopsy and DFX treatment after hematopoietic stem cell transplantation were included in the study group. The patients were divided into two groups diversified according to deferasirox trough plasma concentrations (DFX Ctrough) with cut-off equal to10 mcg/mL. The average dose of DFX was 25.9 mg/kg in the DFX Ctrough < 10 mcg/mL group versus 19.2 mg/kg in the DFX Ctrough > 10 mcg/mL group (p=0,0003). The mean duration of DFX treatment was 135...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28673260/gene-expression-variations-in-high-altitude-adaptation-a-case-study-of-the-asiatic-toad-bufo-gargarizans
#9
Weizhao Yang, Yin Qi, Bin Lu, Liang Qiao, Yayong Wu, Jinzhong Fu
BACKGROUND: Genome-wide investigation of molecular mechanisms for high-altitude adaptation has attracted great attention in the last few years. In order to understand the contribution of gene expression level variations to high-altitude adaptation in Asiatic toads (Bufo gargarizans), we implemented a reciprocal transplant experiment between low- and high-altitude sites and sequenced 12 transcriptomes from brain, heart, and liver tissues. RESULTS: A large number of genes with expression differences (DEGs) between high- and low-altitude individuals (193 fixed and 844 plastic) were identified, and the majority of them were tissue specific...
July 3, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28660147/effectiveness-of-ledipasvir-sofosbuvir-with-without-ribavarin-in-liver-transplant-recipients-with-hepatitis-c
#10
Sammy Saab, Justin Rheem, Melissa A Jimenez, Tiffany M Fong, Michelle H Mai, Caterina A Kachadoorian, Negin L Esmailzadeh, Sherona N Bau, Susan Kang, Samantha D Ramirez, Jonathan Grotts, Gina Choi, Francisco A Durazo, Mohammed M El-Kabany, Steven-Huy B Han, Ronald W Busuttil
Background and Aims: Recurrent infection of hepatitis C virus (HCV) in liver transplant (LT) recipients is universal and associated with significant morbidity and mortality. Methods: We retrospectively evaluated the safety and efficacy of ledipasvir/sofosbuvir with and without ribavirin in LT recipients with recurrent genotype 1 hepatitis C. Results: Eighty-five LT recipients were treated for recurrent HCV with ledipasvir/sofosbuvirwith and without ribavirin for 12 or 24 weeks. The mean (± standard deviation [SD]) time from LT to treatment initiation was 68 (±71) months...
June 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28638096/identification-of-a-flavonoid-isolated-from-plum-prunus-domestica-as-a-potent-inhibitor-of-hepatitis-c-virus-entry
#11
Mihika Bose, Mohini Kamra, Ranajoy Mullick, Santanu Bhattacharya, Saumitra Das, Anjali A Karande
Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases that often requires liver transplantation. The standard therapies are limited by severe side effects, resistance development, high expense and in a substantial proportion of cases, fail to clear the infection which bespeak the need for development of well-tolerated antivirals. Since most of the drug development strategies target the replication stage of viral lifecycle, the identification of entry inhibitors might be crucial especially in case of liver-transplant recipients...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28608637/regulatory-t-cell-therapy-in-liver-transplantation
#12
REVIEW
Gavin P Whitehouse, Andrew Hope, Alberto Sanchez-Fueyo
Modern immunosuppression drug regimens have produced excellent short-term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants, and therefore, liver transplantation offers an attractive setting in which to study tolerizing therapies...
August 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28606879/can-immunosuppression-be-stopped-after-liver-transplantation
#13
REVIEW
Pierre-Alain Clavien, Xavier Muller, Michelle L de Oliveira, Philipp Dutkowski, Alberto Sanchez-Fueyo
Liver transplantation has improved dramatically over the past three decades, mainly as a result of advances in surgical techniques and management of post-transplant complications. The focus has now turned towards rescuing additional organs in the face of scarce organ supply, or prevention of long-term toxicity associated with immunosuppression. The liver appears to be privileged in terms of immune tolerance, with a low incidence of antibody-mediated rejection, which is in sharp contrast to other solid organ transplants, such as kidney, lung, and heart transplants...
July 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28603052/efficacy-and-safety-of-mycophenolate-mofetil-and-tacrolimus-as-second-line-therapy-for-patients-with-autoimmune-hepatitis
#14
Cumali Efe, Hannes Hagström, Henriette Ytting, Rahima A Bhanji, Niklas F Müller, Qixia Wang, Tugrul Purnak, Luigi Muratori, Mårten Werner, Hanns-Ulrich Marschall, Paolo Muratori, Fulya Gunşar, Daniel Klintman, Albert Parés, Alexandra Heurgué-Berlot, Thomas D Schiano, Mustafa Cengiz, Michele May-Sien Tana, Xiong Ma, Aldo J Montano-Loza, Thomas Berg, Sumita Verma, Fin Stolze Larsen, Ersan Ozaslan, Michael A Heneghan, Eric M Yoshida, Staffan Wahlin
BACKGROUND & AIMS: Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. METHODS: We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo)...
