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Polymorphism and liver transplant

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https://www.readbyqxmd.com/read/28945950/complexity-and-function-of-nkt-cells-with-potential-application-to-hepatic-transplant-survival
#1
REVIEW
Randle Ware, Vipin Kumar
One of the major innate-like lymphocyte populations enriched in liver consists of Natural Killer T (NKT) cells, which recognize self and foreign lipid antigens presented by the non-polymorphic class I MHC-like molecule CD1d. NKT cells express NK cell markers as well as T cell receptors (TCR) and can be classified into 2 categories: type I NKT cells use a semi-invariant TCR whereas type II NKT cells express diverse but still limited TCRs. An emerging body of evidence points to their opposing roles in inflammation, including ischemic reperfusion injury...
September 25, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28941036/association-of-donor-sumo4-rs237025-genetic-variant-with-tacrolimus-elimination-in-the-early-period-after-liver-transplantation
#2
Tao Zhang, Yuan Liu, Rong Zeng, Qi Ling, Peihao Wen, Junwei Fan, Zhihai Peng
BACKGROUNDS & AIMS: Individualized tacrolimus treatment can improve drug safety and efficacy. In this study, we aimed to investigate the association of donor and recipient small ubiquitin-like modifier 4 (SUMO4) rs237025 polymorphisms with tacrolimus elimination and the potential mechanism. METHODS: A total of 297 liver transplant patients were enrolled in the study. CYP3A5 rs776746 and SUMO4 rs237025 were genotyped using TaqMan SNPs assays. The activity of nuclear factor-kB (NF-kB) was evaluated by luciferase assay...
September 21, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28922436/genetic-risk-factors-for-autoimmune-thyroid-disease-might-affect-the-susceptibility-to-and-modulate-the-progression-of-primary-biliary-cholangitis
#3
Aleksander Kuś, Magdalena Arłukowicz-Grabowska, Konrad Szymański, Ewa Wunsch, Małgorzata Milkiewicz, Rafał Płoski, Zakera Shums, Gary L Norman, Piotr Milkiewicz, Tomasz Bednarczuk, Marcin Krawczyk
BACKGROUND AND AIMS: Patients with primary biliary cholangitis (PBC) frequently suffer from extrahepatic autoimmune conditions, of which autoimmune thyroid disease (AITD) is one of the most common. Previous studies identified several genetic variants increasing the odds of developing AITD. Here we investigate whether AITD-associated polymorphisms might also play a role in the development and clinical course of PBC and PBC associated with AITD (PBC-AITD). METHODS: To this end, we prospectively recruited 230 patients with PBC and 421 healthy controls...
September 2017: Journal of Gastrointestinal and Liver Diseases: JGLD
https://www.readbyqxmd.com/read/28857712/a-novel-drug-interaction-between-busulfan-and-blinatumomab
#4
Karen Sweiss, John G Quigley, Annie Oh, Jonathan Lee, Rosa Ye, Damiano Rondelli, Pritesh Patel
Busulfan is an alkylating agent used in pre-transplant conditioning for patients undergoing hematopoietic stem cell transplantation. Several factors contribute to variations in busulfan drug disposition including bioavailability, age, liver function, genetic polymorphisms, and concurrent administration of other drugs. Busulfan is metabolized by hepatic oxidation via the cytochrome P450 3A4 system as well as through conjugation with glutathione. Interactions with drugs such as phenytoin, itraconazole, and metronidazole have been reported to alter busulfan clearance and result in sub- or supra-therapeutic concentrations...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28833329/population-pharmacokinetics-and-bayesian-estimation-of-tacrolimus-exposure-in-chinese-liver-transplant-patients
#5
B Chen, H-Q Shi, X-X Liu, W-X Zhang, J-Q Lu, B-M Xu, H Chen
WHAT IS KNOWN AND OBJECTIVES: Tacrolimus (TAC) is widely used as part of immunosuppressive regimens. There is great interindividual variation on the disposition of TAC. The aim of this study was to develop a population pharmacokinetic (PPK) model for Chinese liver transplant patients and evaluate genetic polymorphism and other possible factors on the PK parameters. The exposure of TAC is to be estimated through Bayesian modelling. METHODS: A total of 47 sets of rich-time PK and 1234 conventional therapeutic drug monitoring (TDM) data were collected from 125 Chinese liver transplant patients...
