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Liver transplant tolerance

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https://www.readbyqxmd.com/read/29672891/glecaprevir-pibrentasvir-treatment-in-liver-or-kidney-transplant-patients-with-hepatitis-c-virus-infection
#1
Nancy Reau, Paul Y Kwo, Susan Rhee, Robert S Brown, Kosh Agarwal, Peter Angus, Edward Gane, Jia-Horng Kao, Parvez S Mantry, David Mutimer, K Rajender Reddy, Tram T Tran, Yiran B Hu, Abhishek Gulati, Preethi Krishnan, Emily O Dumas, Ariel Porcalla, Nancy S Shulman, Wei Liu, Suvajit Samanta, Roger Trinh, Xavier Forns
Well-tolerated, ribavirin-free, pangenotypic hepatitis C virus (HCV) treatments for transplant recipients remain a high priority. Once-daily glecaprevir/pibrentasvir demonstrates high rates of sustained virologic response for 12 weeks post-treatment (SVR12) across all major HCV genotypes (GT). This trial evaluated the safety and efficacy of glecaprevir/pibrentasvir for patients with chronic HCV GT1-6 infection who had received a liver or kidney transplant. MAGELLAN-2 was a phase 3, open-label trial conducted in patients who were ≥3 months post-transplant...
April 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29670285/a-randomized-trial-of-normothermic-preservation-in-liver-transplantation
#2
David Nasralla, Constantin C Coussios, Hynek Mergental, M Zeeshan Akhtar, Andrew J Butler, Carlo D L Ceresa, Virginia Chiocchia, Susan J Dutton, Juan Carlos García-Valdecasas, Nigel Heaton, Charles Imber, Wayel Jassem, Ina Jochmans, John Karani, Simon R Knight, Peri Kocabayoglu, Massimo Malagò, Darius Mirza, Peter J Morris, Arvind Pallan, Andreas Paul, Mihai Pavel, M Thamara P R Perera, Jacques Pirenne, Reena Ravikumar, Leslie Russell, Sara Upponi, Chris J E Watson, Annemarie Weissenbacher, Rutger J Ploeg, Peter J Friend
Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29669332/paritaprevir-ritonavir-ombitasvir-plus-dasabuvir-regimen-in-the-treatment-of-genotype-1-chronic-hepatitis-c-infection-in-patients-with-severe-renal-impairment-and-end-stage-renal-disease-a-real-life-cohort
#3
Jan Sperl, Miluse Kreidlova, Dusan Merta, Klara Chmelova, Renata Senkerikova, Sona Frankova
BACKGROUND/AIMS: Chronic hepatitis C (HCV) virus infection reactivates under immunosuppressive drugs and therefore has a negative impact on long-term survival of kidney transplant recipients. Treatment-induced clearance of hepatitis C virus (HCV) in kidney transplant candidates prevents virus reactivation after transplantation. Paritaprevir/Ritonavir/Ombitasvir with Dasabuvir (PrOD) represents a highly effective treatment regimen for HCV genotype 1 (GT1), also suitable for patients with end-stage renal disease (ESRD)...
April 13, 2018: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29661427/hepatitis-c-virus-eradication-in-kidney-transplant-recipients-a-single-center-experience-in-portugal
#4
A Weigert, S Querido, L Carvalho, L Lebre, C Chagas, P Matias, R Birne, C Nascimento, C Jorge, T Adragão, M Bruges, D Machado
INTRODUCTION: Hepatitis C (HCV) is a major cause of liver impairment post-kidney transplantation (KT). Anti-HCV direct-acting antivirals (DAA) made viral eradication possible. METHODS: We performed a retrospective review of KT patients (n = 23) who received DAA at our hospital. Sustained viral response (SVR) was defined as absence of viral detection 12 weeks after cessation of therapy. RESULTS: From 1985 to September 2017, 1440 patients underwent transplantation at Hospital Santa Cruz...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29645076/the-role-of-external-beam-radiotherapy-in-the-treatment-of-hepatocellular-cancer
#5
REVIEW
Fumiko Chino, Sarah Jo Stephens, Steve S Choi, Daniele Marin, Charles Y Kim, Michael A Morse, Devon J Godfrey, Brian G Czito, Christopher G Willett, Manisha Palta
Hepatocellular carcinoma (HCC) is increasing in incidence and mortality. Although the prognosis remains poor, long-term survival has improved from 3% in 1970 to an 18% 5-year survival rate today. This is likely because of the introduction of well tolerated, oral antiviral therapies for hepatitis C. Curative options for patients with HCC are often limited by underlying liver dysfunction/cirrhosis and medical comorbidities. Less than one-third of patients are candidates for surgery, which is the current gold standard for cure...
