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Liver transplant tolerance

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https://www.readbyqxmd.com/read/27917261/anti-hepatitis-c-virus-drugs-and-kidney
#1
REVIEW
Paul Carrier, Marie Essig, Marilyne Debette-Gratien, Denis Sautereau, Annick Rousseau, Pierre Marquet, Jérémie Jacques, Véronique Loustaud-Ratti
Hepatitis C virus (HCV) mainly targets the liver but can also induce extrahepatic manifestations. The kidney may be impacted via an immune mediated mechanism or a cytopathic effect. HCV patients are clearly at a greater risk of chronic kidney disease (CKD) than uninfected patients are, and the presence of CKD increases mortality. Interferon-based therapies and ribavirin are difficult to manage and are poorly effective in end-stage renal disease and hemodialysis. These patients should be given priority treatment with new direct anti-viral agents (DAAs) while avoiding peginterferon and ribavirin...
November 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27914923/alloantigen-gene-transfer-to-hepatocytes-promotes-tolerance-to-pancreatic-islet-graft-by-inducing-cd8-regulatory-t-cells
#2
Valentin Le Guen, Jean-Paul Judor, Françoise Boeffard, Vanessa Gauttier, Nicolas Ferry, Jean-Paul Soulillou, Sophie Brouard, Sophie Conchon
BACKGROUND & AIM: Induction of donor-specific immune tolerance is a good alternative to chronic life-long immunosuppression for transplant patients. Donor major histocompatibility complex (MHC) molecules represent the main targets of the allogeneic immune response of transplant recipients. Liver-targeted gene transfer with viral vectors induces tolerance toward the encoded antigen. The aim of this work was to determine whether alloantigen gene transfer to hepatocytes induces tolerance and promotes graft acceptance...
November 30, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27909287/elevated-fasting-plasma-glucose-before-liver-transplantation-is-associated-with-lower-post-transplant-survival
#3
Emi Katsura, Tatsuki Ichikawa, Naota Taura, Hisamitsu Miyaaki, Satoshi Miuma, Hidetaka Shibata, Takuya Honda, Masaaki Hidaka, Akihiko Soyama, Fuminao Takeshima, Susumu Eguchi, Kazuhiko Nakao
BACKGROUND The risk of liver cirrhosis is higher among individuals with diabetes mellitus, and a cirrhotic patient with diabetes may have a poorer prognosis after liver transplantation compared to a patient without diabetes. Thus, we evaluated whether fasting plasma glucose prior to receiving a liver transplant was a prognostic factor for post-transplant survival. MATERIAL AND METHODS Ninety-one patients received a living donor liver transplant between November 2005 and December 2012. Patients were considered diabetic if they were prescribed diabetes medications or had impaired glucose tolerance as measured by an oral glucose tolerance test...
December 2, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27906834/successful-continuation-of-hcv-treatment-following-liver-transplantation
#4
Carlos Fernández Carrillo, Gonzalo Crespo, Juan de la Revilla, Lluís Castells, Maria Buti, José Luis Montero, Emilio Fábrega, Inmaculada Fernández, Cristina Serrano-Millán, Victoria Hernández, José Luis Calleja, María-Carlota Londoño
BACKGROUND: Guidelines recommend that patients with hepatitis C virus (HCV)-related liver disease be treated for HCV before liver transplant (LT) to eliminate the virus prior to surgery. However, the unpredictability of donor organ availability may limit treatment duration. Interruption of HCV treatment with resumption post-LT is one potential solution which has not been investigated widely. METHODS: Patients from 5 clinical centres included in the large, national, noninterventional Hepa-C registry who started treatment with direct-acting antiviral agents (DAAs) while awaiting LT were identified retrospectively and followed up prospectively...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27905019/multi-disciplinary-concurrent-management-of-recurrent-hepatocellular-therapy-is-superior-to-sequential-therapy
#5
Tyler D Fields, Prejesh Philips, Charles R Scoggins, Cliff Tatum, Lawrence Kelly, Kelly M McMasters, Robert C G Martin
BACKGROUND: Recurrent hepatocellular carcinoma after a patient's initial therapy, whether it is transplantation, resection, or ablation, remains a challenging clinical problem. Since recurrence occurs in 70% of all initially treated disease within 5 years, optimal management to treat this recurrence is needed. Currently, a bias exists toward mono-therapy (i.e., ablation alone, hepatic arterial therapy alone, or sorafenib therapy alone) instead of concurrent sequential therapy-as is common in other primary and metastatic disease to the liver...
