Liver Transplant Immunology 1: Fundamentals of Liver Immunology and Allorecognition

2018 ◽  
Author(s):  
Michael Kriss ◽  
Hugo Rosen

The liver is a multifunctional organ responsible for complex metabolic and immune functions. Although not a classic lymphoid organ, the liver is enriched with traditional immune cells as well as parenchymal and nonparenchymal cells that play a key role in immune homeostasis. Due to its location and unique anatomic structure, the liver must finely balance immunity and tolerance to avoid undue inflammation in the setting of constant antigenic exposure from portal blood flow while maintaining appropriate immunity against pathogens. Since the first successful liver transplantation in humans in 1967 at the University of Colorado, our knowledge of hepatic immunity and tolerance, in the context of both liver disease and liver transplantation, has evolved dramatically. With these advancements, therapeutic modalities have been developed that have revolutionized the care of liver transplant recipients. In Part 1: Fundamentals of Liver Immunology and Allorecognition, we review current knowledge of hepatic immunity, including anatomic features and cellular components that give the liver its unique properties. In addition, we describe critical concepts of innate and adaptive immune function to provide a context for understanding allograft injury and rejection. This review contains 4 figures, 4 tables and 26 references. Key Words: adaptive immunity; allorecognition; antigen presenting cells; innate immunity; liver transplantation; T lymphocytes

2018 ◽  
Author(s):  
Michael Kriss ◽  
Hugo Rosen

The liver is a multifunctional organ responsible for complex metabolic and immune functions. Although not a classic lymphoid organ, the liver is enriched with traditional immune cells as well as parenchymal and nonparenchymal cells that play a key role in immune homeostasis. Due to its location and unique anatomic structure, the liver must finely balance immunity and tolerance to avoid undue inflammation in the setting of constant antigenic exposure from portal blood flow while maintaining appropriate immunity against pathogens. Since the first successful liver transplantation in humans in 1967 at the University of Colorado, our knowledge of hepatic immunity and tolerance, in the context of both liver disease and liver transplantation, has evolved dramatically. With these advancements, therapeutic modalities have been developed that have revolutionized the care of liver transplant recipients.  In Part 2: Application to Liver Allograft Immunity, we apply the basic principles of liver immunology and allorecognition to our current management of liver transplant recipients in the context of both immunosuppression and the holy grail of transplantation, operational tolerance. This review contains 4 figures, 3 tables, and 32 references Key Words: adaptive immunity; allograft rejection; allograft tolerance; allorecognition; antigen presenting cells; immunosuppression; innate immunity; liver transplantation; T lymphocytes


2021 ◽  
Vol 8 ◽  
pp. 205435812110297
Author(s):  
Jean Maxime Côté ◽  
Isabelle Ethier ◽  
Héloïse Cardinal ◽  
Marie-Noëlle Pépin

Background: Chronic kidney disease following liver transplantation is a major long-term complication. Most liver transplant recipients with kidney failure will be treated with dialysis instead of kidney transplantation due to noneligibility and shortage in organ availability. In this population, the role of peritoneal dialysis (PD) as a modality of kidney replacement therapy (KRT) remains unclear. Objective: To determine the feasibility regarding safety, technique survival, and dialysis efficiency of PD in liver transplant recipients requiring KRT for maintenance dialysis. Design: Systematic review. Setting: Interventional and observational studies reporting the use of PD after liver transplantation. Patients: Adult liver transplant recipients with kidney failure treated with maintenance KRT. Measurements: Extracted data included eligibility criteria, study design, demographics, and PD modality. The following outcomes of interest were extracted: rate of peritonitis and microorganisms involved, noninfectious peritoneal complications, technique survival, and kidney transplantation-censored technique survival. Non-PD complications included overall survival, liver graft dysfunction, and hospitalization rate. Methods: The following databases were searched until July 2020: MedLine/PubMed, EMBASE, CINAHL, and Cochrane Library. Two reviewers independently screening all titles and abstracts of all identified articles. Due to the limited sample size, observational designs and study heterogeneity expected, no meta-analysis was pre-planned. Descriptive statistics were used to report all results. Results: From the 5263 identified studies, 4 were included in the analysis as they reported at least 1 outcome of interest on a total of 21 liver transplant recipients, with an overall follow-up duration on PD of 19.0 (Interquartile range [IQR]: 9.5-29.5) months. Fifteen episodes of peritonitis occurred in a total cumulative PD follow-up of 514 patient-months, representing an incidence rate of 0.35 per year. These episodes did not result in PD technique failure, mortality, or impairment of liver graft function. Limitations: Limitations include the paucity of studies in the field and the small number of patients included in each report, a risk of publication bias and the impossibility to directly compare hemodialysis to PD in this population. These results, therefore, must be interpreted with caution. Conclusions: Based on limited data reporting the feasibility of PD in liver transplant recipients with kidney failure, no signal was associated with an increased risk of infectious complications. Long-term studies evaluating this modality need to be performed. Registration (PROSPERO): CRD42020218374.