April 12, 2018: Cancer
https://www.readbyqxmd.com/read/29644994/autoimmune-hepatitis
#6
REVIEW
Giorgina Mieli-Vergani, Diego Vergani, Albert J Czaja, Michael P Manns, Edward L Krawitt, John M Vierling, Ansgar W Lohse, Aldo J Montano-Loza
Autoimmune hepatitis (AIH) is a severe liver disease that affects children and adults worldwide. The diagnosis of AIH relies on increased serum transaminase and immunoglobulin G levels, presence of autoantibodies and interface hepatitis on liver histology. AIH arises in genetically predisposed individuals when a trigger, such as exposure to a virus, leads to a T cell-mediated autoimmune response directed against liver autoantigens; this immune response is permitted by inadequate regulatory immune control leading to a loss of tolerance...
April 12, 2018: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29643992/description-of-organ-specific-phenotype-and-functional-characteristics-of-tissue-resident-lymphocytes-from-liver-transplantation-donor-and-research-on-immune-tolerance-mechanism-of-liver
#7
Yunpeng Shi, Ping Zhang, Guangyi Wang, Xingkai Liu, Xiaodong Sun, Xin Zhang, Haijun Li, Jun Qi, Lei Ding, Ting Li, Ruoyan Zhang, Yuguo Chen, Jianpeng Zhou, Guoyue Lv, Zhengkun Tu
Aim: Prior to transplantation, Donation after Cardiac Death (DCD) liver transplantation livers are perfused with preservation solution. Therefore, this provides an abundant source of human liver lymphocytes, as well as mesenteric lymph node and spleen for the study of lymphocyte subset diversity in the peripheral blood, lymph node, spleen and liver. Methods: Lymphocyte subsets were isolated and purified from peripheral blood, lymph node, spleen and liver perfusion, the phenotypic and functional analysis of the tissue resident lymphocyte were performed by flow cytometry...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29625923/wilson-s-disease-a-2017-update
#8
Aurélia Poujois, France Woimant
Wilson's disease (WD) is characterised by a deleterious accumulation of copper in the liver and brain. It is one of those rare genetic disorders that benefits from effective and lifelong treatments that have dramatically transformed the prognosis of the disease. In Europe, its clinical prevalence is estimated at between 1.2 and 2/100,000 but the genetic prevalence is higher, at around 1/7000. Incomplete penetrance of the gene or the presence of modifier genes may account for the difference between the calculated genetic prevalence and the number of patients diagnosed with WD...
April 3, 2018: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/29623506/considerations-when-treating-hepatitis-c-in-a-cirrhotic-transplant-candidate
#9
REVIEW
Kimberly E Daniel, Adnan Said
PURPOSE OF REVIEW: This review examines the issues in determining the decision to treat a HCV-positive patient who is a liver transplant (LT) candidate with highly effective and well-tolerated direct-acting antiviral (DAA) therapies. RECENT FINDINGS: Cure of HCV with DAA can improve liver function and allow delisting in some patients. Beyond a threshold of hepatic impairment (likely MELD score > 16 to 20), patients may experience a decline in MELD score with HCV cure without improvement in liver-related complications resulting in decreased opportunity to receive a LT...
April 5, 2018: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/29619415/daclatasvir-and-sofosbuvir-treatment-of-decompensated-liver-disease-or-post-liver-transplant-hepatitis-c-virus-recurrence-in-patients-with-advanced-liver-disease-cirrhosis-in-a-real-world-cohort
#10
Paul Kwo, Michael W Fried, K Rajender Reddy, Consuelo Soldevila-Pico, Saro Khemichian, Jama Darling, Phillippe J Zamor, Andrew A Napoli, Beatrice Anduze-Faris, Robert S Brown
We report the findings of an early access program providing treatment for chronic hepatitis C virus infection (any genotype) with daclatasvir and sofosbuvir with/without ribavirin to patients with Child-Pugh class C cirrhosis or prior liver transplant recipients with recurrent hepatitis C virus infection and advanced fibrosis/cirrhosis. Patients had <12-month life expectancies per the local investigator. Patients received daclatasvir 60 mg and sofosbuvir 400 mg once daily, with/without ribavirin, for 24 weeks...
