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Liver transplant tolerance

Wubing He, Lihong Chen, Lin Zheng, Liuping Luo, Lingyun Gao
BACKGROUND: Dendritic cells (DCs) and regulatory T (Treg) cells are crucial for inducing immune tolerance. However, the suppressive function of infused Treg cells and immature DCs (imDCs) following solid organ transplantation remains unclear. METHODS: ImDCs derived from DA-donor rats and Treg cells isolated from spleens of Lewis rats were prepared. A heterotopic liver transplantation model was established to examine the immune tolerance effects of infusion of Treg-imDCs, imDCs and Treg cells individually...
October 17, 2016: Molecular Immunology
Yundong Qu, Ying Guo, Tao Li, Qian Ye, Chao Sun, Lei Wang, Baohua Yang
BACKGROUND AND AIM: To assess the efficacy and safety of sofosbuvir-based interferon-free therapies in liver transplantation recipients with hepatitis C virus infection recurrence. METHODS: A systematic literature search was conducted in PubMed, EMBASE, Web of Science, and CENTRAL on the Cochrane Library without time or language limitation. The search strategy used was "sofosbuvir AND transplantation". Sustained virologic response at 12 weeks after the end of treatment (SVR12) rate, incidence of serious adverse events (SAEs) and/or adverse events (AEs), discontinuation rate with 95% confidence intervals (CI) were pooled with random-effects model...
October 17, 2016: Journal of Gastroenterology and Hepatology
L Benítez-Gutiérrez, C de Mendoza, I Baños, A Duca, A Arias, A Treviño, S Requena, M J Citores, V Cuervas-Mons
New direct-acting antivirals (DAAs) have dramatically improved sustained virologic response (SVR) rates in patients treated for chronic hepatitis C. Although the safety of these agents has been very good in registration trials, unexpected side effects have been reported after much broader use of DAAs on marketing. We retrospectively examined all liver transplant recipients with chronic hepatitis C that received sofosbuvir-based regimens at our clinic. A total of 24 liver transplant recipients with recurrent chronic hepatitis C had received sofosbuvir up to April 2015...
September 2016: Transplantation Proceedings
C M Cruz, S Pereira, J Gandara, S Ferreira, V Lopes, J Daniel, H P Miranda
Calcineurin inhibitors (CNI) are the base of immunosuppressive regimens in liver transplantation but they are associated with significant side effects, namely nephrotoxicity, which leads to increased morbidity and mortality. Through time, mycophenolate mofetil (MMF) as monotherapy has been suggested as an alternative in patients with CNI-related toxicity, but still no consensus has been reached as to its efficacy. We have evaluated the safety, efficacy, and tolerability of MMF monotherapy in selected patients, developing CNI-associated events, focusing primarily on kidney dysfunction...
September 2016: Transplantation Proceedings
Cyril Garrouste, Dany Anglicheau, Nassim Kamar, Claire Bachelier, Joseph Rivalan, Bruno Pereira, Sophie Caillard, Julien Aniort, Philippe Gatault, Martin Soubrier, Johnny Sayegh, Charlotte Colosio, Anthony Buisson, Eric Thervet, Nicolas Bouvier, Anne Elisabeth Heng
Anti-tumor necrosis factor-α (TNFα) therapy has improved the prognosis of many chronic inflammatory diseases. It appears to be well-tolerated by liver-transplant patients. However, their use and their safety in kidney-transplant patients have yet to be determined.In this retrospective study, we identified 16 adult kidney-transplant patients aged 46.5 years (34-51.8) who received anti-TNFα therapy from 7 kidney transplantation centers. The indications for this treatment included: chronic inflammatory bowel disease (n = 8), inflammatory arthritis (n = 5), AA amyloidosis (n = 1), psoriasis (n = 1), and microscopic polyangiitis (n = 1)...
October 2016: Medicine (Baltimore)
Jong Man Kim, Choon Hyuck David Kwon, Jae-Won Joh, Gyu-Seong Choi, Jae Berm Park, Eun-Suk Kang, Sung Joo Kim, Suk-Koo Lee
PURPOSE: T lymphocytes are an essential component of allograft rejection and tolerance. The aims of the present study are to analyze the characteristics of T-cell subsets between ABO-incompatible living donor liver transplantation (ABO-I LDLT) and ABO-compatible LDLT (ABO-C LDLT). MATERIALS AND METHODS: Between April 2013 and June 2014, 61 patients underwent adult LDLT. ABO-I LDLT patients received rituximab and all patients received basiliximab as induction therapy and tacrolimus as maintenance therapy...
