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liver transplantation immunology

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https://www.readbyqxmd.com/read/28392163/current-progress-in-non-viral-rnai-based-delivery-strategies-to-lymphocytes
#1
REVIEW
Shoshy Mizrahy, Inbal Hazan-Halevy, Niels Dammes, Dalit Landesman-Milo, Dan Peer
RNAi-based therapy holds great promise, as it can be utilized for the treatment of multiple conditions in an accurate manner via sequence-specific manipulation of gene expression. To date, RNAi therapeutics have advanced into clinical trials for liver diseases and solid tumors; however, delivery of RNAi to leukocytes in general and to lymphocytes in particular remains a challenge. Lymphocytes are notoriously hard to transduce with RNAi payloads and are disseminated throughout the body, often located in deep tissues; therefore, developing an efficient systemic delivery system directed to lymphocytes is not a trivial task...
April 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28371374/vitamin-a-deficiency-in-chronic-cholestatic-liver-disease-is-vitamin-a-therapy-beneficial
#2
Cora Freund, Daniel Nils Gotthardt
Chronic cholestatic diseases are progressive diseases of the biliary tract that cause hepatic fibrosis and ultimately lead to liver failure. Liver transplantation is the sole curative option currently available, and because of high morbidity and mortality rates of these diseases, new therapeutic approaches are needed. Vitamin A is a nutrient essential for health as it regulates many processes, including epithelial growth and immunological processes. Vitamin A is primarily stored in hepatic stellate cells, and during liver injury, through an unknown mechanism, these cells lose vitamin A and convert into collagen-producing myofibroblasts, which contributes to hepatic fibrosis...
March 29, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28364817/management-of-immunosuppression-in-liver-transplantation
#3
REVIEW
Renumathy Dhanasekaran
Liver transplantation outcomes have significantly improved over the past few decades owing largely to the introduction of effective immunosuppression medications. Further comprehension of the unique immune microenvironment of the liver has led to the development of newer molecular targeted therapeutics. Understanding the mechanism of action and adverse effect profiles of these medications is crucial for appropriate management of posttransplant patients. In this review, the author describes the immunologic response elicited by liver transplantation, chronicles the various immunosuppressant drug classes, discusses the evidence behind their use, and evaluates the management of special subpopulations of posttransplantation patients...
May 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/28353041/the-inhibitory-effect-of-mesenchymal-stem-cells-with-rad-nk4-on-liver-cancer
#4
Chao Cai, Lingling Hou, Jingsi Zhang, Diandian Zhao, Ziling Wang, Honggang Hu, Jinsheng He, Weijun Guan, Yuehui Ma
Mesenchymal stem cells (MSCs) can migrate to the tumor site and integrate into the tumor tissue. As a delivery vehicle of antitumor factors, MSCs have been tried in various tumor therapies. NK4 can both inhibit the growth, metastasis, and invasion of tumor cells induced by hepatocyte growth factor (HGF) and suppress tumor angiogenesis that is independent on HGF/cellular-mesenchymal-to-transition factor pathway. Adenovirus can directly deliver NK4 for tumor treatment but may induce immunological rejection. We combined MSCs with an adenovirus vector to deliver NK4 for liver tumor treatment...
March 28, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28321910/the-coming-of-age-of-a-young-subspecialty-paediatric-hepatology
#5
REVIEW
Antal Németh
Paediatric hepatology dates from the 1970s and it is the youngest of the organ-specific subspecialties. Since then there have been impressive achievements in the fields of anatomical, metabolic, immunological and neoplastic diseases and the advent of modern molecular biology has resulted in a marked increase in exact diagnoses. Liver transplants provided enormous stimulus for the discipline. Due to changing morbidity patterns the discipline faces new challenges, such as environmental and lifestyle induced liver diseases, but different forms of chronic viral hepatitis are diminishing...
March 21, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/28320105/anti-fibrotic-potential-of-human-umbilical-cord-mononuclear-cells-and-mouse-bone-marrow-cells-in-ccl4-induced-liver-fibrosis-in-mice
#6
Nageh Ahmed Elmahdy, Samia Salem Sokar, Mohamed Labib Salem, Naglaa Ibrahim Sarhan, Sherin Hamed Abou-Elela
Liver fibrosis is the consequence of hepatocyte injury that leads to the activation of hepatic stellate cells (HSC). The treatment of choice is Liver transplantation; however, it has many problems such as surgery-related complications, immunological rejection and high costs associated with the procedure. Stem cell-based therapy would be a potential alternative, so the aim of this study is to investigate the therapeutic potential of human umbilical cord mononuclear cells (MNC) and mouse bone marrow cells (BMC) against carbon tetrachloride (CCl4) induced liver fibrosis in mice and compare it with that of silymarin...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28314211/the-role-of-kupffer-cells-in-hepatic-diseases
#7
REVIEW
Peizhi Li, Kun He, Jinzheng Li, Zuojin Liu, Jianping Gong
Kupffer cells (KCs) constitute 80-90% of the tissue macrophages present in the body. Essential to innate and adaptive immunity, KCs are responsible for the swift containment and clearance of exogenous particulates and immunoreactive materials which are perceived as foreign and harmful to the body. Similar to other macrophages, KCs also sense endogenous molecular signals that may result from perturbed homeostasis of the host. KCs have been implicated in host defense and the pathogenesis of various hepatic diseases, including endotoxin tolerance, liver transplantation, nonalcoholic fatty liver disease, and alcoholic liver disease...
