title: MicroRNAs in the bile of patients with biliary strictures after liver transplantation.
abstract: Biliary complications after liver transplantation remain a major cause of morbidity and reduced graft survival. Ischemic-type biliary lesions (ITBLs) are common and difficult to treat. The pathophysiology of ITBLs remains unclear, and diagnostic markers are still missing. The analysis of microRNA (miRNA) profiles is an evolving field in hepatology. Our aim was to identify specific miRNA patterns in the bile of patients with ITBLs after liver transplantation. Liver transplant patients with biliary complications were included in a cross-sectional study. Patients with ITBLs (n = 37), anastomotic strictures (ASs; n = 39), and bile duct stones (BDSs; n = 12) were compared. Patients with ITBLs were categorized by disease severity. The miRNA concentrations in bile were determined with global miRNA profiling and subsequent miRNA-specific polymerase chain reaction-mediated validation. The concentrations of microRNA 517a (miR-517a), miR-892a, and miR-106a* in bile were increased for patients with ITBLs versus patients with ASs or BDSs (P < 0.05). Categorization by ITBL severity showed higher median concentrations in patients with intrahepatic and extrahepatic strictures (P > 0.05). miR-210, miR-337-5p, miR-577, and miR-329 displayed no statistical differences. In conclusion, miR-517a, miR-892a, and miR-106a* are increased in the bile fluid of patients with ITBLs versus patients with ASs or BDSs. An analysis of miRNA profiles may be useful in the diagnosis and management of patients with ITBLs. Future studies are needed to prove the potential prognostic value of these miRNAs.
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center-Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Tim O
authors.initials: TO
authors.lastname: Lankisch
authors.forename: Torsten
authors.initials: T
authors.lastname: Voigtländer
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Angelika
authors.initials: A
authors.lastname: Holzmann
authors.forename: Seema
authors.initials: S
authors.lastname: Dangwal
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
mesh_terms: D000328:Adult; D000368:Aged; D001646:Bile / Q000737:chemistry*; D002779:Cholestasis / Q000175:diagnosis / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012720:Severity of Illness Index; D015854:Up-Regulation
chemical_list: D005819:Genetic Markers; C542541:MIRN106 microRNA, human; C546349:MIRN517 microRNA, human; C574666:MIRN892 microRNA, human; D035683:MicroRNAs