A screening algorithm for the efficient exclusion of biliary atresia in infants with cholestatic jaundice

Jancelewicz, Timothy; Barmherzig, Rebecca; Chung, Catherine T.; Ling, Simon C.; Kamath, Binita M.; Ng, Vicky L.; Amaral, João; O’Connor, Constance M.; Fecteau, Annie; Langer, Jacob C.

doi:10.1016/j.jpedsurg.2014.08.014

Cited by 47 publications

(34 citation statements)

References 30 publications

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“…Infants with BA more frequently had acholic stools, had less failure to thrive, and had more pronounced elevation in biochemical markers of bile duct and canalicular injury, although these features were not uniformly discriminative. More recent reports have added radiologic and histologic features to the investigative paradigm [17–19]. Most of these studies have been single or two-center studies and retrospective in nature.…”

Section: Discussionmentioning

confidence: 99%

Initial assessment of the infant with neonatal cholestasis—Is this biliary atresia?

et al. 2017

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IntroductionOptimizing outcome in biliary atresia (BA) requires timely diagnosis. Cholestasis is a presenting feature of BA, as well as other diagnoses (Non-BA). Identification of clinical features of neonatal cholestasis that would expedite decisions to pursue subsequent invasive testing to correctly diagnose or exclude BA would enhance outcomes. The analytical goal was to develop a predictive model for BA using data available at initial presentation.MethodsInfants at presentation with neonatal cholestasis (direct/conjugated bilirubin >2 mg/dl [34.2 μM]) were enrolled prior to surgical exploration in a prospective observational multi-centered study (PROBE–NCT00061828). Clinical features (physical findings, laboratory results, gallbladder sonography) at enrollment were analyzed. Initially, 19 features were selected as candidate predictors. Two approaches were used to build models for diagnosis prediction: a hierarchical classification and regression decision tree (CART) and a logistic regression model using a stepwise selection strategy.ResultsIn PROBE April 2004-February 2014, 401 infants met criteria for BA and 259 for Non-BA. Univariate analysis identified 13 features that were significantly different between BA and Non-BA. Using a CART predictive model of BA versus Non-BA (significant factors: gamma-glutamyl transpeptidase, acholic stools, weight), the receiver operating characteristic area under the curve (ROC AUC) was 0.83. Twelve percent of BA infants were misclassified as Non-BA; 17% of Non-BA infants were misclassified as BA. Stepwise logistic regression identified seven factors in a predictive model (ROC AUC 0.89). Using this model, a predicted probability of >0.8 (n = 357) yielded an 81% true positive rate for BA; <0.2 (n = 120) yielded an 11% false negative rate.ConclusionDespite the relatively good accuracy of our optimized prediction models, the high precision required for differentiating BA from Non-BA was not achieved. Accurate identification of BA in infants with neonatal cholestasis requires further evaluation, and BA should not be excluded based only on presenting clinical features.

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Section: Discussionmentioning

confidence: 99%

Initial assessment of the infant with neonatal cholestasis—Is this biliary atresia?

et al. 2017

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“…However, neonatal jaundice is a common sign for several clinical syndromes. Clinical algorithms have been proposed to differentiate BA from other causes of neonatal cholestasis (7, 11, 12), but they are imprecise and have the potential to delay the diagnosis and treatment (12). …”

Section: Introductionmentioning

confidence: 99%

Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia

et al. 2017

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Biliary atresia is a progressive infantile cholangiopathy of complex pathogenesis. Although early diagnosis and surgery are the best predictors of treatment response, current diagnostic approaches are imprecise and time consuming. We used large-scale, quantitative serum proteomics at the time of diagnosis of biliary atresia and other cholestatic syndromes (serving as disease controls) to identify biomarkers of disease. In a discovery cohort of 70 subjects, the lead biomarker was matrix metalloproteinase-7 (MMP-7), which retained high distinguishing features for biliary atresia in two validation cohorts. Notably, the diagnostic performance reached 95% when MMP-7 was combined with gamma-glutamyltranspeptidase (GGT), a marker of cholestasis. Using human tissue and experimental model of biliary atresia, we found that MMP-7 is primarily expressed by cholangiocytes, is released upon epithelial injury, and promotes the experimental disease phenotype. Thus, we propose that serum MMP-7 (alone or in combination with GGT) is a diagnostic biomarker for biliary atresia and may serve as a therapeutic target.

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“…In summary, none of the aforementioned US signs are sufficiently reliable alone. Therefore, US should not be the sole procedure used on which the differentiation is based (30). A recent study evaluated the competence of high resolution ultrasound (HUS) instead of the conventional one.…”

Section: Neonatal and Infant Chronic Liver Diseasementioning

confidence: 99%

The role of conventional ultrasound in pediatric chronic liver diseases

Kekez¹

2016

Pedaiatr Today

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The aim of this article is to provide an overview of conventional ultrasound in imaging chronic liver diseases in children. The first part describes the normal ultrasound appearance of a child`s liver and the concepts of examination. The further sections present the usual ultrasound findings, the key sonographic points of the most common chronic paediatric liver conditions, and the role of ultrasound in providing diagnostic and prognostic information, detecting complications and supporting reassuring liver biopsy. The limitations of the method are also discussed. Taking all this into account, the interpretation of ultrasound is better in the context of the clinical picture and, in inconclusive cases, followed up with additional imaging and laboratory work up. Conclusion -In conclusion, regardless of the progress made in diagnostic methodology, ultrasound still remains the first, but mostly not the last imaging modality for presumed chronic liver diseases, in daily clinical practice.

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A screening algorithm for the efficient exclusion of biliary atresia in infants with cholestatic jaundice

Cited by 47 publications

References 30 publications

Initial assessment of the infant with neonatal cholestasis—Is this biliary atresia?

Initial assessment of the infant with neonatal cholestasis—Is this biliary atresia?

Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia

The role of conventional ultrasound in pediatric chronic liver diseases

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