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Liver transplant tolerance

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https://www.readbyqxmd.com/read/28433098/wilson-disease-in-children
#1
Eve A Roberts, Piotr Socha
Wilson disease (WD) is an inherited disorder mainly of hepatocellular copper disposition, due to dysfunction of the Wilson ATPase, a P1B-ATPase encoded by the gene ATP7B. In children, as in older age brackets, clinical disease is highly diverse. Although hepatic disease is the common presentation in children/adolescents, neurologic, psychiatric, and hematologic clinical presentations do occur. Very young children may have clinically evident liver disease due to WD. Early diagnosis, preferably when the child/adolescent is asymptomatic, is most likely to result in near-normal longevity with generally good health so long as the patient tolerates effective medication, is adherent to the lifelong treatment regimen, and has consistent access to the medication...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28412754/efficacy-and-safety-of-a-reduced-calcineurin-inhibitor-dose-combined-with-mycophenolate-mofetil-in-liver-transplant-patients-with-chronic-renal-dysfunction
#2
Pusen Wang, Weitao Que, Hao Li, Lvnan Yan, Zhiren Fu, Qifa Ye, Guihua Chen, Kefeng Dou, Shichun Lu, Zhanyu Yang, Zhijun Zhu, Zhihai Peng, Lin Zhong
Calcineurin inhibitors (CNIs) are frequently given at a reduced dose in combination with mycophenolate mofetil (MMF) to avoid nephrotoxicity, but the optimal reduction in CNI dose has not been established. In this prospective, open-label, multicenter study, liver transplant recipients with chronic renal dysfunction who were administered a CNI-based immunosuppressive regimen were included in the intent-to-treat (ITT) population. The primary endpoint was declination in renal function, which was defined as a ≥ 20% decrease in the glomerular filtration rate during the year following regimen adjustment...
February 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404073/optimum-timing-of-treatment-for-hepatitis-c-infection-relative-to-liver-transplantation
#3
REVIEW
Audrey Coilly, Bruno Roche, Jean-Charles Duclos-Vallée, Didier Samuel
The approval of direct-acting antiviral agents that may be given orally in an interferon-free regimen has greatly changed the landscape of treatment for hepatitis C virus (HCV) infection, especially for patients with the most severe disease, who have decompensated cirrhosis, or who are waiting for or have undergone liver transplantation. Treatment with interferon proved to be ineffective and poorly tolerated because of high risks of infection and transplant rejection. The availability of new drugs poses new questions about the optimum time to give treatment to prevent HCV recurrence, taking into account efficacy, tolerance, and drug-drug interactions...
October 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28396749/an-hcv-positive-recipient-of-an-hcv-positive-donor-liver-successfully-treated-before-and-immediately-after-liver-transplant-with-daclatasvir-sofosbuvir-and-ribavirin
#4
Fred Poordad, Eric Lawitz, Julio A Gutierrez, Juan Guerrero, Kermit Speeg, Eugene S Swenson
This case suggests that initiation of HCV therapy immediately after liver transplantation with well-tolerated, all-oral regimens may achieve a virologic cure in HCV-positive recipients, thus preventing post-transplant HCV recurrence and associated disease progression. This strategy may broaden utilization of HCV-positive donor livers, potentially including HCV-negative transplant recipients.
April 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28382751/treatment-of-hcv-infection-in-liver-transplant-recipients-with-ledipasvir-and-sofosbuvir-without-ribavirin
#5
A A Pillai, R Maheshwari, R Vora, J P Norvell, R Ford, S Parekh, N Cheng, A Patel, N Young, J R Spivey, O Mgbemena, J P Wedd
BACKGROUND: Ledipasvir and Sofosbuvir is a well-tolerated regimen with high sustained virological response (SVR) rates in pre-liver transplant patients infected with chronic hepatitis C virus (HCV), but data in liver transplant recipients outside of clinical trials is limited. AIMS: To address this knowledge gap and assess SVR rates without the use of ribavirin in liver transplant recipients METHODS: This is a retrospective study examining the treatment of 75 post-liver transplant recipients with ledipasvir and sofosbuvir without ribavirin...
