title: Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures.
abstract: OBJECTIVE
  The peribiliary glands of large bile ducts have been identified as a niche of progenitor cells that contribute to regeneration of biliary epithelium after injury. We aimed to determine whether injury to the peribiliary glands of donor livers is a risk factor for development of non-anastomotic biliary strictures (NAS) after liver transplantation.
  
  
  METHODS
  In 128 liver transplant procedures, biopsies were taken from the donor bile duct and injury was assessed using an established histological grading system. Histological severity of injury was subsequently compared in liver grafts that later developed biliary structures vs. uncomplicated liver grafts.
  
  
  RESULTS
  Luminal biliary epithelial loss >50% was observed in 91.8% of the grafts before transplantation, yet NAS occurred in only 16.4%. Periluminal peribiliary glands were more severely injured than deep peribiliary glands located near the fibromuscular layer (>50% loss in 56.9% vs. 17.5%, respectively; p<0.001). Injury of deep peribiliary glands was more prevalent and more severe in livers that later developed NAS, compared to grafts without NAS (>50% loss in 50.0% vs. 9.8%, respectively; p=0.004). In parallel, injury of the peribiliary vascular plexus was more severe in livers that developed NAS, compared to grafts without NAS (>50% vascular changes in 57.1% vs. 20.3%; p=0.006).
  
  
  CONCLUSIONS
  Injury of peribiliary glands and vascular plexus before transplantation is strongly associated with the occurrence of biliary strictures after transplantation. This suggests that insufficient regeneration due to loss of peribiliary glands or impaired blood supply may explain the development of biliary strictures.
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Sanna
authors.initials: S
authors.lastname: op den Dries
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Andrie C
authors.initials: AC
authors.lastname: Westerkamp
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Negin
authors.initials: N
authors.lastname: Karimian
authors.affiliation: Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Annette S H
authors.initials: AS
authors.lastname: Gouw
authors.affiliation: Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, Boston, MA, United States.
authors.forename: Bote G
authors.initials: BG
authors.lastname: Bruinsma
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Ton
authors.initials: T
authors.lastname: Lisman
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Heidi
authors.initials: H
authors.lastname: Yeh
authors.affiliation: Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, Boston, MA, United States.
authors.forename: Korkut
authors.initials: K
authors.lastname: Uygun
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Paulo N
authors.initials: PN
authors.lastname: Martins
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: r.j.porte@umcg.nl.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Porte
mesh_terms: D000328:Adult; D017734:Bile Ducts, Extrahepatic / Q000293:injuries* / Q000473:pathology*; D002779:Cholestasis / Q000209:etiology* / Q000473:pathology; D004848:Epithelium / Q000473:pathology / Q000502:physiology; D005260:Female; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007511:Ischemia / Q000209:etiology / Q000473:pathology; D008102:Liver Circulation; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012038:Regeneration / Q000502:physiology; D055153:Stem Cell Niche; D014019:Tissue Donors
keywords: Bile duct injury; Biliary complications; Donation after cardiac death; Ischemic cholangiopathy; Ischemic type biliary injury; Liver transplantation; Non-anastomotic biliary strictures; Regeneration