April 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29602547/ostomy-in-continuity-a-novel-approach-for-the-management-of-children-with-complex-short-bowel-syndrome
#11
Sona Sehgal, Anthony D Sandler, A Alfred Chahine, Parvati Mohan, Clarivet Torres
INTRODUCTION: Despite medical and surgical management, a subset of children with short bowel syndrome (SBS) who have discrepancy between proximal small bowel and distal colon have persistent feeding intolerance. We propose the use of an Ostomy in Continuity (OIC) (Bishop-Koop or Santulli) as a salvage procedure to decompress the proximal bowel while still maintaining maximal intestinal length, in these patients. METHODS: A retrospective chart review of 104 SBS patients identified sixteen patients who underwent an OIC...
March 4, 2018: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29599610/successful-combination-of-direct-antiviral-agents-in-liver-transplanted-patients-with-recurrent-hepatitis-c-virus
#12
Christian Rupp, Theresa Hippchen, Manuel Neuberger, Peter Sauer, Jan Pfeiffenberger, Wolfgang Stremmel, Daniel Nils Gotthardt, Arianeb Mehrabi, Karl-Heinz Weiss
AIM: To analyze the safety and efficiency of direct-acting antiviral (DAA) regimens in liver-transplanted patients with hepatitis C virus (HCV) reinfection. METHODS: Between January 2014 and December 2016, 39 patients with HCV reinfection after liver transplantation were treated at our tertiary referral center with sofosbuvir (SOF)-based regimens, including various combinations with interferon (IFN), daclatasvir (DAC), simeprivir (SIM) and/or ledipasvir (LDV). Thirteen patients were treated with SOF + IFN ± RBV...
March 28, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29579872/therapy-with-direct-acting-antiviral-agents-for-hepatitis-c-in-liver-transplant-recipients
#13
F Nogueras López, A López Garrido, E J Ortega Suazo, F Vadillo Calles, F Valverde López, M D Espinosa Aguilar
BACKGROUND: Recurrent infection with the hepatitis C virus (HCV) after liver transplantation (LT) is associated with decreased graft and patient survival. Direct-acting antiviral (DAA) therapies have changed the landscape of HCV due to their excellent safety profile and cure rates. Our aim was to evaluate the efficacy and tolerability of antiviral therapy in recurrent HCV after LT with DAA therapy. METHODS: Our retrospective analysis included 46 LT recipients with HCV recurrence...
March 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29579828/chronic-pain-treatment-with-cannabidiol-in-kidney-transplant-patients-in-uruguay
#14
L Cuñetti, L Manzo, R Peyraube, J Arnaiz, L Curi, S Orihuela
BACKGROUND: Chronic pain is a major therapeutic problem in kidney transplant patients owing to nephrotoxicity associated with nonsteroidal antiiflammatory drugs. Benefits in chronic pain treatment with cannabidiol (CBD) have been reported. This study assesses the effect, safety, and possible drug interactions in kidney transplant patients treated with CBD for chronic pain. METHODS: We assessed patients who asked to receive CBD for pain treatment. Doses were increased from 50 to 150 mg twice a day for 3 weeks...
March 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29575875/assessment-of-the-efficacy-of-ofatumumab-in-patients-with-chronic-lymphocytic-leukaemia-treated-in-the-department-of-haematooncology-and-bone-marrow-transplantation-of-the-medical-university-in-lublin-prelimary-results
#15
Ewa Wąsik-Szczepanek, Agnieszka Szymczyk, Małgorzata Kowal, Adam Nogalski, Marek Hus
INTRODUCTION: Despite significant recent advances in the treatment of chronic lymphocytic leukaemia (CLL), most cases of the disease are still incurable. Treatment with monoclonal antibodies, such as ofatumumab, is one of the new therapeutic options. OBJECTIVE: Retrospective analysis of the efficacy of ofatumumab in patients with chronic lymphocytic leukaemia (CLL) treated in the Haematooncology and Bone Marrow Transplantation Department of the Medical University of Lublin, Poland, during 2011-2013...
