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

Abstract

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.

Transient elastography is useful in diagnosing biliary atresia and predicting prognosis after hepatoportoenterostomy

“…Early HPE is associated with an increased probability of a jaundice‐free status 3 months postsurgery, as well as better clinical outcomes, but accurately diagnosing BA in cholestatic infants remains challenging . A recent multicenter study using the classification and regression decision tree (CART) predictive model reported an 81% true‐positive rate and an 11% false‐negative rate for BA . Despite the high accuracy of the optimized prediction models in the CART study, the high precision required for differentiating BA was not achieved .…”

“…A recent multicenter study using the classification and regression decision tree (CART) predictive model reported an 81% true‐positive rate and an 11% false‐negative rate for BA . Despite the high accuracy of the optimized prediction models in the CART study, the high precision required for differentiating BA was not achieved . Liver biopsy may assist in the diagnosis and assessment of LF status in cholestatic infants, but is invasive.…”

“…B). A GGT level >200 IU/L was used as a diagnostic predictor of BA in a recent study . A GGT level >200 IU/L and LSM >7.7 kPa were predictive of BA in univariate logistic regression analyses (OR = 10.21 and 128; P = 0.001 and <0.001, respectively; Table ).…”

“…Early diagnosis and HPE is the gold‐standard treatment and improves the survival of BA patients . Early HPE is associated with an increased probability of a jaundice‐free status 3 months postsurgery, as well as better clinical outcomes, but accurately diagnosing BA in cholestatic infants remains challenging . A recent multicenter study using the classification and regression decision tree (CART) predictive model reported an 81% true‐positive rate and an 11% false‐negative rate for BA .…”

“…Early HPE is associated with a jaundice‐free status 3 months postsurgery, a higher rate of native liver survival, and better clinical outcomes . However, early diagnosis of BA remains challenging in infants with cholestasis . Imaging of the gallbladder and biliary tree under sonographic and magnetic resonance cholangiopancreatography examination are widely used to diagnose BA in cholestatic infants, but the diagnostic accuracy of these tests are unsatisfactory .…”