Cell-mediated rejection results in allograft loss after liver cell transplantation

Abstract

Liver cell transplantation in humans has been impeded by invariable loss of the graft. It is unclear whether graft loss is due to an immune response against donor hepatocytes. Transplantation with ABO-matched liver cells was performed in a patient with Crigler-Najjar type 1. After successful engraftment, there was a gradual loss of graft function. Solid-phase enzyme immunoassay testing and cell-complement cytotoxicity assays detecting preformed antibodies directed toward class I and/or class II human leukocyte antigen (HLA) molecules were negative. In contrast, a striking host alloresponse to either the HLA-B39 or C7 antigen was found, suggesting that a vigorous response to a defined mismatched HLA antigen contributed to graft loss in our patient. This study provides evidence that a T-cell-mediated immune mechanism could be responsible for human liver cell transplant graft loss. This finding warrants confirmation in future liver cell transplants in humans. Liver Transpl 14:688-694, 2008.

De Novo Donor-Specific HLA Antibody Formation in Two Patients With Crigler-Najjar Syndrome Type I Following Human Hepatocyte Transplantation With Partial Hepatectomy Preconditioning

“…Hepatocytes have tolerogenic properties, and initially it was believed that immunosuppressive therapy might not be necessary 19; however, Allen et al reported a cellular alloresponse directed against donor class I HLA associated with hepatocyte graft loss 19. No DSAs were detected in this patient.…”

In Vitro Evaluation of Magnetic Resonance Imaging Contrast Agents for Labeling Human Liver Cells: Implications for Clinical Translation

“…Liver cell transplantation (LCT) was developed to enable treatment of multiple patients with cells obtained from one donor organ and to provide alternatives in cases with contraindications for major surgery, i.e., LTx [1,2]. While initial clinical studies demonstrated the safety and efficacy of LCT, success remained limited since LCT could not achieve the outcomes required for it to be established as a standard medical treatment [3,4]. As part of further clinical studies on improvement of LCT, strategies for non-invasive monitoring of transplanted cells are under investigation [5][6][7].…”

Clinical Hepatocyte Transplantation: Practical Limits and Possible Solutions

“…No general consensus exists regarding the optimal immunosuppressive protocol following HTx. Many centers simply adopt the same protocol used for OLT, consisting of steroid induction and calcineurin inhibitors (tacrolimus or cyclosporine) [3,5,11,14,20,23,25,55,111]. Immunosuppressive regimens without steroids or with low doses of calcineurin inhibitors have been recommended, particularly in patients affected by urea cycle disorders, because of their catabolic effects [58].…”

“…HTx has been proven as an effective therapy for a number of acute and chronic diseases, including acute liver failure, cirrhosis, and metabolic liver disease [2,3,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29], with documented improvements in the relevant clinical parameters after the procedure. HTx can be used not only to prolong and improve the quality of life in patients listed for OLT but also as a long-term stand-alone treatment, since it can provide support for metabolic and synthetic liver functions while the native liver regenerates and provide enzyme activity/functions in patients with metabolic liver disease.…”