March 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28240817/liver-ex-vivo-machine-perfusion-preservation-a-review-of-the-methodology-and-results-of-large-animal-studies-and-clinical-trials
#8
REVIEW
Hazel Marecki, Adel Bozorgzadeh, Robert Porte, Henri Leuvenink, Korkut Uygun, Paulo Martins
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...
February 27, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28240807/genetic-hematological-and-immunological-disorders-transmissible-with-liver-transplantation
#9
REVIEW
Amy Tan, Sander S Florman, Thomas D Schiano
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...
February 27, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28214926/role-of-serum-level-and-genetic-variation-of-il-28b-in-interferon-responsiveness-and-advanced-liver-disease-in-chronic-hepatitis-c-patients
#10
Abdolvahab Alborzi, Tayebeh Hashempour, Javad Moayedi, Zahra Musavi, Gholamreza Pouladfar, Shahin Merat
Interleukin-28B (IL-28B) is suspected to be associated with response to treatment and one of the basic immunological backgrounds in liver transplant candidate (LTC). We aimed to assess whether genotypes of IL-28B can play a role in therapeutic response or advanced stages of liver disease. A total of 364 subjects were genotyped for IL-28B rs12979860 and rs8099917 SNPs using PCR-RFLP assay. Moreover, IL-28 serum level, HCV loads, and genotype were performed. A significant increase was observed in the frequencies of unfavorable rs12979860 genotypes/CT + TT in the chronic hepatitis C (CHC) and LTC groups...
April 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28164136/the-role-of-humoral-alloreactivity-in-liver-transplantation-lessons-learned-and-new-perspectives
#11
REVIEW
Elaine Y Cheng
More than ten years after the initial description of the humoral theory of transplantation by Dr. Paul I. Terasaki, the significance of humoral alloimmunity in liver transplantation has yet to be clearly defined. The liver allograft has an inherent tolerogenic capacity which confers its resistance to cell-mediated as well as antibody-mediated rejection. Nevertheless, the protection against alloimmunity is not complete, and antibody-mediated tissue injury can occur in the liver graft under specific circumstances...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28131494/immunomodulation-by-hyperimmunoglobulins-after-solid-organ-transplantation-beyond-prevention-of-viral-infection
#12
REVIEW
Rogier van Gent, Herold J Metselaar, Jaap Kwekkeboom
Hyperimmunoglobulins are pharmaceutical formulations of human IgG which contain high titers of antibodies against specific viruses. They have been successfully used in solid organ transplantation (SOT) to prevent Cytomegalovirus (CMV) and Hepatitis B Virus (HBV) infection. The introduction of effective and cheaper antiviral drugs has resulted in decreasing usage of hyperimmunoglobulins in SOT. However, it may still be attractive to combine antiviral drug therapy with hyperimmunoglobulins after SOT, as there is some evidence that hyperimmunoglobulins, similar to high doses of intravenous immunoglobulins (IVIgs), might exert anti-inflammatory activity and thereby prevent immunological graft damage and improve graft and patient survival...
January 19, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28120462/research-priority-setting-in-organ-transplantation-a-systematic-review
#13
Allison Tong, Benedicte Sautenet, Jeremy R Chapman, Claudia Harper, Peter MacDonald, Nicholas Shackel, Sally Crowe, Camilla Hanson, Sophie Hill, Anneliese Synnot, Jonathan C Craig
Barriers to access and long-term complications remain a challenge in transplantation. Further advancements may be achieved through research priority setting with patient engagement to strengthen its relevance. We evaluated research priority setting in solid organ transplantation and described stakeholder priorities. Databases were searched to October 2016. We synthesized the findings descriptively. The 28 studies (n = 2071 participants) addressed kidney [9 (32%)], heart [7 (25%)], liver [3 (11%)], lung [1 (4%)], pancreas [1 (4%)], and nonspecified organ transplantation [7 (25%)] using consensus conferences, expert panel meetings, workshops, surveys, focus groups, interviews, and the Delphi technique...