2021 ◽  
Vol 22 (4) ◽  
pp. 2213
Author(s):  
Natalia Diaz-Garrido ◽  
Cecilia Cordero ◽  
Yenifer Olivo-Martinez ◽  
Josefa Badia ◽  
Laura Baldomà

Communication between cells is crucial to preserve body homeostasis and health. Tightly controlled intercellular dialog is particularly relevant in the gut, where cells of the intestinal mucosa are constantly exposed to millions of microbes that have great impact on intestinal homeostasis by controlling barrier and immune functions. Recent knowledge involves extracellular vesicles (EVs) as mediators of such communication by transferring messenger bioactive molecules including proteins, lipids, and miRNAs between cells and tissues. The specific functions of EVs principally depend on the internal cargo, which upon delivery to target cells trigger signal events that modulate cellular functions. The vesicular cargo is greatly influenced by genetic, pathological, and environmental factors. This finding provides the basis for investigating potential clinical applications of EVs as therapeutic targets or diagnostic biomarkers. Here, we review current knowledge on the biogenesis and cargo composition of EVs in general terms. We then focus the attention to EVs released by cells of the intestinal mucosa and their impact on intestinal homeostasis in health and disease. We specifically highlight their role on epithelial barrier integrity, wound healing of epithelial cells, immunity, and microbiota shaping. Microbiota-derived EVs are not reviewed here.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M G Abdelrahman ◽  
H A Mahmoud ◽  
M K Mohsen ◽  
M O Ali ◽  
A M N Mohamed

Abstract Background Liver transplantation is considered to be the only curative treatment for patients with end stage liver disease. Postoperative infection remains to be one of the most common causes of morbidity and mortality throughout the past years. Cytomegalovirus (CMV) infection although considered to be a weak viral infection that usually passes asymptomatic in immunocompetent patients, however, it is considered one of the most common pathogens causing morbidities and mortality in liver transplant recipients. Multiple studies have been done to assess the risk factors for developing CMV infection. Objective Identification of risk factors predicting Cytomegalovirus infection in liver transplant recipients following transplantation. Methods This retrospective study was conducted on 194 patients and their donors who underwent living donor liver transplantation operation at Ain Shams centre for organ transplantation (ASCOT) at Ain Shams specialized hospital in the period between January 2010 and December 2016 with at least one year follow up period after operation for the recipient group. Results In our study, 194 patients undergoing liver transplantation at Ain shams centre for organ transplantation over seven years from January 2010 to December 2016 have been followed to assess risk factors affecting CMV infection development. Chronic rejection was found to be the most common factor associated with CMV infection followed by Cyclosporin (Neoral) as main postoperative immunosuppressant following liver transplantation. Other factors that were found to carry risk for CMV infection included younger age, advanced MELD score, positive CMV IgM status of the donors and recipients. Conclusion Differentiation of Cytomegalovirus disease from Cytomegalovirus infection isn’t always available as it requires tissue invasive techniques. Multiple risk factors have been attributed to cause Cytomegalovirus infection (viremia) . In our study, rejection (chronic rejection) was the factor that carries highest risk for Cytomegalovirus infection development followed by Cyclosporin .


2014 ◽  
Vol 25 (3) ◽  
pp. 159-162 ◽  
Author(s):  
Clara Tan-Tam ◽  
Pamela Liao ◽  
Julio S Montaner ◽  
Mark W Hull ◽  
Charles H Scudamore ◽  
...  

BACKGROUND: The demand for definitive management of end-stage organ disease in HIV-infected Canadians is growing. Until recently, despite international evidence of good clinical outcomes, HIV-infected Canadians with end-stage liver disease were ineligible for transplantation, except in British Columbia (BC), where the liver transplant program of BC Transplant has accepted these patients for referral, assessment, listing and provision of liver allograft. There is a need to evaluate the experience in BC to determine the issues surrounding liver transplantation in HIV-infected patients.METHODS: The present study was a chart review of 28 HIV-infected patients who were referred to BC Transplant for liver transplantation between 2004 and 2013. Data regarding HIV and liver disease status, initial transplant assessment and clinical outcomes were collected.RESULTS: Most patients were BC residents and were assessed by the multidisciplinary team at the BC clinic. The majority had undetectable HIV viral loads, were receiving antiretroviral treatments and were infected with hepatitis C virus (n=16). The most common comorbidities were anxiety and mood disorders (n=4), and hemophilia (n=4). Of the patients eligible for transplantation, four were transplanted for autoimmune hepatitis (5.67 years post-transplant), nonalcoholic steatohepatitis (2.33 years), hepatitis C virus (2.25 years) and hepatitis B-delta virus coinfection (recent transplant). One patient died from acute renal failure while waiting for transplantation. Ten patients died during preassessment and 10 were unsuitable transplant candidates. The most common reason for unsuitability was stable disease not requiring transplantation (n=4).CONCLUSIONS: To date, interdisciplinary care and careful selection of patients have resulted in successful outcomes including the longest living HIV-infected post-liver transplant recipient in Canada.


The Lancet ◽  
2000 ◽  
Vol 356 (9230) ◽  
pp. 621-627 ◽  
Author(s):  
René Adam ◽  
Valérie Cailliez ◽  
Pietro Majno ◽  
Vincent Karam ◽  
Paul McMaster ◽  
...  

Surgery Today ◽  
1994 ◽  
Vol 24 (7) ◽  
pp. 621-626 ◽  
Author(s):  
Kazuhiro Tsukada ◽  
Takeo Sakaguchi ◽  
Takemi Tomiyama ◽  
Katsuyuki Uchida ◽  
Yoshinobu Sato ◽  
...  

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