Nyholm, Iiris;
Hukkinen, Maria;
Pihlajoki, Marjut;
Davidson, Joseph R;
Tyraskis, Athanasios;
Lohi, Jouko;
Heikkilä, Päivi;
... Pakarinen, Mikko P; + view all
(2023)
Serum FGF19 predicts outcomes of Kasai portoenterostomy in biliary atresia.
Hepatology
10.1097/HEP.0000000000000048.
(In press).
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Serum FGF19 predicts outcomes of Kasai portoenterostomy in biliary atresia |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1097/HEP.0000000000000048 |
| Publisher version: | http://dx.doi.org/10.1097/HEP.0000000000000048 |
| Language: | English |
| Additional information: | This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of American Association for the Study of Liver Diseases. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10164103 |
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