Godbole, N;
Nyholm, I;
Hukkinen, M;
Davidson, JR;
Tyraskis, A;
Lohi, J;
Heikkilä, P;
... Pakarinen, MP; + view all
(2022)
Liver secretin receptor predicts portoenterostomy outcomes and liver injury in biliary atresia.
Scientific Reports
, 12
(1)
, Article 7233. 10.1038/s41598-022-11140-9.
(In press).
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Abstract
Biliary atresia (BA) is a chronic neonatal cholangiopathy characterized by fibroinflammatory bile duct damage. Reliable biomarkers for predicting native liver survival (NLS) following portoenterostomy (PE) surgery are lacking. Herein we explore the utility of 22 preidentified profibrotic molecules closely connected to ductular reaction (DR) and prevailing after successful PE (SPE), in predicting PE outcomes and liver injury. We used qPCR and immunohistochemistry in a BA cohort including liver samples obtained at PE (n = 53) and during postoperative follow-up after SPE (n = 25). Of the 13 genes over-expressed in relation to cholestatic age-matched controls at PE, only secretin receptor (SCTR) expression predicted cumulative 5-year NLS and clearance of jaundice. Patients in the highest SCTR expression tertile showed 34–55% lower NLS than other groups at 1–5 years after PE (P = 0.006–0.04 for each year). SCTR expression was also significantly lower [42 (24–63) vs 75 (39–107) fold, P = 0.015] among those who normalized their serum bilirubin after PE. Liver SCTR expression localized in cholangiocytes and correlated positively with liver fibrosis, DR, and transcriptional markers of fibrosis (ACTA2) and cholangiocytes (KRT7, KRT19) both at PE and after SPE. SCTR is a promising prognostic marker for PE outcomes and associates with liver injury in BA.
| Type: | Article |
|---|---|
| Title: | Liver secretin receptor predicts portoenterostomy outcomes and liver injury in biliary atresia |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-022-11140-9 |
| Publisher version: | https://doi.org/10.1038/s41598-022-11140-9 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Biliary Atresia, Biomarkers, Humans, Infant, Infant, Newborn, Liver, Portoenterostomy, Hepatic, Receptors, G-Protein-Coupled, Receptors, Gastrointestinal Hormone, Treatment Outcome |
| UCL classification: | UCL 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 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 |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10148847 |
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