August 17, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28718984/effect-of-pnpla3-i148m-polymorphism-on-histologically-proven-nonalcoholic-fatty-liver-disease-in-liver-transplant-recipients
#6
Hyeyoung Kim, Kwang-Woong Lee, Kyoungbun Lee, Sooin Seo, Min-Young Park, Sung Woo Ahn, Suk Kyun Hong, Kyung Chul Yoon, Hyo-Sin Kim, YoungRok Choi, Hae Won Lee, Nam-Joon Yi, Kyung-Suk Suh
AIM: PNPLA3 I148M polymorphism (rs738409 C>G) is the most important and the best known polymorphism for nonalcoholic fatty liver disease (NAFLD). However, little is known about the effect of this polymorphism on NAFLD after liver transplantation (LT). We aimed to evaluate the association between this polymorphism and post-LT NAFLD. METHODS: We designed a prospective case-control study. Among adult recipients who underwent LT between April 2014 and October 2015, those whose whole blood were preoperatively collected for genotyping in both recipients and coupled donors and those who have undergone protocol biopsy at post-LT 1 year were enrolled...
July 18, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28705752/polymorphisms-of-the-human-platelet-antigen-1-2-3-5-and-15-systems-and-acute-cellular-liver-transplant-rejection
#7
Hansjörg Thude, Wiebke Bischoff, Martina Sterneck, Matthias Marget, Björn Nashan, Martina Koch
The human platelet antigen (HPA)-1, -2, -3, -5, and -15 systems are characterized as polymorphic alloantigens expressed on platelets and endothelial cells. In this retrospective study, we investigated, whether HPA-1, -2, -3, -5, and -15 incompatibilities are associated with acute cellular liver transplant rejection. A total of 96 Caucasian liver transplant recipients and corresponding donors were analyzed, 43 with biopsy proven acute cellular rejection (BPAR) and 53 without acute cellular rejection (No-BPAR)...
July 10, 2017: Human Immunology
https://www.readbyqxmd.com/read/28689037/association-of-donor-and-recipient-sumo4-rs237025-genetic-variant-with-new-onset-diabetes-mellitus-after-liver-transplantation-in-a-chinese-population
#8
Tao Zhang, Yuan Liu, Yibo Hu, Xiaoqing Zhang, Lin Zhong, Junwei Fan, Zhihai Peng
BACKGROUNDS & AIMS: New-onset diabetes mellitus (NODM) is a common complication after liver transplantation (LT). The small ubiquitin-like modifier 4 (SUMO4) rs237025 polymorphism has been reported to be associated with type 2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the association of donor and recipient SUMO4 rs237025 polymorphisms with NODM and the long-term consequences of NODM after LT. METHODS: A total of 126 liver transplant patients were enrolled in the study...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28685716/gene-variations-of-sixth-complement-component-affecting-tacrolimus-metabolism-in-patients-with-liver-transplantation-for-hepatocellular-carcinoma
#9
Jian-Hua Liao, Chang-Can Li, Shao-Han Wu, Jun-Wei Fan, Hai-Tao Gu, Zhao-Wen Wang
BACKGROUND: Orthotopic liver transplantation (OLT) improves the prognosis of patients with hepatocellular carcinoma (HCC). Moreover, the complement system is a powerful immune effector that can affect liver function and process of liver cirrhosis. However, studies correlating the complement system with tacrolimus metabolism after OLT are scarce. In this study, the role of single nucleotide polymorphisms (SNPs) associated with the sixth complement component (C6) in tacrolimus metabolism was investigated during the early stages of liver transplantation...
July 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28676024/nafld-nash-an-under-recognized-epidemic
#10
Joseph Jennings, Charles Faselis, Michael D Yao
First described in 1980, nonalcoholic fatty liver disease (NAFLD) has become more common although the exact incidence and prevalence is unknown. While the exact prevalence varies from region to region, the overall trend shows an increased number of patients with NAFLD. Risk factors for the development of NAFLD includes advanced age, male gender, obesity, and having elements of the metabolic syndrome. There is also an association between the presence of NAFLD and coronary atherosclerosis. Persons of Hispanic descent tend to have higher rates of NAFLD when compared with other populations...
