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Liver transplant tolerance

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https://www.readbyqxmd.com/read/28217256/interferon-free-regimens-in-patients-with-hepatitis-c-infection-and-renal-dysfunction-or-kidney-transplantation
#1
REVIEW
Evangelos Cholongitas, Chrysoula Pipili, George V Papatheodoridis
Treatment of patients with chronic kidney disease (CKD) and chronic hepatitis C (CHC) differs from that used in the general CHC population mostly when glomerular filtration rate (GFR) is below 30 mL/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile...
February 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28207637/the-efficacy-of-a-prevascularized-retrievable-poly-d-l-lactide-co-%C3%AE%C2%B5-caprolactone-subcutaneous-scaffold-as-transplantation-site-for-pancreatic-islets
#2
Alexandra M Smink, Shiri Li, Don T Hertsig, Bart J de Haan, Leendert Schwab, Aart A van Apeldoorn, Eelco de Koning, Marijke M Faas, Jonathan R T Lakey, Paul de Vos
BACKGROUND: The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) (PDLLCL) scaffold...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28199304/adipose-derived-circulating-mirnas-regulate-gene-expression-in-other-tissues
#3
Thomas Thomou, Marcelo A Mori, Jonathan M Dreyfuss, Masahiro Konishi, Masaji Sakaguchi, Christian Wolfrum, Tata Nageswara Rao, Jonathon N Winnay, Ruben Garcia-Martin, Steven K Grinspoon, Phillip Gorden, C Ronald Kahn
Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue-brown especially-into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21...
February 23, 2017: Nature
https://www.readbyqxmd.com/read/28187014/delayed-donor-bone-marrow-infusion-induces-liver-transplant-tolerance
#4
Yan Xie, Yang Wu, Kang Xin, Jiao-Jing Wang, Hong Xu, Suzanne T Ildstad, Joseph Leventhal, Guang-Yu Yang, Zheng Zhang, Josh Levitsky
BACKGROUND: Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications. METHODS: Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls...
February 10, 2017: Transplantation
https://www.readbyqxmd.com/read/28178174/real-world-experience-with-interferon-free-direct-acting-antiviral-therapies-in-asian-americans-with-chronic-hepatitis-c-and-advanced-liver-disease
#5
Christine Y Chang, Pauline Nguyen, An Le, Changqing Zhao, Aijaz Ahmed, Tami Daugherty, Gabriel Garcia, Glen Lutchman, Radhika Kumari, Mindie H Nguyen
Real-life data on interferon (IFN)-free direct acting antiviral (DAA) therapies for chronic hepatitis C (CHC) is limited for Asian Americans.To evaluate sustained virologic response (SVR) and adverse events (AE) in Asian Americans treated with sofosbuvir (SOF)-based, IFN-free DAA therapies.This is a retrospective study of 110 consecutive Asian Americans with HCV genotypes 1 to 3 or 6 treated with IFN-free SOF-based regimens for 8 to 24 weeks between February 2014 and March 2016 at a university center in Northern California...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28178089/hepatitis-c-virus-therapy-for-decompensated-and-posttransplant-patients
#6
Francis Dailey, Walid S Ayoub
Treatment of hepatitis C (HCV) has been revolutionized with the introduction of the direct-acting antivirals (DAA). The DAAs allowed patients to better tolerate HCV therapy with much lower side effects and better efficacy. The DAA also offered hope for a cure in HCV patients who cannot tolerate interferon-based therapy. Such populations include patients with decompensated cirrhosis and postliver transplantation. Despite DAA therapy showing cure rate of over 95% in the absence of cirrhosis, cure rate in the decompensated liver disease setting remains lower...
