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Liver transplant tolerance

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https://www.readbyqxmd.com/read/29226102/timing-of-hepatitis-c-virus-treatment-in-liver-transplant-candidates-in-the-era-of-direct-acting-antiviral-agents
#1
REVIEW
George Cholankeril, Mairin Joseph-Talreja, Brandon J Perumpail, Andy Liu, Eric R Yoo, Aijaz Ahmed, Aparna Goel
Chronic hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) in the United States. While most patients with chronic HCV infection remain asymptomatic, up to one-third develop progressive liver disease resulting in cirrhosis. LT is often the only curative treatment once significant hepatic decompensation develops. However, antiviral therapy for HCV infection has advanced markedly in the past 5 years with the discovery and approval of direct-acting antiviral agents. These new regimens are well tolerated, of short duration and highly effective, unlike the traditional treatment with pegylated-interferon and ribavirin...
December 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/29201790/therapy-targeting-stem-cell-in-patients-with-decompensated-cirrhosis-of-liver-in-a-tertiary-treatment-care-center-of-bangladesh
#2
Mamun Al Mahtab, Sheikh Mn Alam, Ahmed L Moben, Ruksana Raihan, Mohammad A Alam, Mohammad A Rahim, Mohammad H Uddin, Sheikh Mohammad Fazle Akbar
Introduction: Decompensated cirrhosis is associated with significantly high mortality resulting from hepatic failure, and liver transplantation seems to be the only viable indication for its management. The objective of this study is to assess if granulocyte colony-stimulating factor (G-CSF), a stimulatory of stem cell in vivo, may be of any benefit for patients with decompensated cirrhosis of liver. Materials and methods: Seventeen consecutive patients with decompensated cirrhosis of liver were recruited in this prospective study...
January 2017: Euroasian Journal of Hepato-Gastroenterology
https://www.readbyqxmd.com/read/29197145/long-term-follow-up-of-ribavirin-free-daa-based-treatment-in-hcv-recurrence-after-orthotopic-liver-transplantation
#3
Sandra Beinhardt, Ramona Al-Zoairy, Karin Kozbial, Albert Friedrich Stättermayer, Andreas Maieron, Rudolf Stauber, Michael Strasser, Heinz Zoller, Ivo Graziadei, Susanne Rasoul-Rockenschaub, Michael Trauner, Peter Ferenci, Harald Hofer
BACKGROUND & AIMS: Excellent efficacy and safety-profile of second generation DAA-combinations improved treatment of chronic hepatitis C (HCV) as well as in HCV-recurrence after orthothopic liver transplantation (OLT). The need of ribavirin-addition is under debate as anemia and decreased renal function are prevalent in transplant-cohorts. Aim of this study was thus to assess safety and long-term efficacy of RBV-free DAA-combinations in HCV-recurrent patients after OLT. PATIENTS & METHODS: 62 OLT-recipients (male:50/81%; age:60...
December 2, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29193356/sofosbuvir-plus-daclatasvir-with-or-without-ribavirin-is-safe-and-effective-for-post-transplant-hepatitis-c-recurrence-and-severe-fibrosis-and-cirrhosis-a-prospective-study
#4
Raffaella Lionetti, Vincenza Calvaruso, Paola Piccolo, Rossella Letizia Mancusi, Chiara Mazzarelli, Stefano Fagiuoli, Marzia Montalbano, Ilaria Lenci, Paola Carrai, Giovanni Guaraldi, Ubaldo Visco-Comandini, Martina Milana, Marco Biolato, Laura Loiacono, Giovanna Valente, Antonio Craxì, Mario Angelico, Gianpiero D'offizi
BACKGROUND: In 2012 an Italian Named Patient Program began for hepatitis C virus (HCV)-infected liver transplant (LT) recipients with advanced fibrosis, before approval of direct antiviral agents (DAA), to benefit severely ill patients. Aim of this "real-life" study was to assess treatment efficacy and safety with an extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without ribavirin (RBV). METHODS: All HCV LT recipients with severe fibrosis in 15 Italian transplant centers were treated with DCV+SOF±RBV for 24 weeks; sustained virological response was assessed at 12 weeks post-treatment (SVR12)...
November 29, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29184683/selective-internal-radiation-therapy-using-yttrium-90-resin-microspheres-in-patients-with-unresectable-hepatocellular-carcinoma-a-retrospective-study
#5
Parvez S Mantry, Ashwini Mehta, Bahar Madani, Alejandro Mejia, Islam Shahin
Background: Selective internal radiation therapy (SIRT) with yttrium-90 resin (Y-90 resin) microspheres has been used as a locoregional therapy for patients with unresectable hepatocellular carcinoma (HCC). We examined patient and disease characteristics that might affect survival after Y-90 resin, as well as treatment tolerability. Methods: Data from patients with unresectable HCC treated with Y-90 resin at a single institution were reviewed retrospectively. Survival was assessed with Kaplan-Meier curves and log-rank tests...
