Bile Duct Strictures after Liver Transplantation are Associated with a Donor Glypican-6 Polymorphism Linked to the Biliary Stem Cell Niche
J.W. Selten, F.J.M. Roos, C.J. Verhoeven, H.J. Metselaar, J.N.M Ijzermans, L.J.W. van der Laan
Chair(s): Dr. B.G. Hepkema
Thursday 9 march 2017
12:30 - 12:45h
Categories: Poster - Basaal
Parallel session: Postersessie - Basaal 1
Introduction:
bile duct strictures (ischemia type biliary lesions and anastomotic strictures) are one of the most common complications after liver transplantation, with an incidence of approximately 30%. The origin of these strictures seems multi-factorial, but damage to bile duct stem cell niche is found to play an important role. Glypican-6 (GPC-6) has recently been identified as an stem cell niche factor important for stimulation of the Wnt-signaling pathway and linked to primary sclerosing cholangitis (PSC). However, the role of GPC-6 in bile duct strictures post transplantation has not been established.
Methods:
a retrospective PCR-based SNP analysis was performed for GPC-6 status of liver donors and recipients transplanted between 1989 and 2010. PSC recipients were excluded from analysis.
Results:
overall, GPC-6 status could be identified in 309 recipients, 241 donors and 201 paired donor-recipient combinations. Of the 309 transplantation recipients, biliary strictures occurred in 87 grafts (37.2%). Distribution of the GPC-6 polymorphism did not differ between the recipient (AA (n=40) vs AG/GG (n=269)) and donor (AA (n=40) vs AG/GG (n=201)) (p = 0.818). Donor GPC-6 AA genotype was associated with the development of biliary strictures (p = 0.024). Multivariate analysis with other known risk factors for bile duct strictures showed GPC-6 AA genotype as an independent risk factor for biliary strictures (p=0.050).
Conclusions:
donor GPC-6 AA genotype is an independent risk factor for the development of bile duct strictures after liver transplantation in non-PSC recipients. The exact relationship of GPC-6 and bile duct injury may be based on decreased Wnt-activation of epithelial stem cells in the peribiliary glands or other stem cell niches. Investigation of the role of GPC-6 genotypes in Wnt-activation is currently on going in organoid cultures of biliary stem cells.