March 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28177199/daclatasvir-plus-sofosbuvir-with-or-without-ribavirin-for-hepatitis-c-virus-genotype-3-in-a-french-early-access-programme
#7
Christophe Hézode, Pascal Lebray, Victor De Ledinghen, Fabien Zoulim, Vincent Di Martino, Nathalie Boyer, Dominique Larrey, Danielle Botta-Fridlund, Christine Silvain, Hélène Fontaine, Louis D'Alteroche, Vincent Leroy, Marc Bourliere, Isabelle Hubert-Fouchard, Dominique Guyader, Isabelle Rosa, Eric Nguyen-Khac, Larysa Fedchuk, Raoudha Akremi, Yacia Bennai, Anne Filipovics, Yue Zhao, Jean-Pierre Bronowicki
BACKGROUND AND AIMS: Optimally effective treatment for hepatitis C virus (HCV) genotype 3 (GT3) is urgently needed, particularly in advanced liver disease. Daclatasvir (DCV) plus sofosbuvir (SOF) was efficacious in phase 3 studies. Real-world data for DCV+SOF in advanced GT3 infection are presented from the French Temporary Authorisation for Use programme, which allowed patients in need without other treatment options access to DCV ahead of its market authorization. METHODS: Patients with F3/F4 fibrosis and/or extrahepatic HCV manifestations, post-liver-transplant HCV recurrence, and/or indication for liver/kidney transplant, were treated with DCV+SOF (60+400 mg daily) for a recommended duration of 24 weeks...
February 8, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28170112/treatment-of-hepatitis-c-virus-infection-in-patients-with-cirrhosis-and-predictive-value-of-meld-analysis-of-data-from-the-hepa-c-registry
#8
Carlos Fernández Carrillo, Sabela Lens, Elba Llop, Juan Manuel Pascasio, Javier Crespo, Juan Arenas, Inmaculada Fernández, Carme Baliellas, José Antonio Carrión, Manuel de la Mata, Maria Buti, Lluís Castells, Agustín Albillos, Manuel Romero, Juan Turnes, Clara Pons, José María Moreno-Planas, José Javier Moreno-Palomares, Conrado Fernández-Rodriguez, Javier García-Samaniego, Martín Prieto, Miguel Fernández Bermejo, Javier Salmerón, Ester Badia, Magdalena Salcedo, José Ignacio Herrero, Rafael Granados, Michel Blé, Zoe Mariño, José Luis Calleja
Direct-acting antiviral agents (DAAs) are highly effective and well tolerated in patients with chronic hepatitis C virus (HCV) infection, including those with compensated cirrhosis. However, fewer data are available in patients with more advanced liver disease. Our retrospective, non-interventional, national, multi-center study in patients from the Spanish Hepa-C registry investigated the effectiveness and safety of interferon-free DAA regimens in patients with advanced liver disease, including those with decompensated cirrhosis, in routine practice (all currently approved regimens were registered)...
February 7, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28162154/-the-effect-of-semimature-dendritic-cell-and-the-levels-of-treg-on-transplantation-tolerance-of-hepatocytes-differentiated-from-mouse-embryonic-stem-cell
#9
C Zhang, W W Liao, B Cai, F R Liu, Q Ke, X F Zhu, X S He, A B Hu
Objective: To investigate the inducing effect and mechanism of semimature dendritic cell (smDCs) on transplantation tolerance of hepatocytes differentiated from mouse embryonic stem cells (ESCs), and to study the connections between smDCs and regulatory dendritic cells (regDCs). Methods: ESCs of 129 mouse labelled green fluorescent protein (GFP) were induced to hepatocytes by using previous methods. Meanwhile, bone marrow mononuclear cells of 129 mouse were induced to smDCs and regDCs. Moreover, the hepatocytes differentiated from 129 mouse ESCs were transplanted into liver of BALB/c mouse 3 days after infusing smDCs and regDCs suspension of 129 mouse into BALB/c mouse by tail vein respectively...
January 24, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28138756/treatment-with-sofosbuvir-and-ledipasvir-without-ribavirin-for-12%C3%A2-weeks-is-highly-effective-for-recurrent-hepatitis-c-virus-genotype-1b-infection-after-living-donor-liver-transplantation-a-japanese-multicenter-experience
#10
Yoshihide Ueda, Toru Ikegami, Nobuhisa Akamatsu, Akihiko Soyama, Masahiro Shinoda, Ryoichi Goto, Hideaki Okajima, Tomoharu Yoshizumi, Akinobu Taketomi, Yuko Kitagawa, Susumu Eguchi, Norihiro Kokudo, Shinji Uemoto, Yoshihiko Maehara
BACKGROUND: The optimal therapy for recurrent hepatitis C virus (HCV) infection after liver transplantation has not yet been established. This study aimed to clarify the efficacy and safety of interferon-free therapy with sofosbuvir and ledipasvir without ribavirin for 12 weeks in Japanese patients with HCV genotype 1b infection after living donor liver transplantation. METHODS: A cohort study of living donor liver transplant recipients with recurrent HCV genotype 1b infection treated with sofosbuvir (400 mg/day) and ledipasvir (90 mg/day) was performed at six liver transplant centers in Japan...