January 25, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28104168/meld-and-child-pugh-scores-are-related-to-immune-status-of-intrahepatic-natural-killer-cells-in-liver-transplant-candidates
#14
N Tanimine, Y Tanaka, T Abe, J Piao, K Ishiyama, T Kobayashi, K Ide, M Ohira, H Tahara, S Shimizu, Y Saeki, H Sakai, T Yano, H Ohdan
BACKGROUND: The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure. METHODS: We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28060025/antibody-mediated-rejection-what-is-the-clinical-relevance
#15
Rachel Hogen, Joseph DiNorcia, Kiran Dhanireddy
PURPOSE OF REVIEW: The review outlines the diagnosis, clinical implications, and treatment strategies for acute and chronic antibody-mediated rejection (AMR) after orthotopic liver transplantation (OLT). RECENT FINDINGS: A combination of clinical work-up, histopathology, C4d staining, and donor-specific antibody (DSA) should be used to diagnose AMR. The differential diagnosis for idiopathic fibrosis now includes chronic AMR. Characterization of pathogenic DSA continues to progress...
April 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28006867/differential-profile-of-activated-regulatory-t-cell-subsets-and-micrornas-in-tolerant-liver-transplant-recipients
#16
B Revilla-Nuin, A de Bejar, L Martínez-Alarcón, J I Herrero, C M Martínez-Cáceres, P Ramírez, A Baroja-Mazo, J A Pons
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...
December 22, 2016: Liver Transplantation
https://www.readbyqxmd.com/read/27965672/hereditary-angioedema-as-a-metabolic-liver-disorder-novel-therapeutic-options-and-prospects-for-cure
#17
Rohan Ameratunga, Adam Bartlett, John McCall, Richard Steele, See-Tarn Woon, Constance H Katelaris
Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by mutations of the SERPING1 or the Factor 12 genes. It is potentially fatal, particularly if not identified at an early stage. Apart from androgens, which are contraindicated in children and in pregnant women, a range of effective, albeit very expensive treatments have recently become available for HAE patients. The cost of these new treatments is beyond the reach of most developing countries. At this time, there is no cure for the disorder...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27942590/early-cytokine-signatures-of-ischemia-reperfusion-injury-in-human-orthotopic-liver-transplantation
#18
Rebecca A Sosa, Ali Zarrinpar, Maura Rossetti, Charles R Lassman, Bita V Naini, Nakul Datta, Ping Rao, Nicholas Harre, Ying Zheng, Roberto Spreafico, Alexander Hoffmann, Ronald W Busuttil, David W Gjertson, Yuan Zhai, Jerzy W Kupiec-Weglinski, Elaine F Reed
BACKGROUND. Orthotopic liver transplant (OLT) is the primary therapy for end-stage liver disease and acute liver failure. However, ischemia/reperfusion injury (IRI) can severely compromise allograft survival. To understand the evolution of immune responses underlying OLT-IRI, we evaluated longitudinal cytokine expression profiles from adult OLT recipients before transplant through 1 month after transplant. METHODS. We measured the expression of 38 cytokines, chemokines, and growth factors in preoperative and postoperative recipient circulating systemic blood (before transplant and 1 day, 1 week, and 1 month after transplant) and intraoperative portal blood (before and after reperfusion) of 53 OLT patients and analyzed this expression in relation to biopsy-proven IRI (n = 26 IRI+; 27 IRI-), clinical liver function tests early (days 1-7) after transplant, and expression of genes encoding cytokine receptors in biopsies of donor allograft taken before and after reperfusion...
December 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27924436/resolution-of-multifocal-epstein-barr-virus-related-smooth-muscle-tumor-in-a-patient-with-gata2-deficiency-following-hematopoietic-stem-cell-transplantation
#19
Mark Parta, Jennifer Cuellar-Rodriguez, Alexandra F Freeman, Juan Gea-Banacloche, Steven M Holland, Dennis D Hickstein
We performed allogeneic hematopoietic stem cell transplantation in a patient with GATA2 deficiency and an Epstein-Barr virus (EBV)-related spindle cell tumor involving the liver and possibly bone. He received a matched-related donor transplant with donor peripheral blood stem cells following a myeloablative conditioning regimen. He achieved rapid and high levels of donor engraftment and had complete reversal of the clinical and immunologic phenotype of MonoMAC/GATA2 deficiency and eradication of the EBV tumors after 3 years of follow-up...
January 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/27911488/hepatocellular-carcinoma-as-an-emerging-morbidity-in-the-thalassemia-syndromes-a-comprehensive-review
#20
REVIEW
Hassan M Moukhadder, Racha Halawi, Maria Domenica Cappellini, Ali T Taher
The incidence of hepatocellular carcinoma (HCC) in patients with thalassemia is on the rise. The 2 well recognized HCC risk factors in thalassemia are iron overload and chronic viral infection with hepatitis C. The carcinogenicity of iron is related to its induction of oxidative damage, which results in genotoxicity, and to immunologic dysregulation, which attenuates cancer immune surveillance. Chronic hepatitis B and C infections lead to necroinflammation, which can prompt progression to HCC, but an independent role of hepatitis B virus in hepatic carcinogenesis among patients with thalassemia has not been demonstrated...
December 1, 2016: Cancer
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