April 6, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28377772/treatment-of-pediatric-acute-graft-versus-host-disease-lessons-from-primary-immunodeficiency
#6
REVIEW
Aisling M Flinn, Andrew R Gennery
Allogeneic hematopoietic stem cell transplant (HSCT) is used to treat increasing numbers of malignant and non-malignant disorders. Despite significant advances in improved human leukocyte antigens-typing techniques, less toxic conditioning regimens and better supportive care, resulting in improved clinical outcomes, acute graft-versus-host disease (aGvHD) continues to be a major obstacle and, although it principally involves the skin, gastrointestinal tract, and liver, the thymus is also a primary target. An important aim following HSCT is to achieve complete and durable immunoreconstitution with a diverse T-cell receptor (TCR) repertoire to recognize a broad range of pathogens providing adequate long-term adaptive T-lymphocyte immunity, essential to reduce the risk of infection, disease relapse, and secondary malignancies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28371104/old-and-new-treatments-for-primary-biliary-cholangitis
#7
David Chascsa, Elizabeth J Carey, Keith D Lindor
Primary biliary cholangitis (formerly primary biliary cirrhosis) is a rare progressive cholestatic liver disease, whose hallmark features include a persistently elevated alkaline phosphatase level, presence of anti-mitochondrial antibodies and characteristic histology. Since 1998, ursodeoxycholic acid (UDCA), a bile acid, has been the only available therapeutic agent. Primary biliary cholangitis is associated with the development of end-stage liver disease, increased morbidity and mortality. UDCA has been shown to improve serum biochemistries, histology and delay the need for liver transplantation...
April 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28369489/clinical-effectiveness-of-early-posaconazole-suspension-pre-emptive-therapy-in-lung-transplant-recipients-the-alfred-s-experience
#8
Wirawan Jeong, Greg I Snell, Bronwyn J Levvey, Glen P Westall, C Orla Morrissey, Steven Ivulich, Chin Fen Neoh, Monica A Slavin, David C M Kong
Objectives: This study describes the clinical outcomes and therapeutic drug monitoring (TDM) following posaconazole suspension pre-emptive therapy in lung transplant (LTx) recipients. Methods: This was a single-centre, retrospective cohort study evaluating posaconazole suspension pre-emptive therapy in LTx recipients between January 2009 and December 2015. Results: Forty-two LTx recipients were prescribed posaconazole suspension pre-emptively...
March 22, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28358858/a-preclinical-evaluation-of-alternative-site-for-islet-allotransplantation
#9
Chengshi Wang, Xiaojiong Du, Sirong He, Yujia Yuan, Pengfei Han, Dan Wang, Younan Chen, Jingping Liu, Bole Tian, Guang Yang, Shounan Yi, Fabao Gao, Zhihui Zhong, Hongxia Li, Jingqiu Cheng, Yanrong Lu
The bone marrow cavity (BMC) has recently been identified as an alternative site to the liver for islet transplantation. This study aimed to compare the BMC with the liver as an islet allotransplantation site in diabetic monkeys. Diabetes was induced in Rhesus monkeys using streptozocin, and the monkeys were then divided into the following three groups: Group1 (islets transplanted in the liver with immunosuppressant), Group 2 (islets transplanted in the tibial BMC), and Group 3 (islets transplanted in the tibial BMC with immunosuppressant)...
2017: PloS One
https://www.readbyqxmd.com/read/28333015/role-of-stereotactic-body-radiation-therapy-before-orthotopic-liver-transplantation-retrospective-evaluation-of-pathologic-response-and-outcomes
#10
Edward Michael Mannina, Higinia Rosa Cardenes, Foster D Lasley, Benjamin Goodman, Jennifer Zook, Sandra Althouse, John Alvin Cox, Romil Saxena, Joseph Tector, Mary Maluccio
PURPOSE: To analyze the results of stereotactic body radiation therapy (SBRT) in patients with early-stage, localized hepatocellular carcinoma who underwent definitive orthotopic liver transplantation (OLT). METHODS AND MATERIALS: The subjects of this retrospective report are 38 patients diagnosed with hepatocellular carcinoma who underwent SBRT per institutional phase 1 to 2 eligibility criteria, before definitive OLT. Pre-OLT radiographs were compared with pathologic gold standard...
April 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28321272/future-of-liver-disease-in-the-era-of-direct-acting-antivirals-for-the-treatment-of-hepatitis-c
#11
REVIEW
Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Gian Lodovico Rapaccini, Maurizio Pompili, Antonio Gasbarrini
Hepatitis C virus (HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and well-tolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction...