January 30, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28104136/acute-calcineurin-inhibitor-nephrotoxicity-secondary-to-turmeric-intake-a-case-report
#11
A Nayeri, S Wu, E Adams, C Tanner, J Meshman, I Saini, W Reid
Tacrolimus, also known as FK-506, is a potent immunosuppressant agent with a host of drug-drug and food-drug interactions. We present the first case of a probable food-drug interaction between the herb turmeric and tacrolimus leading to acute calcineurin inhibitor nephrotoxicity. A 56-year-old man with a history of orthotopic liver transplantation presented to the emergency department from the clinic with worsening edema in the setting of an elevated creatinine level of 4.2 mg/dL. Before the current presentation, the patient had been recently discharged on a previously tolerated low-dose regimen of tacrolimus with a whole-blood tacrolimus level within the desired range...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28101345/%C3%AE-cell-function-prior-to-liver-transplantation-contributes-to-post-operative-diabetes
#12
Tatsuki Ichikawa, Naota Taura, Hisamitsu Miyaaki, Satoshi Miuma, Hidetaka Shibata, Takuya Honda, Masaaki Hidaka, Akihiko Soyama, Mitsuhisa Takatsuki, Susumu Eguchi, Kazuhiko Nakao
Liver cirrhosis and diabetes mellitus (DM) are closely associated. The present study aimed to determine whether liver transplantation (LT) may prevent/cure DM in patients with cirrhosis and whether the degree of glucose tolerance prior to transplantation is associated with the onset of DM after transplantation. Seventy-three patients who received a living donor LT at Nagasaki University Hospital (Nagasaki, Japan) between November 2005 and December 2012 were recruited. Among them, patients were considered diabetic if they had been prescribed diabetes medications or had impaired glucose tolerance, as evidenced by an oral glucose tolerance test (OGTT)...
December 2016: Biomedical Reports
https://www.readbyqxmd.com/read/28051797/%C3%A2-sofosbuvir-and-daclatasvir-in-mono-and-hiv-coinfected-patients-with-recurrent-hepatitis-c-after-liver-transplant
#13
Lluís Castells, Jordi Llaneras, Isabel Campos-Varela, Itxarone Bilbao, Manel Crespo, Oscar Len, Francisco Rodríguez-Frías, Ramon Charco, Teresa Salcedo, Juan Ignacio Esteban, Rafael Esteban-Mur
:  Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. MATERIAL AND METHODS: We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program...
January 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28041666/prediabetes-in-pediatric-recipients-of-liver-transplant-mechanism-and-risk-factors
#14
Emily R Perito, Robert H Lustig, Philip Rosenthal
OBJECTIVE: To investigate the role of calcineurin inhibitor exposure and states of insulin resistance-obesity and adolescence-in prediabetes after pediatric liver transplant via oral glucose tolerance testing, which previously has not been done systematically in these at-risk youths. STUDY DESIGN: This was a cross-sectional study of 81 pediatric recipients of liver transplant. Prediabetes was defined as impaired glucose tolerance (IGT; glucose ≥140 mg/dL at 2 hours) or impaired fasting glucose (IFG, ≥100 mg/dL)...
March 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28039929/epstein-barr-virus-dna-monitoring-in-serum-and-whole-blood-in-pediatric-liver-transplant-recipients-who-do-or-do-not-discontinue-immunosuppressive-therapy
#15
C Kullberg-Lindh, R Saalman, M Olausson, G Herlenius, M Lindh
The rate of PTLD can be reduced by weaned IS guided by monitoring of EBV DNA. In this single-center retrospective case series study, we analyzed how reduction in IS influenced EBV DNA levels in whole blood and serum in 30 children during the first year after liver transplantation, and how these levels were related to symptoms putatively due to EBV. Primary and reactivated EBV infection was seen in 18 (60%) and eight patients (27%), respectively. Thirteen patients (42%) developed chronic high load the first year post-transplant...
