Serum Bile Acid Levels in Children With Nonalcoholic Fatty Liver Disease.
OBJECTIVE
Because the prevalence of obesity in children is increasing, the frequency of pediatric nonalcoholic fatty liver disease (NAFLD) is growing. A reliable noninvasive biomarker for monitoring progression of liver fibrosis would be useful. In cirrhotic persons serum bile acid (BA) levels are significantly elevated. We hypothesized that BA levels and composition in pediatric NAFLD vary depending on the stage of fibrosis.


METHODS
Children with NAFLD were compared with controls and classified by stages of fibrosis (NAFLD-F0, n = 27; NAFLD-F≥1, n = 65) based on liver-biopsy findings. Fasted metabolic and cholestasis status was assessed by several blood tests. BA profiles were measured by tandem mass spectrometry and compared with healthy controls (n = 105).


RESULTS
Compared with controls, all of the NAFLD patients were overweight and showed significantly elevated glucose, insulin, aspartate transaminase, and alanine transaminase levels. Total serum BAs were lower in nonfibrotic NAFLD children than in a control cohort (1.73 vs 3.6 μmol/L) because low glycine-conjugated BA levels were incompletely compensated by increases in taurine-conjugated or unconjugated BA. In patients with fibrotic NAFLD, BA levels were lower than in controls (2.45 vs 3.6 μmol/L) but higher than in nonfibrotic patients (2.45 vs 1.73 μmol/L), and the BA pattern resembled that of healthy controls. Fibroblast growth factor 19 levels were significantly lower in both NAFLD groups than in controls (P ≤ 0.001) and were positively correlated with ursodeoxycholic acid levels.


CONCLUSIONS
Our data indicate that serum BA levels decrease in early NAFLD and increase during progression to fibrosis. Given that BA levels are increased in cirrhotic adults, we postulate a continuous rise as NAFLD advances. BA may have a value as a noninvasive biomarker in pediatric NAFLD progression.
*Department of Pediatrics and Adolescent Medicine †Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria ‡Liver Research Unit §Hepato-Metabolic Disease Unit ||Pathology Department, Bambino Gesù Children's Hospital-Instituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy ¶Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Jörg
J
Jahnel
Evelyn
E
Zöhrer
Anna
A
Alisi
Federica
F
Ferrari
Sara
S
Ceccarelli
Rita
R
De Vito
Hubert
H
Scharnagl
Tatjana
T
Stojakovic
Günter
G
Fauler
Michael
M
Trauner
Valerio
V
Nobili
D000293:Adolescent; D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000097:blood* / Q000209:etiology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000150:complications; D055815:Young Adult
D001647:Bile Acids and Salts