March 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28319600/early-and-late-factors-impacting-patient-and-graft-outcome-in-pediatric-liver-transplantation-summary-of-an-espghan-monothematic-conference
#12
Valérie A McLin, Upton Allen, Olivia Boyer, John Bucuvalas, Michele Colledan, Maria-Cristina Cuturi, Lorenzo d'Antiga, Dominique Debray, Antal Dezsofi, Jean de Ville de Goyet, Anil Dhawan, Ozlem Durmaz, Christine Falk, Sandy Feng, Björn Fischler, Stéphanie Franchi-Abella, Esteban Frauca, Rainer Ganschow, Stephen Gottschalk, Nedim Hadzic, Loreto Hierro, Simon Horslen, Stefan Hubscher, Vincent Karam, Deirdre Kelly, Britta Maecker-Kolhoff, George Mazariegos, Patrick McKiernan, Anette Melk, Valerio Nobili, Funda Ozgenç, Raymond Reding, Marco Sciveres, Khalid Sharif, Piotr Socha, Christian Toso, Pietro Vajro, Anita Verma, Barbara E Wildhaber, Ulrich Baumann
As pediatric liver transplantation comes of age, experts gathered to discuss current paradigms and define gaps in knowledge warranting research to further improve patient and graft outcomes. Identified areas ripe for collaborative research include understanding the molecular and cellular mechanisms of tolerance and the role of donor-specific antibodies, considering ways to expand donor pool, minimizing long term side effects of immunosuppression, and fine-tuning surgical techniques to minimize biliary and vascular complications...
March 17, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28319445/nonclinical-pharmacology-toxicology-study-of-aav8-tbg-mldlr-and-aav8-tbg-hldlr-in-a-mouse-model-of-homozygous-familial-hypercholesterolemia
#13
Jenny A Greig, Maria P Limberis, Peter Bell, Shu-Jen Chen, Roberto Calcedo, Daniel J Rader, James M Wilson
The homozygous form of familial hypercholesterolemia (HoFH) is an excellent model for developing in vivo gene therapy in humans. The success of orthotropic liver transplantation in correcting the metabolic abnormalities in HoFH suggests that the correction of low-density lipoprotein receptor (LDLR) expression in hepatocytes via gene therapy should be sufficient for therapeutic efficacy. Vectors based on adeno-associated virus serotype 8 (AAV8) have been previously developed for liver-targeted gene therapy of a number of genetic diseases, including HoFH...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28318501/sorafenib-use-for-recurrent-hepatocellular-cancer-after-resection-or-transplantation-observations-from-a-us-regional-analysis-of-the-gideon-registry
#14
Robert C G Martin, Elizabeth Bruenderman, Allen Cohn, Bilal Piperdi, Rebecca Miksad, Jean-Francois Geschwind, Alec Goldenberg, Arun Sanyal, Ellen Zigmont, Svetlana Babajanyan, Pamela Foreman, Parvez Mantry, Brendan McGuire, Pierre Gholam
Treatment of unresectable recurrent hepatocellular carcinoma (HCC) in patients who recur after resection or orthotopic liver transplantation (OLT) remains a clinical challenge. One option is sorafenib, although little is known about its safety and tolerance in this unique patient population; therefore, we analyzed patients who underwent prior surgical resection and/or OLT and were treated with sorafenib in US cohort of GIDEON registry. In US, 645 patients were enrolled; 553 for intent to treat and 563 for safety...
April 2017: American Journal of Surgery
https://www.readbyqxmd.com/read/28314211/the-role-of-kupffer-cells-in-hepatic-diseases
#15
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/28301388/cold-storage-or-normothermic-perfusion-for-liver-transplantation-probable-application-and-indications
#16
Carlo D L Ceresa, David Nasralla, Simon Knight, Peter J Friend
PURPOSE OF REVIEW: Preservation of the liver via normothermic machine perfusion (NMP) is rapidly becoming an area of great academic and clinical interest. This review focuses on the benefits and limitations of NMP and where the role for static cold storage may lie. RECENT FINDINGS: Clinical studies have recently been published reporting the use of NMP in liver preservation for transplantation. They have described the technology to be well tolerated and feasible with potentially improved posttransplant outcomes...
