title: De Novo Donor-Specific HLA Antibody Formation in Two Patients With Crigler-Najjar Syndrome Type I Following Human Hepatocyte Transplantation With Partial Hepatectomy Preconditioning.
abstract: Clinical hepatocyte transplantation is hampered by low engraftment rates and gradual loss of function resulting in incomplete correction of the underlying disease. Preconditioning with partial hepatectomy improves engraftment in animal studies. Our aim was to study safety and efficacy of partial hepatectomy preconditioning in clinical hepatocyte transplantation. Two patients with Crigler-Najjar syndrome type I underwent liver resection followed by hepatocyte transplantation. A transient increase of hepatocyte growth factor was seen, suggesting that this procedure provides a regenerative stimulus. Serum bilirubin was decreased by 50%, and presence of bilirubin glucuronides in bile confirmed graft function in both cases; however, graft function was lost due to discontinuation of immunosuppressive therapy in one patient. In the other patient, serum bilirubin gradually increased to pretransplant concentrations after ≈600 days. In both cases, loss of graft function was temporally associated with emergence of human leukocyte antigen donor-specific antibodies (DSAs). In conclusion, partial hepatectomy in combination with hepatocyte transplantation was safe and induced a robust release of hepatocyte growth factor, but its efficacy on hepatocyte engraftment needs to be evaluated with additional studies. To our knowledge, this study provides the first description of de novo DSAs after hepatocyte transplantation associated with graft loss.
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Jorns
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Nowak
authors.affiliation: Division of Pediatrics, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Nemeth
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Zemack
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: L-M
authors.initials: LM
authors.lastname: Mörk
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Johansson
authors.affiliation: Department of Laboratory Medicine, Division of Pathology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Gramignoli
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Karadagi
authors.affiliation: Division of Clinical Immunology and Transfusion, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Alheim
authors.affiliation: Division of Clinical Immunology and Transfusion, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Hauzenberger
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van Dijk
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Bosma
authors.affiliation: Department of Pediatrics, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Ebbesen
authors.affiliation: Department of Laboratory Medicine, Division of Pathology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Szakos
authors.affiliation: Division of Pediatrics, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Fischler
authors.affiliation: Department of Laboratory Medicine, Division of Pathology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Strom
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Ellis
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: B-G
authors.initials: BG
authors.lastname: Ericzon
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation / Q000276:immunology*; D002648:Child; D003414:Crigler-Najjar Syndrome / Q000276:immunology* / Q000601:surgery; D005260:Female; D006084:Graft Rejection / Q000209:etiology*; D006680:HLA Antigens / Q000276:immunology*; D006498:Hepatectomy / Q000009:adverse effects*; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D007223:Infant; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D011183:Postoperative Complications; D011379:Prognosis; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens
keywords: cellular transplantation (non-islet); immune regulation; liver (native) function/dysfunction; liver disease: congenital; liver transplantation/hepatology; regenerative medicine; translational research/science