October 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29175009/treatment-with-mtor-inhibitors-after-liver-transplantation-enables-a-sustained-increase-in-regulatory-t-cells-while-preserving-their-suppressive-capacity
#6
Khaldoun Ghazal, Fabien Stenard, Géraldine Dahlqvist, Clément Barjon, Lynda Aoudjehane, Olivier Scatton, Filomena Conti
BACKGROUND: The mammalian targets of rapamycin (mTOR) inhibitors (sirolimus [SRL] and everolimus [EVR]) are used after transplantation for their immunosuppressive activity. Regulatory T-cells (Tregs) play a crucial role in immune tolerance. mTOR inhibitors appear to preserve Tregs, unlike Tacrolimus (Tac). AIM: The aim of this study was to evaluate the number and function of Tregs in liver transplant recipients before and after conversion from Tac to mTOR inhibitors...
November 22, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/29161056/de-novo-food-allergy-in-pediatric-liver-transplantation-recipients
#7
Ratchaneewan Sinitkul, Wiparat Manuyakorn, Wasu Kamchaisatian, Soamarat Vilaiyuk, Suwat Benjaponpitak, Chatmanee Lertudompholwanit, Suporn Treepongkaruna
BACKGROUND: Food allergy (FA) prevalence is increasing in pediatric liver transplantation (LT). However, the clinical course is still limited. OBJECTIVE: This retrospective cohort study aimed to identify the prevalence, risk factors, and the natural history of de novo FA in children post LT. METHODS: Medical records of pediatric LT recipients from Jan 2001 - Dec 2014 were reviewed. De novo FA was diagnosed by symptoms after exposure to culprit food occurring after LT, and improvement after diet elimination...
November 22, 2017: Asian Pacific Journal of Allergy and Immunology
https://www.readbyqxmd.com/read/29139181/direct-antiviral-treatment-of-chronic-hepatitis-c-in-heart-transplant-recipients
#8
Martina Vitrone, Roberto Andini, Irene Mattucci, Ciro Maiello, Luigi Atripaldi, Emanuele Durante-Mangoni, Rosa Zampino
Direct-acting antiviral agents (DAAs) are a safe and effective treatment for chronic hepatitis C (CHC). This may be particularly valuable for patients with severe comorbidities or baseline conditions, including non-liver solid organ transplant. We report cases of two heart transplant recipients with CHC treated with DAA (sofosbuvir and daclatasvir) achieving sustained virological response. Treatment was well tolerated and no relevant side effects were observed. The drug-drug interactions and graft function were carefully monitored...
November 15, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29135830/tissue-resident-lymphocytes-in-solid-organ-transplantation-innocent-passengers-or-the-key-to-organ-transplant-survival
#9
Amy C Prosser, Axel Kallies, Michaela Lucas
Short-term outcomes of solid organ transplantation have improved dramatically over the past several decades; however, long-term survival has remained static over the same time period, and chronic rejection remains a major cause of graft failure. The importance of donor, or 'passenger', lymphocytes to the induction of tolerance to allografts was recognized in the 1990s; however, their precise contribution to graft acceptance or rejection has not been elucidated. Recently, specialized populations of tissue-resident lymphocytes in nonlymphoid organs have been described...
November 14, 2017: Transplantation
https://www.readbyqxmd.com/read/29125261/hepatitis-b-and-liver-transplantation
#10
Alberto Ferrarese, Alberto Zanetto, Francesco P Russo
Liver transplantation (LT) is the only effective treatment for hepatitis B-virus (HBV) related end stage liver disease, even if the outcome of these patients, has significantly improved after introduction of effective and well tolerated nucleos/tide analogues (NUC). Pre-transplant therapy has been initially based on lamivudine, but entecavir and tenofovir represent the currently recommended first-line therapeutic option in patients with HBV decompensated cirrhosis. After LT, the development of hepatitis B immunoglobulin (HBIG) in the early 1990s change dramatically the prognosis of these patients by reducing the incidence of HBV recurrence and increasing survival rate...