June 8, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28546792/hepatitis-c-virus-and-liver-transplantation
#15
Kalyan Ram Bhamidimarri, Sanjaya K Satapathy, Paul Martin
Hepatitis C virus (HCV) is a major cause of death from infectious disease and is still the leading indication for liver transplantation in the United States and other Western countries. All-oral, direct-acting antiviral (DAA) therapies have revolutionized the field, with HCV cure rates of more than 90% among treated patients. The safety and tolerability of these DAA agents have expanded the feasibility of HCV treatment even in the challenging pre- and post-liver transplant settings. However, the unique properties of DAA agents and the host profiles in these settings can limit the generalizability of HCV regimens, and prolongation of treatment duration or addition of ribavirin may be required in certain scenarios to optimize treatment outcomes...
April 2017: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28535517/coupled-plasma-filtration-adsorption-application-for-liver-and-thyroid-toxins
#16
Gabriele Donati, Irene Capelli, Anna Laura Croci Chiocchini, Nicolò Natali, Anna Scrivo, Gaetano La Manna
Coupled plasma filtration and adsorption (CPFA) is a detoxification system that combines a plasma adsorption circuit and a continuous renal replacement therapy circuit. Its main application is for sepsis and septic shock with or without acute renal failure. Several recent studies have suggested that CPFA can reduce the mortality when the volume of plasma absorbed on the styrenic resin is at least >0.18 L/kg/day. At present, new applications for CPFA are under investigation, also in patients without significant kidney failure...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28518214/immune-monitoring-as-prerequisite-for-transplantation-tolerance-trials
#17
REVIEW
K Behnam Sani, B Sawitzki
Ever since its first application in clinical medicine, scientists have been urged to induce tolerance towards foreign allogeneic transplants and thus avoid rejection by the recipient's immune system. This would circumvent chronic use of immunosuppressive drugs (IS) and thus avoid development of IS-induced side effects, which are contributing to the still unsatisfactory long-term graft and patient survival after solid organ transplantation. Although manifold strategies of tolerance induction have been described in preclinical models, only three therapeutic approaches have been utilized successfully in a still small number of patients...
August 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28503959/emerging-drugs-for-prevention-of-t-cell-mediated-rejection-in-liver-and-kidney-transplantation
#18
REVIEW
Tiffany Cl Wong, Chung-Mau Lo, James Yy Fung
Acute and chronic graft rejection continues to be an important problem after solid organ transplantation. With the introduction of potent immunosuppressive agents such as calcineurin inhibitors, the risk of rejection has been significantly reduced. However, the adverse effects of life-long immunosuppression remain a concern, and there exist a fine balance between over-immunosuppression and risk of rejection. Areas covered: In this review, the current standard of care in immunosuppressive therapy, including the use of steroids, calcineurin inhibitors, mycophenolate prodrugs and mammalian target of rapamycin inhibitors, will be discussed...
June 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28481004/tips-and-pitfalls-in-direct-ligation-of-large-spontaneous-splenorenal-shunt-during-liver-transplantation
#19
Hyeyoung Kim, Kyung Chul Yoon, Kwang-Woong Lee, Nam-Joon Yi, Hae Won Lee, YoungRok Choi, Dongkyu Oh, Hyo-Sin Kim, Suk Kyun Hong, Sung Woo Ahn, Kyung-Suk Suh
Patients with large spontaneous splenorenal shunts (SRSs) prove challenging during liver transplantation (LT), regardless of organizing portal vein (PV) thrombosis. Here, we detail the clinical outcomes of 26 patients who underwent direct ligation of large SRSs during LT. Direct ligation of large SRS was applied in poor portal flow during LT. We performed temporary test clamping of the SRS before direct ligation and applied PV pressure monitoring in patients who showed signs of portal hypertension, such as bowel edema...
July 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28480239/safety-and-efficacy-of-anidulafungin-for-fungal-infection-in-patients-with-liver-dysfunction-or-multiorgan-failure
#20
Anita Verma, Georg Auzinger, Michal Kantecki, James Campling, Dean Spurden, Fran Percival, Nigel Heaton
BACKGROUND: The objective of this study was to review our clinical experience on the safety and efficacy of anidulafungin, an echinocandin antifungal, in the treatment of invasive fungal infections (IFIs) in patients with moderate to severe abnormal liver function tests or multiorgan failure and IFI, in a large United Kingdom Liver Centre. METHODS: The clinical records of the first 50 consecutive patients treated for IFI with anidulafungin between January 7, 2009 and March 2, 2011 were analyzed...
2017: Open Forum Infectious Diseases
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