November 30, 2016: World Journal of Surgery
https://www.readbyqxmd.com/read/27900108/high-dose-chemotherapy-with-autologous-peripheral-blood-stem-cell-transplantation-for-choriocarcinoma-a-case-report-and-literature-review
#6
Eiko Yamamoto, Kaoru Niimi, Kayo Fujikake, Tetsuya Nishida, Makoto Murata, Ayako Mitsuma, Yuichi Ando, Fumitaka Kikkawa
Choriocarcinoma is a malignant gestational trophoblastic neoplasia (GTN) and one of the curable types of gynecological cancer. However, 10% of choriocarcinoma patients have a poor prognosis, particularly when they have metastasis, apart from pulmonary metastasis, or do not go into remission by the second chemotherapeutic regimen. We herein present the case of a 36-year-old patient who had choriocarcinoma with metastases to the lungs, liver and kidneys. The 5th and 6th regimens with cisplatin for choriocarcinoma failed and the patient developed brain metastases...
November 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27896858/efficacy-and-safety-of-simeprevir-and-sofosbuvir-with-and-without-ribavirin-in-subjects-with-recurrent-genotype-1-hepatitis-c-post-orthotopic-liver-transplant-the-randomized-galaxy-study
#7
Jacqueline G O'Leary, Robert J Fontana, Kimberly Brown, James R Burton, Roberto Firpi-Morell, Andrew Muir, Christopher O'Brien, Mordechai Rabinovitz, K Rajender Reddy, Robert Ryan, Adam Shprecher, Shirley Villadiego, Avinash Prabhakar, Robert S Brown
This prospective, randomized, phase 2 study in subjects with recurrent hepatitis C virus (HCV) genotype 1 post-orthotopic liver transplant evaluated once-daily simeprevir 150mg+sofosbuvir 400mg, with and without ribavirin 1,000mg. Primary endpoint was proportion of subjects with Week 12 sustained virologic response (SVR12). Thirty-three subjects without cirrhosis were randomized 1:1:1 into three arms (stratified by geno/subtype and Q80K): Arm 1, simeprevir+sofosbuvir+ribavirin, 12 weeks; Arm 2, simeprevir+sofosbuvir, 12 weeks; Arm 3, simeprevir+sofosbuvir, 24 weeks; 13 additional subjects (2 with cirrhosis, 11 without cirrhosis) entered Arm 3...
November 29, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27878737/sebelipase-alfa-a-review-in-lysosomal-acid-lipase-deficiency
#8
James E Frampton
Sebelipase alfa (Kanuma(®), Kanuma™), the first commercially available recombinant human lysosomal acid lipase (LAL), is approved in various countries worldwide, including those of the EU, the USA and Japan, as a long-term enzyme replacement therapy for patients diagnosed with LAL deficiency (LAL-D), an ultra-rare, autosomal recessive, progressive metabolic liver disease. In an ongoing study in nine infants presenting with early-onset LAL-D (Wolman disease), open-label treatment with sebelipase alfa significantly improved 1-year survival compared with historical controls...