November 10, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/29121675/astaxanthin-prevents-ischemia-reperfusion-injury-of-the-steatotic-liver-in-mice
#11
Shaowei Li, Terumi Takahara, Masayuki Fujino, Yasuyuki Fukuhara, Toshiro Sugiyama, Xiao-Kang Li, Shiro Takahara
Steatosis has a low tolerance against ischemia-reperfusion injury (IRI). To prevent IRI in the steatotic liver, we attempted to elucidate the protective effect of astaxanthin (ASTX) in the steatotic liver model by giving mice a methionine and choline-deficient high fat (MCDHF) diet. Levels of lipid peroxidation and apoptosis, the expression of inflammatory cytokines and heme oxygenase (HO)-1, in the liver were assessed. Reactive oxygen species (ROS), inflammatory cytokines, apoptosis-related proteins and members of the signaling pathway were also examined in isolated Kupffer cells and/or hepatocytes from the steatotic liver...
2017: PloS One
https://www.readbyqxmd.com/read/29113427/-clinical-application-of-mesenchymal-stem-cells-in-treatment-of-acute-on-chronic-liver-failure-and-related-research-advances
#12
L Y Feng, D Z Zhang
Acute-on-chronic liver failure is a syndrome characterized by acute exacerbation of chronic hepatitis, organ failure, and high mortality. Clinical treatment of acute-on-chronic liver failure included comprehensive medical treatment, artificial liver support system, and liver transplantation, but such methods have their own shortcomings and patients tend to have a poor prognosis. Mesenchymal stem cells (MSCs), as a new type of cell therapy, have wide sources and are easy to extract and culture. Many studies have shown that MSC treatment not only helps to achieve a high survival rate, but also has good tolerability and safety; therefore, the clinical value of MSCs has become a hot research topic...
September 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29111569/the-influence-of-immunosuppressants-on-direct-acting-antiviral-therapy-is-dependent-on-hepatitis-c-virus-genotype
#13
Alexandra Frey, Katja Piras-Straub, Andreas Walker, Jörg Timm, Guido Gerken, Kerstin Herzer
BACKGROUND: Direct-acting antivirals (DAA) have substantially increased sustained virological response rates after liver transplantation, with improved tolerance compared to interferon-based therapy. The influence of immunosuppressive agents on the efficacy of DAAs has not been clarified. METHODS: Subgenomic HCV replicons for genotype (GT) 1b, 2b, 3a and 4a were treated with the mammalian target of rapamycin (mTOR) inhibitors everolimus and sirolimus or with the calcineurin inhibitors (CNI) cyclosporine or tacrolimus, either alone or in combination with selected DAAs...
November 7, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29107679/efficacy-and-safety-of-selective-internal-radiotherapy-with-yttrium-90-resin-microspheres-compared-with-sorafenib-in-locally-advanced-and-inoperable-hepatocellular-carcinoma-sarah-an-open-label-randomised-controlled-phase-3-trial
#14
Valérie Vilgrain, Helena Pereira, Eric Assenat, Boris Guiu, Alina Diana Ilonca, Georges-Philippe Pageaux, Annie Sibert, Mohamed Bouattour, Rachida Lebtahi, Wassim Allaham, Hélène Barraud, Valérie Laurent, Elodie Mathias, Jean-Pierre Bronowicki, Jean-Pierre Tasu, Rémy Perdrisot, Christine Silvain, René Gerolami, Olivier Mundler, Jean-Francois Seitz, Vincent Vidal, Christophe Aubé, Frédéric Oberti, Olivier Couturier, Isabelle Brenot-Rossi, Jean-Luc Raoul, Anthony Sarran, Charlotte Costentin, Emmanuel Itti, Alain Luciani, René Adam, Maïté Lewin, Didier Samuel, Maxime Ronot, Aurelia Dinut, Laurent Castera, Gilles Chatellier
BACKGROUND: Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 ((90)Y) resin microspheres in patients with hepatocellular carcinoma. METHODS: SARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation...
October 26, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29104778/change-in-the-content-of-immunoproteasomes-and-macrophages-in-rat-liver-at-the-induction-of-donor-specific-tolerance
#15
Ya D Karpova, V D Ustichenko, N M Alabedal'karim, A A Stepanova, Yu V Lyupina, K I Boguslavski, G A Bozhok, N P Sharova
Induction of donor specific tolerance (DST) by the introduction of donor cells into a recipient's portal vein is one of the approaches used to solve the problem of transplant engraftment. However, the mechanism of DST development remains unclear to this moment. In the present work, we first studied the change in the content of immunoproteasomes and macrophages of the liver at early stages of the development of allospecific portal tolerance in rats by Western blotting and flow cytofluorimetry. On the basis of the data obtained, we can conclude that the induction of DST is an active process characterized by two phases during which the level of the proteasome immune subunits LMP2 and LMP7 in liver mononuclear cells, including Kupffer cells, and the number of Kupffer cells change...
