Serum Bile Acids as a Prognostic Biomarker in Biliary Atresia Following Kasai Portoenterostomy

Authors

Sanjiv Harpavat
Kieran Hawthorne
Kenneth D R Setchell
Monica Narvaez Rivas
Lisa Henn
Charlotte A Beil
Saul J Karpen
Vicky L Ng
Estella M Alonso
Jorge A Bezerra
Stephen L Guthery
Simon Horslen
Kathy M Loomes
Patrick McKiernan
John C Magee
Robert M Merion
Jean P Molleston
Philip Rosenthal
Richard J Thompson
Kasper S Wang
Ronald J Sokol
Benjamin L Shneider
Childhood Liver Disease Research Network (ChiLDReN)

Publication Date

3-1-2023

Journal

Hepatology

DOI

10.1002/hep.32800

PMID

36131538

PMCID

PMC9936974

PubMedCentral® Posted Date

2-17-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Infant, Humans, Child, Biliary Atresia, Portoenterostomy, Hepatic, Prognosis, Bilirubin, Bile Acids and Salts, Biomarkers, Treatment Outcome, Retrospective Studies

Abstract

BACKGROUND AND AIMS: In biliary atresia, serum bilirubin is commonly used to predict outcomes after Kasai portoenterostomy (KP). Infants with persistently high levels invariably need liver transplant, but those achieving normalized levels have a less certain disease course. We hypothesized that serum bile acid levels could help predict outcomes in the latter group.

APPROACH AND RESULTS: Participants with biliary atresia from the Childhood Liver Disease Research Network were included if they had normalized bilirubin levels 6 months after KP and stored serum samples from the 6-month post-KP clinic visit ( n = 137). Bile acids were measured from the stored serum samples and used to divide participants into ≤40 μmol/L ( n = 43) or >40 μmol/L ( n = 94) groups. At 2 years of age, the ≤40 μmol/L compared with >40 μmol/L group had significantly lower total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, bile acids, and spleen size, as well as significantly higher albumin and platelet counts. Furthermore, during 734 person-years of follow-up, those in the ≤40 μmol/L group were significantly less likely to develop splenomegaly, ascites, gastrointestinal bleeding, or clinically evident portal hypertension. The ≤40 μmol/L group had a 10-year cumulative incidence of liver transplant/death of 8.5% (95% CI: 1.1%-26.1%), compared with 42.9% (95% CI: 28.6%-56.4%) for the >40 μmol/L group ( p = 0.001).

CONCLUSIONS: Serum bile acid levels may be a useful prognostic biomarker for infants achieving normalized bilirubin levels after KP.