December 31, 2016: Pediatric Transplantation
https://www.readbyqxmd.com/read/28027587/analysis-of-surgical-interruption-of-the-enterohepatic-circulation-as-a-treatment-for-pediatric-cholestasis
#16
Kasper S Wang, Greg Tiao, Lee M Bass, Paula M Hertel, Douglas Mogul, Nanda Kerkar, Matthew Clifton, Colleen Azen, Laura Bull, Philip Rosenthal, Dylan Stewart, Riccardo Superina, Ronen Arnon, Molly Bozic, Mary L Brandt, Patrick A Dillon, Annie Fecteau, Kishore Iyer, Binita Kamath, Saul Karpen, Frederick Karrer, Kathleen M Loomes, Cara Mack, Peter Mattei, Alexander Miethke, Kyle Soltys, Yumirle P Turmelle, Karen West, Jessica Zagory, Cat Goodhue, Benjamin L Shneider
: To evaluate the efficacy of non-transplant surgery for pediatric cholestasis, 58 clinically diagnosed children, including 20 Alagille syndrome (ALGS), 16 Familial Intrahepatic Cholestasis-1 (FIC1), 18 Bile Salt Export Pump (BSEP) disease, & 4 others with low γ-glutamyl transpeptidase disease (levels <100 U/L), were identified across 14 Childhood Liver Disease Research Network (ChiLDReN) centers. Data were collected retrospectively from individuals who collectively had 39 partial external biliary diversions (PEBD), 11 ileal exclusions (IE) and 7 gallbladder-to-colon diversion (GBC)...
December 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28024124/developing-therapies-to-treat-hepatitis-c-infection-in-post-liver-transplant-recipients
#17
Thomas R McCarty, Joseph K Lim
Currently, hepatitis C virus (HCV) infection remains the most common indication for liver transplant in the United States (US) with almost universal HCV recurrence in the post-liver transplant setting. Previous interferon (IFN)-related efficacy and tolerability concerns about worsening liver function have limited treatment options for many patients with HCV-associated decompensated liver disease and post-liver transplant recipients. However, the last decade has seen a seen a radical shift in the management of HCV with multiple direct-acting antiviral (DAA) treatments that provide more effective, all-oral, IFN-free alternatives...
February 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28012215/real-world-experience-with-daclatasvir-plus-sofosbuvir-%C3%A2-ribavirin-for-post-liver-transplant-hcv-recurrence-and-severe-liver-disease
#18
Kerstin Herzer, Tania M Welzel, Ulrich Spengler, Holger Hinrichsen, Hartwig Klinker, Thomas Berg, Peter Ferenci, Markus Peck-Radosavljevic, Akin Inderson, Yue Zhao, Maria Jesus Jimenez-Exposito, Stefan Zeuzem
Optimizing therapy of post-transplant HCV recurrence remains important, especially in advanced liver disease. We evaluated daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in patients with post-liver transplant recurrence in a real-world European cohort at high risk of decompensation or death within 12 months. Recommended treatment was DCV 60mg plus SOF 400mg once-daily for 24 weeks; RBV use/shorter treatment duration was at physicians' discretion. Patients (N=87) were 70% male, 93% white, and mostly infected with HCV genotypes 1b (48%), 1a (32%), or 3 (9%); 37 (43%) had cirrhosis (16 decompensated), five had fibrosing cholestatic hepatitis...
December 24, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28006874/sofosbuvir-ledipasvir-and-ribavirin-tolerability-and-efficacy-in-pediatric-liver-transplant-recipients
#19
Koen Huysentruyt, Xavier Stephenne, Sharat Varma, Isabelle Scheers, Gisèle Leclercq, Françoise Smets, Etienne Sokal
No abstract text is available yet for this article.
December 22, 2016: Liver Transplantation
https://www.readbyqxmd.com/read/28006867/differential-profile-of-activated-regulatory-t-cell-subsets-and-micrornas-in-tolerant-liver-transplant-recipients
#20
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
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