Serum Markers May Distinguish Biliary Atresia From Other Forms of Neonatal Cholestasis

Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
Journal of pediatric gastroenterology and nutrition (Impact Factor: 2.63). 02/2010; 50(4):411-6. DOI: 10.1097/MPG.0b013e3181cb42ee
Source: PubMed


Biliary atresia (BA) is the most serious liver disease in infants. Diagnosis currently depends on surgical exploration of the biliary tree. Noninvasive tests that distinguish BA from other types of neonatal liver disease are not available.
To identify potential serum biomarkers that classify children with neonatal cholestasis, we performed 2-dimensional difference gel electrophoresis, statistical analysis, and tandem mass spectrometry using serum samples from 19 infants with BA and 19 infants with non-BA neonatal cholestasis.
Eleven potential serum biomarkers were found that could in combination classify children with neonatal cholestasis.
Although no single biomarker or imaging test adequately distinguishes BA from other types of neonatal cholestasis, combinations of biomarkers, imaging tests, and noninvasive clinical criteria should be further explored as potential tests for rapid and accurate diagnosis of BA.

Download full-text


Available from: Robert Heuckeroth, Oct 31, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Protein biomarker discovery from biological fluids, such as serum, has been widely applied to disorders such as cancer and has more recently also been utilized in neuro-psychiatric disorders with relatively clear biological causes, such as Alzheimer's disease and schizophrenia. The application of the associated technologies for the identification of protein biomarker signatures in neurodevelopmental disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder, is comparatively less well established. The aim of this article is to provide an overview of the various protocols available for such analysis, discuss reports in which these techniques have been previously applied in biomarker discovery/validation in neurodevelopmental disorders, and consider the future development of this area of research.
    No preview · Article · Feb 2011 · Expert Review of Proteomics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The persistence of jaundice beyond the first 2 weeks of life require further investigation and this can be determined if the conjugated bilirubin levels are greater than 1.5 mg/dL or greater than 20% of the total bilirubin level. There is a diverse differential diagnosis for the cause of neonatal cholestasis due to hepatobiliary disease including biliary atresia, which eventually leads to liver cirrhosis if uncorrected before 60~80 days of life. Long-established initial studies include abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy, but better diagnostic methods are needed. Promising new options are described including MRCP (magnetic resonance cholangiography), ERCP (endoscopic retrograde cholangiography), and PCC (percutaneous cholecysto-cholangiography). Though no single test can differentiate biliary atresia from other neonatal cholestasis with confidence, a combination of diagnostic methods is usually consistently beneficial. By excluding biliary atresia as early as possible, the risk of unnecessary explolaparotomy with intraoperative cholangiography is decreased. Further evaluation would be required for the diagnosis of neonatal cholestasis after excluding biliary atresia.
    Full-text · Article · Jun 2011
  • [Show abstract] [Hide abstract]
    ABSTRACT: : There is an urgent need to identify noninvasive and convenient biomarkers for early diagnosis of biliary atresia (BA). The aim of the present study was to identify potential protein biomarkers for BA. : Serum samples from 42 infants with BA, 38 infants with non-BA neonatal cholestasis (NC), and 36 healthy controls (HC) were randomly divided into a training set and a test set. Serum proteomic profiles were measured using surface-enhanced desorption/ionization time-of-flight mass spectrometry. Candidate biomarkers were purified using high-performance liquid chromatography, identified using liquid chromatography tandem mass spectrometry, and validated using enzyme-linked immunosorbent assay. : A total of 2 protein peaks (m/z with 8697 and 9098 Da) with differential expression levels were found using surface-enhanced desorption/ionization time-of-flight mass spectrometry. These peaks were then analyzed by a support vector machine to construct a classification model in the training set. The sensitivity and specificity of the model were 94.1% and 91.8%, respectively, in the test set. One candidate biomarker (9098 Da) was identified as Apo C-II, and was found to be downregulated in BA samples compared with HC samples, and upregulated in BA samples compared with NC samples. The other candidate biomarker (8697 Da) was identified as Apo C-III, and was found to be upregulated in BA compared with NC and HC. : Apo C-II and Apo C-III may be potential protein biomarkers of BA and may be useful in distinguishing infants with BA from healthy and NC infants. Further studies with additional populations or using prediagnostic serum are needed to confirm the importance of these findings as diagnostic markers of infants with BA.
    No preview · Article · May 2012 · Journal of pediatric gastroenterology and nutrition
Show more