Serum FGF19 predicts outcomes of Kasai portoenterostomy in biliary atresia.
Iiris Nyholm, Maria Hukkinen, Marjut Pihlajoki, Joseph R Davidson, Athanasios Tyraskis, Jouko Lohi, Päivi Heikkilä, Satu Hänninen, Noora Andersson, Katja Eloranta, Olli Carpén, Markku Heikinheimo, Mark Davenport, Mikko P Pakarinen
Author Information
Iiris Nyholm: Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. ORCID
Maria Hukkinen: Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. ORCID
Marjut Pihlajoki: Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. ORCID
Joseph R Davidson: Department of Pediatric Surgery, GOS-UCL Institute of Child Health, London, UK. ORCID
Athanasios Tyraskis: Department of Pediatric Surgery, King's College Hospital, London, UK.
Jouko Lohi: Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Päivi Heikkilä: Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Satu Hänninen: Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. ORCID
Noora Andersson: Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Katja Eloranta: Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. ORCID
Olli Carpén: Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. ORCID
Markku Heikinheimo: Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. ORCID
Mark Davenport: Department of Pediatric Surgery, King's College Hospital, London, UK. ORCID
Mikko P Pakarinen: Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. ORCID
BACKGROUND AND AIMS: Outcomes after Kasai portoenterostomy (KPE) for biliary atresia remain highly variable for unclear reasons. As reliable early biomarkers predicting KPE outcomes are lacking, we studied the prognostic value of FGF19. APPROACH AND RESULTS: Serum and liver specimens, obtained from biliary atresia patients (N=87) at KPE or age-matched cholestatic controls (N=26) were included. Serum concentration of FGF19 and bile acids, liver mRNA expression of FGF19 , and key regulators of bile acid synthesis were related to KPE outcomes and liver histopathology. Immunohistochemistry and in situ hybridization were used for the localization of liver FGF19 expression. Serum levels (223 vs. 61 pg/mL, p <0.001) and liver mRNA expression of FGF19 were significantly increased in biliary atresia. Patients with unsuccessful KPE (419 vs. 145 pg/mL, p =0.047), and those subsequently underwent liver transplantation (410 vs. 99 pg/mL, p =0.007) had significantly increased serum, but not liver, FGF19, which localized mainly in hepatocytes. In Cox hazard modeling serum FGF19 <109 pg/mL predicted native liver survival (HR: 4.31, p <0.001) also among patients operated <60 days of age (HR: 8.77, p =0.004) or after successful KPE (HR: 6.76, p =0.01). Serum FGF19 correlated positively with increased serum primary bile acids ( R =0.41, p =0.004) and ductular reaction ( R =0.39, p =0.004). CONCLUSIONS: Increased serum FGF19 at KPE predicted inferior long-term native liver survival in biliary atresia and was associated with unsuccessful KPE, elevated serum primary bile acids, and ductular reaction.
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