June 20, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28649744/mannose-binding-lectin-deficient-donors-increase-the-risk-of-bacterial-infection-and-bacterial-infection-related-mortality-after-liver-transplantation
#11
J Lombardo-Quezada, G Sanclemente, J Colmenero, M Español-Rego, M T Arias, P Ruiz, E Mauro, L Sastre, G Crespo, A Rimola, A Moreno, F Lozano, M Navasa
Mannose-binding lectin (MBL) is synthesized by the liver and binds to microbes. MBL2 gene polymorphisms produce intermediate/low/null or normal MBL serum levels (MBL-deficient or MBL-sufficient phenotypes, respectively). We aimed to evaluate the incidence and severity of infection, rejection, and survival within 1 year after liver transplantation (LT) according to donor and recipient MBL2 gene polymorphisms. A repeated-event analysis for infection episodes (negative binomial regression, Andersen-Gill model) was performed in 240 LTs...
June 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28640108/correlation-of-hla-dp-dq-polymorphisms-with-transplant-etiologies-and-prognosis-in-liver-transplant-recipients
#12
Yi Li, Qian Huang, Jiang-Tao Tang, Tian-Tian Wei, Lin Yan, Zhi-Qiang Yang, Yang-Juan Bai, Lan-Lan Wang, Yun-Ying Shi
Previous study has identified that the genetic variants in the human leukocyte antigen (HLA)-DP/DQ region were strongly associated with hepatitis B virus (HBV) infection. But their roles in liver function recovery after hepatic transplantation were still obscure. This study aimed to investigate whether HLA-DP/DQ polymorphisms were associated with post-transplant etiologies and prognosis in Chinese liver transplant recipients.A total of 144 liver transplant recipients were enrolled, which were divided into 2 groups according to the transplant etiology: HBV-related disease and non-HBV-related disease...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28624888/steady-state-pharmacokinetics-of-mycophenolic-acid-in-renal-transplant-patients-exploratory-analysis-of-the-effects-of-cyclosporine-recipients-and-donors-abcc2-gene-variants-and-their-interactions
#13
N Božina, Z Lalić, S Nađ-Škegro, A Borić-Bilušić, T Božina, Ž Kaštelan, V Trkulja
PURPOSE: The study aims to evaluate the impact of recipients' and donors' polymorphisms in multidrug resistance-associated protein 2 (MRP2) gene ABCC2 -24C>T and 1249G>A on disposition of mycophenolic acid (MPA) and their interaction with cyclosporine (CsA) (compared to tacrolimus, TAC) in stable de novo adult renal transplant patients of Croatian origin. METHODS: A total of 68 recipient-donor pairs were genotyped. Steady-state pharmacokinetics of MPA was assessed by the model-independent method...
September 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28620648/effect-of-fc-%C3%AE-receptor-polymorphism-on-rituximab-mediated-b-cell-depletion-in-abo-incompatible-adult-living-donor-liver-transplantation
#14
Hiroshi Sakai, Yuka Tanaka, Hirofumi Tazawa, Seiichi Shimizu, Sapana Verma, Masahiro Ohira, Hiroyuki Tahara, Kentaro Ide, Kohei Ishiyama, Tsuyoshi Kobayashi, Takashi Onoe, Hideki Ohdan
BACKGROUND: The affinity of IgG Fc receptor (FcγR) for rituximab, an anti-CD20 IgG1, differs based on single-nucleotide polymorphisms (SNPs) in FcγRs. This study aimed to explore the effect of such SNPs on clinical response to rituximab and outcomes in patients of ABO-incompatible (ABOi) living donor liver transplantation (LDLT). METHODS: SNPs of FCGR2A[131H/R] and FCGR3A[158F/V], alleles encoding FcγR, were identified in 20 patients desensitized with rituximab before ABOi LDLT...
June 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28604474/impact-of-cyp2c19-genotype-and-liver-function-on-voriconazole-pharmacokinetics-in-renal-transplant-recipients
#15
Zi-Wei Li, Feng-Hua Peng, Miao Yan, Wu Liang, Xiao-Lei Liu, Yan-Qin Wu, Xiao-Bin Lin, Sheng-Lan Tan, Feng Wang, Ping Xu, Ping-Fei Fang, Yi-Ping Liu, Da-Xiong Xiang, Bi-Kui Zhang
BACKGROUND: Invasive fungal infection (IFI) is one of the leading causes of early death after renal transplantation. Voriconazole (VRC) is the first-line drug of IFI. Because of the large inter- and intraindividual variability in VRC plasma concentrations and the narrow therapeutic window for treating patients with IFIs, it is crucial to study the factors which could influence pharmacokinetic variability. We performed a population pharmacokinetics (PPK) study of VRC for personalized medicine...