November 23, 2016: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/27878476/management-of-post-liver-transplant-recurrence-of-hepatitis-c
#9
Justin Taylor, Paula Cox-North, Charles S Landis
Cirrhosis due to chronic hepatitis C (HCV) is the leading indication for liver transplantation in North America and Europe. HCV re-infection post-transplant is nearly universal and if left untreated negatively affects patient and graft survival. Until recently, treatment options for HCV were limited to interferon (IFN)-based therapies which had low sustained viral response (SVR) rates and were poorly tolerated in the post-transplant setting. In the last 3 years, the promise of the directly acting antivirals (DAAs) for the treatment of HCV has been fulfilled with high sustained viral response (SVR) rates and a low side effect profile demonstrated in both registration trials and real-world studies...
November 23, 2016: Drugs
https://www.readbyqxmd.com/read/27874250/immunosuppression-in-pediatric-liver-transplant-recipients-unique-aspects
#10
REVIEW
Miloh Tamir, Barton Andrea, Wheeler Justin, Pham Yen, Hewitt Winston, Keegan Tara, Sanchez Christine, Bulut Pinar, Goss John
Pediatric liver transplantation has experienced improved outcomes over the last 50 years. This can be attributed in part to establishing optimal use of immunosuppressive agents to achieve a balance between minimizing the risks of allograft rejection and infection. The management of immunosuppression in children is generally more complex and can be challenging when compared to the use of these agents in adult liver transplant patients. Physiologic differences in children alter the pharmacokinetics of immunosuppressive agents, which affects absorption, distribution, metabolism and drug excretion...
November 22, 2016: Liver Transplantation
https://www.readbyqxmd.com/read/27867515/the-cd8-t-cell-response-during-tolerance-induction-in-liver-transplantation
#11
REVIEW
Yik Chun Wong, Geoffrey W McCaughan, David G Bowen, Patrick Bertolino
Both experimental and clinical studies have shown that the liver possesses unique tolerogenic properties. Liver allografts can be spontaneously accepted across complete major histocompatibility mismatch in some animal models. In addition, some liver transplant patients can be successfully withdrawn from immunosuppressive medications, developing 'operational tolerance'. Multiple mechanisms have been shown to be involved in inducing and maintaining alloimmune tolerance associated with liver transplantation. Here, we focus on CD8 T-cell tolerance in this setting...
October 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27860156/hepatotoxicity-of-statins-and-other-lipid-lowering-agents
#12
REVIEW
Einar S Björnsson
Statins are generally well tolerated and adverse effects are relatively rare. Clinical trials are underpowered to detect uncommon adverse effects such as idiosyncratic drug-induced liver injury. This review is aimed at covering the current knowledge on the hepatotoxicity associated with statins and other lipid lowering drugs. Both atorvastatin and simvastatin have been associated with more than 50 case reports of liver injury and other statins have been implicated in this type of liver injury as well. Idiosyncratic liver injury due to statins has been reported to occur 1...
November 8, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27825643/-sofosbuvir-and-daclatasvir-combination-therapy-in-hemodialysis-patient-with-liver-transplantation
#13
Mourad Hachicha, Danielle Botta-Fridlund
We report a case of sustained remission of a liver transplant patient infected with hepatitis C virus (HCV) genotype 1 undergoing hemodialysis treatment. Oral treatment regimen of the HCV infection consists of a combination of sofosbuvir 400 mg after each hemodialysis session and daclatasvir 60 mg daily, for a period of 3 months. Laboratory testing indicate that the combination regimen was well-tolerated with no sign of drug-drug interaction. Confirmation of these clinical observations in large clinical studies may help improve morbidity and decrease mortality outcome in patients infected with HCV and undergoing hemodialysis treatment...
November 4, 2016: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/27805501/tolerance-in-solid-organ-transplant
#14
Richard N Fine
Immunotolerance, which is nonimmunologic reactivity to specific tissue, was demonstrated in animals in the 1950s. However, despite assiduous efforts, it has not been reproduced in human solid-organ transplant to date. Fortuitously, clinical operational tolerance, which is stable graft function for > 1 year with no immunosuppression, has been demonstrated, primarily in a few nonadherent recipients of kidney and liver transplant. Vigorous efforts to identify a biomarker to distinguish recipients with clinical operational tolerance from nontolerant recipients have so far not been successful...
