Basics and Art of Immunosuppression in Liver Transplantation

Poudel, Shekhar; Gupta, Subhash; Saigal, Sanjiv

doi:10.1016/j.jceh.2024.101345

Cited by 3 publications

(1 citation statement)

References 119 publications

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“…Within this overarching challenge, solid organ and VCA transplantation are emerging as particularly critical concerns. Solid organ transplantation faces distinct challenges related to organ compatibility, ischemia-reperfusion injury, and the imperative for lifelong immunosuppression [32][33][34]. Similarly, VCA transplantation introduces additional complexities due to the unique requisites of VCA organs, such as the face, hands, or uterus, and the inherent risk of rejection [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Engraftment and Safety of Human Umbilical Di-Chimeric Cell (HUDC) Therapy after Systemic Intraosseous Administration in an Experimental Model

Siemionow,

Chambily,

Brodowska

2024

Biomedicines

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Cell-based therapies hold promise for novel therapeutic strategies in regenerative medicine. We previously characterized in vitro human umbilical di-chimeric cells (HUDCs) created via the ex vivo fusion of human umbilical cord blood (UCB) cells derived from two unrelated donors. In this in vivo study, we assessed HUDC safety and biodistribution in the NOD SCID mouse model at 90 days following the systemic intraosseous administration of HUDCs. Twelve NOD SCID mice (n = 6/group) received intraosseous injection of donor UCB cells (3.0 × 106) in Group 1, or HUDCs (3.0 × 106) in Group 2, without immunosuppression. Flow cytometry assessed hematopoietic cell surface markers in peripheral blood and the presence of HLA-ABC class I antigens in lymphoid and non-lymphoid organs. HUDC safety was assessed by weekly evaluations, magnetic resonance imaging (MRI), and at autopsy for tumorigenicity. At 90 days after intraosseous cell administration, the comparable expression of HLA-ABC class I antigens in selected organs was found in UCB control and HUDC therapy groups. MRI and autopsy confirmed safety by no signs of tumor growth. This study confirmed HUDC biodistribution to selected lymphoid organs following intraosseous administration, without immunosuppression. These data introduce HUDCs as a novel promising approach for immunomodulation in transplantation.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Engraftment and Safety of Human Umbilical Di-Chimeric Cell (HUDC) Therapy after Systemic Intraosseous Administration in an Experimental Model

Siemionow,

Chambily,

Brodowska

2024

Biomedicines

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RhD‐negative red blood cells can be saved during liver transplantation in RhD‐negative patients due to low risk of alloimmunization against RhD

Juhl,

Braun,

Brockmann

et al. 2024

Transfusion

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BackgroundTransfusion demand is high in liver transplantation (LT), and thus RhD‐positive (RhD+) red blood cell concentrates (RBCs) are sometimes given to RhD‐negative (RhD‐) patients. Due to immunosuppression, these patients rarely produce anti‐D. We investigated the rate of anti‐D formation in RhD‐ patients undergoing LT who were transfused with RhD+ RBCs as well as the number of transfused RhD‐ and RhD+ RBCs.Study Design and MethodsRhD‐type and transfusion history of all patients undergoing LT between 2010 and 2023 were reviewed retrospectively. In RhD‐ patients, who received RhD+ RBCs, the results of antibody screening test (indirect antiglobulin test and with papain‐treated test cells) and direct antiglobulin test were evaluated.ResultsFive hundred and twenty‐seven patients underwent 576 LT. Eighty‐seven patients were RhD‐, of whom 42 were transfused with RhD+ RBCs. In 34 of them, an antibody screening test result was available more than two weeks after the last RhD+ RBCs transfusion. In two of them, a transient, weak anti‐D antibody was detectable, which disappeared in the further course. Overall, 1352 RBCs were transfused to the 87 RhD‐ patients, 543 of those were RhD+. Most RhD+ RBCs were provided to men and elder women.DiscussionTransient weak anti‐D occurred in two RhD‐ male patients during LT after transfusion of RhD+ RBCs without evidence for a hemolytic transfusion reaction. To save stocks of RhD‐ RBCs, early transfusion of RhD+ RBCs to RhD‐ men and women beyond the childbearing age should be considered during LT.

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Post-transplant complications in alcohol- and metabolic-associated steatotic liver disease

Jadaun,

Saigal

2024

Metab Target Organ Damage

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Alcohol-associated liver disease (ALD) and metabolic-associated steatotic liver disease (MASLD)/metabolic-associated steatohepatitis (MASH) are severe liver diseases, with liver transplant being the primary curative treatment option. Transplant recipients with ALD suffer from alcohol use disorder (AUD) and poor drug compliance, which can result in graft injury and even graft loss. Relapse of alcohol consumption, lack of drug compliance, and smoking negatively impact the graft and clinical outcome of ALD-related transplantation patients. Furthermore, these patients are at a higher risk of developing non-hepatic complications such as malignancies, cardiovascular diseases, and other metabolic conditions. The management of these conditions requires pharmacological and behavioral strategies to manage complications as soon as they arise. Critical monitoring of these conditions is also advocated. In patients undergoing transplants for MASLD/MASH, early complications arise in obese and diabetic patients. Late post-transplant complications such as cardiovascular diseases, chronic kidney disease, recurring MASLD/MASH, immunosuppression, and arterial hypertension are reported. Integrating behavioral strategies with diet modification and physical activity is crucial to balance underlying metabolic disorders and improve clinical outcomes. Early steroid withdrawal and low calcineurin inhibitor doses can decrease the risk of post-transplant diabetes, hypertension, and dyslipidemia. Lifestyle modifications and tailored immunosuppression are helpful in the prevention and management of post-transplant recurrent MASLD/MASH.

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Basics and Art of Immunosuppression in Liver Transplantation

Cited by 3 publications

References 119 publications

Efficacy of Engraftment and Safety of Human Umbilical Di-Chimeric Cell (HUDC) Therapy after Systemic Intraosseous Administration in an Experimental Model

Efficacy of Engraftment and Safety of Human Umbilical Di-Chimeric Cell (HUDC) Therapy after Systemic Intraosseous Administration in an Experimental Model

RhD‐negative red blood cells can be saved during liver transplantation in RhD‐negative patients due to low risk of alloimmunization against RhD

Post-transplant complications in alcohol- and metabolic-associated steatotic liver disease

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