October 13, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
L Y Ping, Y Q Song, W Zheng, X P Wang, Y Xie, N J Lin, M F Tu, Z T Ying, W P Liu, C Zhang, L J Deng, J Zhu
Objective: To investigate the efficacy and survival of the DICE regimen (cisplatin, ifosfamide, etoposide, dexamethasone) for relapsed and refractory NHL. Methods: Clinical data of 97 relapsed and refractory NHL patients treated with DICE regimen in Peking University Cancer Hospital between Sep 1. 2008 and Dec 31. 2013 were retrospectively analyzed, and then we evaluate the efficacy and safety of DICE regimen. Results: ① There were 64 males and 33 females with a median age of 49 years. The most common pathological type was DLBCL (73...
September 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Jean C Emond, Adam D Griesemer
No abstract text is available yet for this article.
October 7, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Christopher L Bowlus, James T Kenney, Gary Rice, Robert Navarro
BACKGROUND: Chronic liver disease and cirrhosis are a leading cause of morbidity and mortality in the United States. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis and which has been designated an orphan condition, is a chronic autoimmune disease resulting in the destruction of the small bile ducts in the liver. Without effective treatment, disease progression frequently leads to liver failure and death. Until May 2016, the only FDA-approved treatment for PBC was ursodiol (UDCA), an oral hydrophilic bile acid, which can slow progression of liver damage due to PBC...
October 2016: Journal of Managed Care & Specialty Pharmacy
Alberto Baroja-Mazo, Beatriz Revilla-Nuin, Pascual Parrilla, Laura Martínez-Alarcón, Pablo Ramírez, José Antonio Pons
Transplantation is the optimal treatment for end-stage organ failure, and modern immunosuppression has allowed important progress in short-term outcomes. However, immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus, a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor FoxP3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis...
September 14, 2016: World Journal of Gastroenterology: WJG
Giovanni Luca, Iva Arato, Francesca Mancuso, Mario Calvitti, Giulia Falabella, Giuseppe Murdolo, Giuseppe Basta, Don F Cameron, Barbara C Hansen, Francesca Fallarino, Tiziano Baroni, Maria Chiara Aglietti, Cristina Tortoioli, Maria Bodo, Riccardo Calafiore
BACKGROUND: Increased abdominal fat and chronic inflammation in the expanded adipose tissue of obesity contribute to the development of insulin resistance and type 2 diabetes mellitus (T2D). The emerging immunoregulatory and anti-inflammatory properties of Sertoli cells have prompted their application to experimental models of autoimmune/inflammatory disorders, including diabetes. The main goal of this work was to verify whether transplantation of microencapsulated prepubertal porcine Sertoli cells (MC-SC) in the subcutaneous abdominal fat depot of spontaneously diabetic and obese db/db mice (homozygous for the diabetes spontaneous mutation [Lepr(db) ]) would: (i) improve glucose homeostasis and (ii) modulate local and systemic immune response and adipokines profiles...
September 27, 2016: Xenotransplantation
Jong-Min Kim, Jun-Seop Shin, Byoung-Hoon Min, Hyun-Je Kim, Jung-Sik Kim, Il-Hee Yoon, Won-Young Jeong, Ga-Eul Lee, Min-Sun Kim, Ju-Eun Kim, Sang-Man Jin, Chung-Gyu Park
BACKGROUND: Diabetes mellitus (DM) model using streptozotocin (STZ) which induces chemical ablation of β cell in the pancreas has been widely used for various research purposes in non-human primates. However, STZ has been known to have a variety of adverse effects such as nephrotoxicity, hepatotoxicity, and even mortality. The purpose of this study is to report DM induction by STZ, toxicity associated with STZ and procedure and complication of exogenous insulin treatment for DM management in rhesus monkeys (Macaca mulatta) that are expected to be transplanted with porcine islets within 2 months...
September 27, 2016: Xenotransplantation
Aditya Bansal, Jay K Bhama, Rajan Patel, Sapna Desai, Stacy A Mandras, Hamang Patel, Tyrone Collins, John P Reilly, Hector O Ventura, P Eugene Parrino
BACKGROUND: Outcomes of traditional mechanical support paradigms (extracorporeal membrane oxygenation, intraaortic balloon pump [IABP], and permanent left ventricular assist device [LVAD]) in acute decompensated heart failure have generally been suboptimal. Novel approaches, such as minimally invasive LVAD therapy (Impella 5.0 device), promise less invasive but equivalent hemodynamic support. However, it is yet unknown whether the outcomes with such devices support widespread acceptance of this new technology...
