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The Host Response to Grafts and Transplantation Immunology
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The immunosuppressive regimes in use to prevent acute rejection have little or no effect on chronic rejection. Currently, there are no satisfactory methods available to control chronic rejection. Because of this, the gradual rate of graft loss due to chronic rejection has not changed over the years. This is illustrated in Figure 11.2.
Lung transplantation
Published in Claudio F. Donner, Nicolino Ambrosino, Roger S. Goldstein, Pulmonary Rehabilitation, 2020
Chronic rejection is a widespread problem that frequently occurs in the long-term post-transplant phase in these patients (73). It is diagnosed based on a worsening of expiratory flow limitation and results in increased symptoms of dyspnoea and reductions in functional exercise capacity and QOL (64,73). Referring these patients to a supervised outpatient rehab programme might be a viable treatment option to improve symptoms and daily functioning. This has, however, not been formally studied so far.
Pathology of the Intrahepatic Biliary Tree after Liver Transplantation
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
James Neuberger, Rebecca Harrison
Some help in the understanding of the pathogenesis of chronic rejection may come from knowledge of the risk factors for chronic rejection. Overall, the strongest risk factor for chronic rejection is a previous graft that has developed chronic rejection. In the first allograft, our own study14 suggested that risk factors included a male liver grafted into a female patient; in this scenario, we postulated that there might be an immune reaction against the HY antigen, expressed on the ‘male’ liver; this is analogous to the situation in bone marrow transplantation. Of interest, it has been suggested that the biliary epithelial cells express estrogen receptors and, in vitro at least, blockade of these receptors blocks proliferation and triggers apoptosis of Fas positive biliary epithelial cells.15 The relevance to the in vivo situation is unknown.
Cancer Risks in Solid Organ Transplant Recipients: Results from a Comprehensive Analysis of 72 Cohort Studies
Published in OncoImmunology, 2020
Zhenyu Huo, Caichen Li, Xin Xu, Fan Ge, Runchen Wang, Yaokai Wen, Haoxin Peng, Xiangrong Wu, Hengrui Liang, Guilin Peng, Run Li, Danxia Huang, Ying Chen, Ran Zhong, Bo Cheng, Shan Xiong, Weiyi Lin, Jianxing He, Wenhua Liang
We also found that liver cancer risk was most elevated in liver transplant recipients among solid organ transplant recipients. Liver cancer is the most common complication in end-stage liver disease patients, and liver transplantation can be an ideal therapy for patients with localized liver cancer .102 Possible reasons to explain the elevated liver cancer risk include the relapse of infection of HBV and HCV, diabetes mellitus, and the delate recognition of liver cancer in the donor liver.56 Due to the significant organ specificity, we speculate the elevated liver cancer risk may also be related to the chronic rejection reaction after liver transplantation. Also, the incidence of ulcerative colitis after liver transplantation was increased, which could result in the elevated colorectal cancer risk in post-liver transplant recipients55 .103
Development of transplant immunosuppressive agents – considerations in the use of animal models
Published in Expert Opinion on Drug Discovery, 2018
Russell Costello, Adrien Kissenpfennig, Paulo N Martins, James McDaid
Another target for costimulation blockade is the CD40-CD40L (CD154) interaction, CD40L present on the surface of the T cell binds to CD40 on APCs; this interaction seems to activate the APC rather than the T cell. Humanized antibody targeting CD154 has demonstrated reasonable efficacy in prolonging graft survival in primate models [87]. Anti-CD154 has prolonged the survival times of renal, islet, heart and skin grafts in primate models. If used as monotherapy on a maintenance regimen of monthly infusions, transplant survival of up five years may be seen. However, the graft may still experience changes associated with chronic rejection. The dosage of anti-CD154 is higher than typically seen with other antibody therapies. This may be due to the expression of CD40L on cells such as platelets rather than T cells alone. There has been some debate as to whether costimulation blockade therapeutics such as anti-CD154 are compatible with conventional immunosuppressant treatments, but there is evidence to suggest that they are, and human studies have been suspended for idiosyncratic thrombotic events, which could perhaps have been predicted from primate experiments [88]. Targeting CD40 has so far been less effective than targeting of CD40L. This may be because the anti-CD40 binds less avidly or perhaps CD40L has other functions alongside binding CD40 [68].
Hepatocyte Differentiation from iPSCs or MSCs in Decellularized Liver Scaffold: Cell–ECM Adhesion, Spatial Distribution, and Hepatocyte Maturation Profile
Published in Organogenesis, 2022
Radiana Dhewayani Antarianto, Adrian Pragiwaksana, Wahyunia Likhayati Septiana, Nuzli Fahdia Mazfufah, Ameer Mahmood
Liver transplantation is the mainstream medical therapy for patients with end-stage liver disease.1 Significant restriction in liver transplantation is the limited number of available and suitable living liver donors. Liver transplant failure could be due to acute or chronic rejection. Standard post-transplant regiment to overcome rejection is the long-term use of immunosuppressive drugs. This increases the risk of severe viral or fungal infection in addition to malignancy. In brief, hepatocyte replacement therapy uses isolated hepatocytes of liver resected from a relative. They are expanded in vitro before being infused to the patient. This procedure has been shown to reduce immunosuppressive drug use and related complication.2