March 15, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28295849/efficacy-safety-and-pharmacokinetics-of-simeprevir-daclatasvir-and-ribavirin-in-patients-with-recurrent-hepatitis-c-virus-genotype-1b-infection-after-orthotopic-liver-transplantation-the-phase-ii-saturn-study
#17
Xavier Forns, Marina Berenguer, Kerstin Herzer, Martina Sterneck, Maria Francesca Donato, Pietro Andreone, Stefano Fagiuoli, Tomasz Cieciura, Magdalena Durlik, Jose Luis Calleja, Zoe Mariño, Umesh Shukla, Thierry Verbinnen, Oliver Lenz, Sivi Ouwerkerk-Mahadevan, Monika Peeters, Katrien Janssen, Ronald Kalmeijer, Wolfgang Jessner
BACKGROUND: Recurrent hepatitis C virus (HCV) infection following liver transplantation is associated with accelerated progression to graft failure and reduced patient survival. METHODS: The Phase II, open-label SATURN study (NCT01938625) investigated the combination of simeprevir (SMV), daclatasvir (DCV), and ribavirin (RBV) administered for 24 weeks in 35 patients with recurrent HCV genotype (GT) 1b infection after orthotopic liver transplantation (OLT). RESULTS: High rates of both on-treatment and sustained virologic response 12 weeks after end of treatment (SVR12) were achieved in patients who were either treatment-naïve or had failed post-OLT treatment with peginterferon and RBV...
March 13, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28293378/hepatorenal-syndrome-update-on-diagnosis-and-therapy
#18
EDITORIAL
Juan G Acevedo, Matthew E Cramp
Hepatorenal syndrome (HRS) is a manifestation of extreme circulatory dysfunction and entails high morbidity and mortality. A new definition has been recently recommended by the International Club of Ascites, according to which HRS diagnosis relies in serum creatinine changes instead that on a fixed high value. Moreover, new data on urinary biomarkers has been recently published. In this sense, the use of urinary neutrophil gelatinase-associated lipocalin seems useful to identify patients with acute tubular necrosis and should be employed in the diagnostic algorithm...
February 28, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28293093/clinical-features-and-natural-history-of-cryptogenic-cirrhosis-compared-to-hepatitis-c-virus-related-cirrhosis
#19
Luca Rinaldi, Fabio Nascimbeni, Mauro Giordano, Chiara Masetti, Barbara Guerrera, Annalisa Amelia, Maria Chiara Fascione, Stefano Ballestri, Dante Romagnoli, Rosa Zampino, Riccardo Nevola, Enrica Baldelli, Natalina Iuliano, Valerio Rosato, Amedeo Lonardo, Luigi Elio Adinolfi
AIM: To characterize natural history of cryptogenic cirrhosis (CC) and compare its clinical features and outcomes to those of hepatitis C virus (HCV)-related cirrhosis. METHODS: A prospective cohort of 102 consecutive patients at their first diagnosis of CC were enrolled in this study. The clinical data and outcomes were compared to an age- and Child-Pugh class-matched cohort of 110 patients with HCV-related cirrhosis. Diagnosis of cirrhosis was based on compatible clinical and laboratory parameters, ultrasound/endoscopic parameters and, whenever possible, on histological grounds and transient elastography...
February 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28285079/defibrotide-for-patients-with-hepatic-veno-occlusive-disease-sinusoidal-obstruction-syndrome-interim-results-from-a-treatment-ind-study
#20
Paul G Richardson, Angela R Smith, Brandon M Triplett, Nancy A Kernan, Stephan A Grupp, Joseph H Antin, Leslie Lehmann, Tsiporah Shore, Massimo Iacobelli, Maja Miloslavsky, Robin Hume, Alison L Hannah, Bijan Nejadnik, Robert J Soiffer
Hepatic veno-occlusive disease, or sinusoidal obstruction syndrome (VOD/SOS), is a serious and potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) or of chemotherapy regimens alone. Defibrotide is a complex mixture of single-stranded polydeoxyribonucleotides that is approved in the United States for treating hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT and in the European Union, Israel, and South Korea for treating severe hepatic VOD/SOS post-HSCT...
March 8, 2017: Biology of Blood and Marrow Transplantation
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