Fucosyltransferase-2 Non-Secretor Status Is Associated With Non-Anastomotic Biliary Strictures After Liver Transplantation in Recipients With Primary Sclerosing Cholangitis.

Intestinal Bacteremia After Liver Transplantation Is a Risk Factor for Recurrence of Primary Sclerosing Cholangitis

“…Our data are consistent and supported by recent literature that showed that nonsecretor status is strongly associated with adverse outcomes in patients with PSC and UC, including overall mortality and death from sepsis supports our data. 22–24 Not only do the results of our study confirm the pathophysiological role of bacteremia and altered glycosylation in PSC as identified by previous studies; it is also the first study that shows that the FUT2 genotype is an independent risk factor for transplant outcome following LT.…”

“…[45][46][47][48] Remarkably, the correlation between FUT2 dysfunction and UC is less clear, with contradictory results in various studies. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] In the current study, we observed a higher frequency of FUT2 nonsecretors in LT recipients also suffering from UC, compared with recipients with CD or without IBD. This suggests that rPSC is a consequence of intestinal barrier defects that also affects the intestine and the intestinal microbiome and is not an intrinsic liver-originating phenotype.…”

“…45–48 Remarkably, the correlation between FUT2 dysfunction and UC is less clear, with contradictory results in various studies. 8–26…”

“…20,21 In particular, a mutation in the fucosyltransferase-2 (FUT2) gene accelerates the disease course of PSC and reduces the transplantation-free survival of these patients. 22,23 The wild type allele of the FUT2 gene contains a G at position 48703417 of chr. 19 (human reference genome version GRCh38), while an A at the same position results in a mutated (truncated and nonfunctional) allele.…”

“…These so-called FUT2 nonsecretors have a perturbed composition of the cellular glycocalyx and are, therefore, less resistant against the passage of bacteria and other pathogens through the intestinal epithelium to extraintestinal sites like the liver and bile ducts via the portal vein. 23,25 In addition, an FUT2 nonsecretor status has an effect on both the composition and function of the colonic microbiota, leading to an increased risk of biliary infections in PSC patients. [26][27][28] Due to a predisposition for bacterial translocation in FUT2 nonsecretors and the link between PSC and FUT2 SNPs, we hypothesized that patients with underlying PSC are prone to develop PSC recurrence after transplantation.…”