2016: Ochsner Journal
Aimee G Kim, Jesse D Vrecenak, Matthew M Boelig, Linda Eissenberg, Michael P Rettig, John S Riley, Matthew S Holt, Michael A Conner, Stavros P Loukogeorgakis, Haiying Li, John F DiPersio, Alan W Flake, William H Peranteau
In utero hematopoietic cell transplantation (IUHCT) is a novel nonmyeloablative approach that results in donor specific tolerance and mixed allogeneic chimerism. Clinical application is limited by low levels of donor cell engraftment. Competition from endogenous hematopoietic stem cells (HSCs) for limited "space" in fetal hematopoietic organs remains a significant barrier to successful IUHCT. AMD3100, a CXCR4 inhibitor, and firategrast, an α4β1 and α4β7 integrin inhibitor (α4β1/7) have been shown to disrupt HSC retention in the postnatal hematopoietic niche (HN)...
September 20, 2016: Blood
Ben Ma, Jing-Yue Yang, Wen-Jie Song, Rui Ding, Zhuo-Chao Zhang, Hong-Chen Ji, Xuan Zhang, Jian-Lin Wang, Xi-Sheng Yang, Kai-Shan Tao, Ke-Feng Dou, Xiao Li
Allograft tolerance is the ultimate goal in the field of transplantation immunology. Immature dendritic cells (imDCs) play an important role in establishing tolerance but have limitations, including potential for maturation, short lifespan in vivo and short storage times in vitro. However, exosomes (generally 30-100 nm) from imDCs (imDex) retain many source cell properties and may overcome these limitations. In previous reports, imDex prolonged the survival time of heart or intestine allografts. However, tolerance or long-term survival was not achieved unless immune suppressants were used...
2016: Scientific Reports
Pierluigi Toniutto, Alberto Zanetto, Alberto Ferrarese, Patrizia Burra
Liver transplantation is an effective and widely used therapy for several patients with acute and chronic liver diseases. The discrepancy between the number of patients on the waiting list and available donors remains the key issue and is responsible for the high rate of waiting list mortality. The recent news is that the majority of patients with hepatitis C virus related liver disease will be cured by new antivirals therefore we should expect soon a reduction in the need of liver transplantation for these recipients...
September 16, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Justin Parizo, Ashish Sarraju, Joshua W Knowles
Both HeFH and HoFH require dietary and lifestyle modification. Pharmacotherapy of adult HeFH patients is largely driven by the American Heart Association (AHA) algorithm. A high-potency statin is started initially with a goal low-density lipoprotein cholesterol (LDL-C) reduction of >50 %. The LDL-C target is adjusted to <100 or <70 mg/dL in subjects with coronary artery disease (CAD) with ezetimibe being second line. If necessary, a third adjunctive therapy, such as a PSCK9 inhibitor (not yet approved in children) or bile acid-binding resin, can be added...
November 2016: Current Treatment Options in Cardiovascular Medicine
R Flisiak, E Janczewska, M Wawrzynowicz-Syczewska, J Jaroszewicz, D Zarębska-Michaluk, K Nazzal, B Bolewska, J Bialkowska, H Berak, K Fleischer-Stępniewska, K Tomasiewicz, K Karwowska, K Rostkowska, A Piekarska, O Tronina, G Madej, A Garlicki, M Lucejko, A Pisula, E Karpińska, W Kryczka, A Wiercińska-Drapało, I Mozer-Lisewska, M Jabłkowski, A Horban, B Knysz, M Tudrujek, W Halota, K Simon
BACKGROUND: Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies. AIM: To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions. METHODS: Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics...
November 2016: Alimentary Pharmacology & Therapeutics
Vasileios Rafailidis, Annamaria Deganello, Tom Watson, Paul S Sidhu, Maria E Sellars
Contrast-enhanced Ultrasound (CEUS) represents a complementary technique to grey-scale and colour Doppler ultrasonography (US) which allows for real-time visualization and characterization of tissue perfusion. Its inherent advantages in the child makes US an ideal imaging modality; repeatability and good tolerance along with the avoidance of computed tomography (CT), a source of ionizing radiation, renders US imaging desirable. Although currently paediatric CEUS is principally used in an "off-label" manner, US contrast agents have received regulatory approval for assessment of paediatric focal liver lesions in the United States of America...
September 9, 2016: British Journal of Radiology
A Igarashi, W Tang, S Cure, I Guerra, L Marié, M Lopresti, K Tsutani
OBJECTIVE: Across Japan, around 2 million people are infected with hepatitis C virus (HCV) with long-term complications such as cirrhosis, hepatocellular carcinoma (HCC) and liver transplant (LT). Current treatment options have several limitations due to side effects, interferon intolerability and ineligibility, long treatment durations and low sustained virological responses (SVR) rates, especially for the most severe patients. Sofosbuvir (SOF) is the first nucleotide analog NS5B polymerase inhibitor with pan-genotypic activity...
September 8, 2016: Current Medical Research and Opinion
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