title: Combined liver-total bowel transplantation has no immunologic advantage over total bowel transplantation alone. A prospective study in a porcine model.
abstract: BACKGROUND
  Rejection remains a major obstacle to successful bowel transplantation in humans. It has been suggested that a simultaneous liver transplant would shield the bowel graft from immunologic attack, but the liver shortage would be aggravated. In a preclinical model, we studied the influence of simultaneous liver grafting by comparing the incidence of early bowel rejection after combined liver-total (small- and large-) bowel transplants vs total bowel transplants alone.
  
  
  METHODS
  We assessed the incidence of early post-transplant rejection, graft-vs-host disease, and infection after combined liver-total bowel transplants (group 1, n = 10) and total bowel transplants alone (group 2, n = 9) in outbred Yorkshire Landrace pigs. Liver and bowel grafts were transplanted orthotopically with portal vein drainage after recipient hepatectomy (group 1) and total enterectomy (groups 1 and 2). Posttransplant immunosuppression was performed with intravenous tacrolimus (whole blood levels, 15 to 30 ng/mL) and prednisolone. In groups 1 and 2, bowel biopsy specimens from the ileostomy were obtained daily. In group 1, liver biopsy specimens were obtained weekly. Rejection was graded according to a 4-point scoring system (none, mild, moderate, and severe).
  
  
  RESULTS
  Overall graft survival at days 7, 14, and 21 was 89%, 44%, and 11%, respectively, in group 1 vs 100%, 100%, and 86%, respectively, in group 2 (P < .001). Death rates owing to (irreversible) rejection at days 7, 14, and 21 were 0% in groups 1 and 2 (P = .48). Grading of bowel rejection episodes, based on the results of daily biopsy specimens, was not significantly different between the groups whether on individual days or overall. In group 1, the incidence of liver rejection episodes was as high as 66% (day 14 and at autopsy). At autopsy, generalized graft-vs-host disease (skin, native intestine, and native liver) was noted in 55% of group 1 and 43% of group 2 pigs (P = .55). Graft-vs-host disease was noted concurrently with rejection episodes of the liver or bowel grafts.
  
  
  CONCLUSIONS
  Simultaneous liver grafting did not further reduce the incidence of early bowel rejection or graft-vs-host disease when compared with total bowel transplants alone. Based on the results of this preclinical study, simultaneous liver grafting is not indicated for patients with short-bowel syndrome and normal liver function.
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Gruessner
authors.forename: R E
authors.initials: RE
authors.lastname: Nakhleh
authors.forename: E
authors.initials: E
authors.lastname: Benedetti
authors.forename: J
authors.initials: J
authors.lastname: Pirenne
authors.forename: K G
authors.initials: KG
authors.lastname: Belani
authors.forename: D
authors.initials: D
authors.lastname: Beebe
authors.forename: R
authors.initials: R
authors.lastname: Carr
authors.forename: C
authors.initials: C
authors.lastname: Troppmann
authors.forename: A C
authors.initials: AC
authors.lastname: Gruessner
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000453:epidemiology*; D015994:Incidence; D007422:Intestines / Q000473:pathology / Q000637:transplantation*; D016031:Liver Transplantation / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D013552:Swine