August 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28585914/glutathione-s-transferase-gene-polymorphisms-and-the-development-of-new-onset-diabetes-after-liver-transplant
#16
Zahra Musavi, Elham Moasser, Neda Zareei, Negar Azarpira, Ali Shamsaeefar
OBJECTIVES: The association between the glutathione S-transferase polymorphisms and the development of new-onset diabetes mellitus after liver transplant was studied. MATERIALS AND METHODS: Peripheral blood samples were collected from 106 liver transplant patients divided into 2 groups: 52 with new-onset diabetes mellitus and 54 without new-onset diabetes mellitus; 169 healthy individuals with no clinical evidence of diabetes mellitus were selected as a control group...
June 5, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28574625/patatin-like-phospholipase-domain-containing-3-gene-as-a-liver-steatosis-risk-factor-following-living-donor-liver-transplantation-for-hepatitis-c
#17
Hisamitsu Miyaaki, Satoshi Miuma, Naota Taura, Hidetaka Shibata, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Susumu Eguchi, Kazuhiko Nakao
Liver steatosis frequently occurs following liver transplantation (LT) and can affect patient outcome. Here, we aimed to clarify the steatosis and steatohepatitis risk factors that apply after living-donor LT for chronic hepatitis C.We retrospectively examined 43 transplant recipients and donors, and tested for single-nucleotide polymorphisms in the patatin-like phospholipase domain-containing 3 gene (PNPLA3). Liver biopsies taken 1 year after transplantation and yearly thereafter, or when abnormal liver enzyme levels were detected, were examined by histopathology...
June 2, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28441386/graft-derived-cell-free-dna-a-noninvasive-early-rejection-and-graft-damage-marker-in-liver-transplantation-a-prospective-observational-multicenter-cohort-study
#18
MULTICENTER STUDY
Ekkehard Schütz, Anna Fischer, Julia Beck, Markus Harden, Martina Koch, Tilo Wuensch, Martin Stockmann, Björn Nashan, Otto Kollmar, Johannes Matthaei, Philipp Kanzow, Philip D Walson, Jürgen Brockmöller, Michael Oellerich
BACKGROUND: Graft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, is a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional liver function tests (LTFs) nor immunosuppressive drug monitoring are very effective for rejection monitoring. We therefore hypothesized that the quantitative measurement of donor-derived cell-free DNA (cfDNA) would have independent value for the assessment of graft integrity, including damage from acute rejection...
April 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28411360/association-between-tlr2-tlr4-and-cd14-gene-polymorphisms-and-acute-rejection-in-kidney-transplant
#19
Razieh Abdolvahabi, Abdolfatah Sarrafnejad, Mohsen Nafar, Davood Jafari, Efat Razaghi, Mahboob Lessan-Pezashki, Mir Saeed Yekaninejad, Ehsan Sharif-Paghaleh, Aliakbar Amirzargar
OBJECTIVES: Toll-like receptors play an important role in innate and adaptive immune responses and can induce acute graft rejection, especially in the early phase after transplant. The aim of this study was to evaluate the possible association between TLR2, TLR4, and CD14 polymorphisms and acute renal rejection. MATERIALS AND METHODS: Our study included 239 patients seen between 2013 and 2015. Patients were classified into 3 groups: acute rejection group (71 patients), stable graft function group (71 patients), and healthy control group (97 patients)...
April 14, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28403123/influence-of-genetic-variations-in-the-sod1-gene-on-the-development-of-ascites-and-spontaneous-bacterial-peritonitis-in-decompensated-liver-cirrhosis
#20
Sebastian Schwab, Jennifer Lehmann, Philipp Lutz, Christian Jansen, Beate Appenrodt, Frank Lammert, Christian P Strassburg, Ulrich Spengler, Hans-Dieter Nischalke, Jonel Trebicka
BACKGROUND: The balance between generation and elimination of reactive oxygen species by superoxide dismutase (SOD) is crucially involved in the pathophysiology of liver cirrhosis. Reactive oxygen species damage cells and induce inflammation/fibrosis, but also play a critical role in immune defense from pathogens. As both processes are involved in the development of liver cirrhosis and its complications, genetic variation of the SOD1 gene was investigated. PATIENTS AND METHODS: Two SOD1 single nucleotide polymorphisms (rs1041740 and rs3844942) were analyzed in 49 cirrhotic patients undergoing liver transplantation...
July 2017: European Journal of Gastroenterology & Hepatology
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