November 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27804912/emerging-therapies-for-acute-intermittent-porphyria
#15
Antonio Fontanellas, Matías A Ávila, Pedro Berraondo
Acute intermittent porphyria (AIP) is an autosomal dominant metabolic disease caused by hepatic deficiency of hydroxymethylbilane synthase (HMBS), the third enzyme of the heme synthesis pathway. The dominant clinical feature is acute neurovisceral attack associated with high production of potentially neurotoxic porphyrin precursors due to increased hepatic heme consumption. Current Standard of Care is based on a down-regulation of hepatic heme synthesis using heme therapy. Recurrent hyper-activation of the hepatic heme synthesis pathway affects about 5% of patients and can be associated with neurological and metabolic manifestations and long-term complications including chronic kidney disease and increased risk of hepatocellular carcinoma...
November 2, 2016: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/27783460/efficacy-of-hydrodynamic-il10-gene-transfer-in-human-liver-segments-with-interest-in-transplantation
#16
Luis Sendra Gisbert, Antonio Miguel Matas, Luis Sabater Ortí, María José Herrero Cervera, Laura Sabater Olivas, Eva María Montalvá Orón, Matteo Frasson, Rafael Abargues López, Rafael López-Andújar, Eduardo García-Granero Ximénez, Salvador Francisco Aliño Pellicer
: Different diseases lead, during their advanced stages, to chronic or acute liver failure, whose unique treatment consists in organ transplantation. The success of intervention is limited by host immune response and graft rejection. Immunosuppressant drugs permitted improving organ transplantation but they cannot completely solve the problem and their management is delicate, especially during the early stages of treatment. Thus, new tools to set an efficient modulation of immune response are required...
October 26, 2016: Liver Transplantation
https://www.readbyqxmd.com/read/27781378/mass-cytometry-reveals-a-distinct-immunoprofile-of-operational-tolerance-in-pediatric-liver-transplantation
#17
Audrey H Lau, Matthew J Vitalone, Kelly Haas, Todd Shawler, Carlos O Esquivel, William E Berquist, Olivia M Martinez, Ricardo O Castillo, Sheri M Krams
Long-term IS in transplant patients has significant morbidity, poorer quality of life, and substantial economic costs. TOL, defined as graft acceptance without functional impairment in the absence of IS, has been achieved in some pediatric LT recipients. Using mass cytometry, peripheral blood immunotyping was performed to characterize differences between tolerant patients and patients who are stable on single-agent IS. Single-cell mass cytometry was performed using blood samples from a single-center pediatric LT population of operationally tolerant patients to comprehensively characterize the immune cell populations in the tolerant state compared with patients on chronic low-dose IS...
October 26, 2016: Pediatric Transplantation
https://www.readbyqxmd.com/read/27768010/update-on-hepatitis-c-treatment-systematic-review-of-clinical-trials
#18
Manan Jhaveri, Nicholas Procaccini, Kris V Kowdley
Chronic Hepatitis C is a major public health problem. The chronicity of the Hepatitis C can lead to advanced liver disease, cirrhosis and even hepatocellular carcinoma. Chronic hepatitis C is the leading indication of for liver transplantation in the United States. Since the introduction of directly acting antiviral agents (DAAs), there have been there have been dramatic advances in treatment of hepatitis C in terms of tolerability, duration of therapy with significant increases in the rates of sustained virology response (SVR)...
October 21, 2016: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/27764710/prolonged-survival-effects-induced-by-immature-dendritic-cells-and-regulatory-t-cells-in-a-rat-liver-transplantation-model
#19
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
https://www.readbyqxmd.com/read/27749979/efficacy-and-safety-of-sofosbuvir-based-interferon-free-therapies-for-hepatitis-c-in-liver-transplant-recipients
#20
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
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