March 14, 2018: Annals of Agricultural and Environmental Medicine: AAEM
https://www.readbyqxmd.com/read/29572391/infusion-of-donor-derived-cd8-memory-t-cells-for-relapse-following-allogeneic-hematopoietic-cell-transplantation
#16
Lori Muffly, Kevin Sheehan, Randall Armstrong, Kent Jensen, Keri Tate, Andrew R Rezvani, David Miklos, Sally Arai, Judith Shizuru, Laura Johnston, Everett Meyer, Wen-Kai Weng, Ginna G Laport, Robert S Negrin, Sam Strober, Robert Lowsky
Murine models showed that CD8+ CD44hi memory T (TM ) cells could eradicate malignant cells without inducing graft-versus-host disease (GVHD). We evaluated the feasibility and safety of infusing freshly isolated and purified donor-derived phenotypic CD8+ TM cells into adults with disease relapse after allogeneic hematopoietic cell transplantation (HCT). Phenotypic CD8 TM cells were isolated after unmobilized donor apheresis using a tandem immunomagnetic selection strategy of CD45RA depletion followed by CD8+ enrichment...
March 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29569736/safety-and-efficacy-of-ledipasvir-sofosbuvir-with-or-without-ribavirin-in-hepatitis-c-genotype-1-patients-including-those-with-decompensated-cirrhosis-who-failed-prior-treatment-with-simeprevir-sofosbuvir
#17
A A Modi, H E Nazario, G R Gonzales, S A Gonzalez
BACKGROUND: Combination therapy of simeprevir (SIM)/sofosbuvir (SOF) is an approved treatment for hepatitis C genotype (gen) 1 with overall SVR12 rate of 85%-95%. The single tablet fixed-dose combination of ledipasvir (LDV)/SOF is also approved for gen 1 with sustained virologic response at 12 weeks (SVR12) rates ≥95%. No data are available on the efficacy of retreatment with LDV/SOF in patients who failed initial treatment with SIM/SOF. AIM: Our aim was to evaluate the efficacy of retreatment with LDV/SOF ± ribavirin (RBV) in gen 1 patients who had previously failed treatment with SIM/SOF...
March 23, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29545802/potential-beneficial-effects-of-cytomegalovirus-infection-after-transplantation
#18
REVIEW
Nicolle H R Litjens, Lotte van der Wagen, Jurgen Kuball, Jaap Kwekkeboom
Cytomegalovirus (CMV) infection can cause significant complications after transplantation, but recent emerging data suggest that CMV may paradoxically also exert beneficial effects in two specific allogeneic transplant settings. These potential benefits have been underappreciated and are therefore highlighted in this review. First, after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) using T-cell and natural killer (NK) cell-replete grafts, CMV reactivation is associated with protection from leukemic relapse...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29545795/serial-monitoring-of-immune-markers-being-represented-regulatory-t-cell-t-helper-17-cell-ratio-indicating-tolerance-for-tapering-immunosuppression-after-liver-transplantation
#19
JooYeon Jhun, Seung Hoon Lee, Soon Kyu Lee, Hee Yeon Kim, Eun Sun Jung, Dong Goo Kim, JeongWon Choi, Si Hyun Bae, Seung Kew Yoon, Byung Ha Chung, Chul Woo Yang, Mi-La Cho, Jong Young Choi
Recipients of liver transplantation (LT) require long-term immunosuppressive drug treatment, but lifelong immunosuppressive treatment has severe side effects. It is known that some LT recipients develop immune tolerance, and although the development of such operational tolerance should allow a decrease in the burden of immunosuppressive drug treatment, the factors that indicate operational tolerance are not clear. This study aimed to monitor immunological markers over time in LT recipients to identify those markers indicating the development of operational tolerance...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29535728/cell-therapy-in-organ-transplantation-our-experience-on-the-clinical-translation-of-regulatory-t-cells
#20
REVIEW
Niloufar Safinia, Nathali Grageda, Cristiano Scottà, Sarah Thirkell, Laura J Fry, Trishan Vaikunthanathan, Robert I Lechler, Giovanna Lombardi
Solid organ transplantation is the treatment of choice for patients with end-stage organ dysfunction. Despite improvements in short-term outcome, long-term outcome is suboptimal due to the increased morbidity and mortality associated with the toxicity of immunosuppressive regimens and chronic rejection (1-5). As such, the attention of the transplant community has focused on the development of novel therapeutic strategies to achieve allograft tolerance, a state whereby the immune system of the recipient can be re-educated to accept the allograft, averting the need for long-term immunosuppression...
2018: Frontiers in Immunology
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