July 2017: Acta Naturae
https://www.readbyqxmd.com/read/29100944/regulatory-dendritic-cells-for-promotion-of-liver-transplant-operational-tolerance-rationale-for-a-clinical-trial-and-accompanying-mechanistic-studies
#16
REVIEW
Angus W Thomson, Abhinav Humar, Fadi G Lakkis, Diana M Metes
Dendritic cells (DC) are rare, bone marrow (BM)-derived innate immune cells that critically maintain self-tolerance in the healthy steady-state. Regulatory DC (DCreg) with capacity to suppress allograft rejection and promote transplant tolerance in pre-clinical models can readily be generated from BM precursors or circulating blood monocytes. These DCreg enhance allograft survival via various mechanisms, including promotion of regulatory T cells. In non-human primates receiving minimal immunosuppressive drug therapy (IS), infusion of DCreg of donor origin, one week before transplant, safely prolongs renal allograft survival and selectively attenuates anti-donor CD8(+) memory T cell responses in the early post-transplant period...
October 31, 2017: Human Immunology
https://www.readbyqxmd.com/read/29100619/indoxyl-3-sulfate-inhibits-maturation-and-activation-of-human-monocyte-derived-dendritic-cells
#17
Sakhila Ghimire, Carina Matos, Massimiliano Caioni, Daniela Weber, Katrin Peter, Ernst Holler, Marina Kreutz, Kathrin Renner
Indole is produced from l-tryptophan by commensal bacteria and further metabolized to indoxyl 3-sulfate (I3S) in the liver. Physiologic concentrations of I3S are related to a lower risk to develop graft versus host disease in allogeneic stem cell transplanted patients pointing towards an immunoregulatory function of I3S. Here we investigated the impact of I3S on the maturation of human monocyte-derived dendritic cells (DCs). Even pathophysiologic concentrations of I3S did not affect viability of mature DCs, but I3S decreased the expression of co-stimulatory molecules such as CD80 and CD86 on mature DCs...
October 6, 2017: Immunobiology
https://www.readbyqxmd.com/read/29097869/delayed-and-short-course-of-rapamycin-prevents-organ-rejection-after-allogeneic-liver-transplantation-in-rats
#18
Salim Hamdani, Allan Thiolat, Sina Naserian, Cynthia Grondin, Stéphane Moutereau, Anne Hulin, Julien Calderaro, Philippe Grimbert, José Laurent Cohen, Daniel Azoulay, Caroline Pilon
AIM: To test whether a delayed and short course of rapamycin would induce immunosuppressive effects following allogeneic orthotopic liver transplantation (OLT) in rats. METHODS: Allogeneic OLTs were performed using Dark Agouti livers transplanted into Lewis recipients, and syngeneic OLTs were performed using the Lewis rat strain. Rapamycin (1 mg/kg per day) was administered by gavage from day 4 to day 11 post-transplantation. Lymphocyte cellular compartments were analyzed by flow cytometry in draining lymph nodes, non-draining lymph nodes and the spleen at days 11 and 42 in rapamycin-treated rats, untreated control rats and syngeneic grafted rats...
October 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29057387/toward-solving-the-etiological-mystery-of-primary-biliary-cholangitis
#19
Atsushi Tanakaa, Patrick Sc Leung, Howard A Young, M Eric Gershwin
Primary biliary cholangitis (PBC) is considered a model autoimmune disease due to its signature AMA autoantibody, female predominance and relatively specific portal infiltration and cholestasis. The identification and cloning of the major mitochondrial autoantigens, recognized by AMA, have served as an immunologic platform to identify the earliest events involved in loss of tolerance. Despite the relative high concordance rate in identical twins, genome wide association studies have not proven clinically useful and have led to suggestions of epigenetic events...
June 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29054397/tolerance-in-clinical-liver-transplantation
#20
REVIEW
Josh Levitsky, Sandy Feng
While advances in immunosuppressive therapy have lowered the rate of acute rejection following liver transplantation, the consequence has been an increase in morbidity and mortality related to the lifelong need for maintenance immunosuppression. These complications include an increased risk of malignancy, infection, metabolic disorders, and chronic kidney disease, as well as high health care costs associated with these therapies and the required drug monitoring. Given these issues, most clinicians attempt trial and error dose minimization with variable success rates, and there has been significant interest in full drug withdrawal in select patients through research protocols...
October 17, 2017: Human Immunology
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