It is important to note the difference between “direct” and “conjugated” hyperbilirubinemia Direct bilirubin assays measure conjugated plus some unconjugated and delta bilirubin Direct bilirubin reference intervals will vary across hospitals, due to laboratory specifics including pH, temperature, and reaction time Conjugated bilirubin assays, on the other hand, measure only the mono- and diconjugated forms of bilirubin using direct spectrophotometry Conjugated bilirubin assays have similar reference intervals across laboratories Thus, using the conjugated bilirubin level (if available) is more specific and values are applicable across locations ETIOLOGIES Once an elevated conjugated bilirubin value has been identified, the next step is to consider the causes that explain the finding A systematic approach to making the diagnosis is helpful ( Fig 44.1 ) The key decision point in the emergency department is to identify those patients with evidence of liver failure Any liver failure requires ICU management for stabilization and further evaluation Any neonate with conjugated hyperbilirubinemia, even if not in liver failure, should be admitted for further workup and most importantly to rule out biliary atresia (BA) A stable, older child not in failure can most often be evaluated as an outpatient after consultation with a pediatric gastroenterologist or hepatologist Conceptually, conjugated hyperbilirubinemia occurs for four reasons: elevation from increased bilirubin production, hepatocyte injury, bilirubin transporter defects, or obstruction Increased bilirubin production: When there is bilirubin overproduction, the abundance of unconjugated bilirubin must be converted to conjugated bilirubin in order for it to be excreted As a result, conjugated bilirubin levels can rise In newborns, red blood cell lysis, ABO incompatibility, G6PD, and cephalohematoma can all cause an abundance of unconjugated and subsequently conjugated bilirubin Hepatocyte injury: Hepatocyte injury from any mechanism will cause the breakdown of the liver cell, which results in the release of conjugated bilirubin into the bloodstream This occurs with liver failure, toxic injury, infections, and metabolic disorders Bilirubin transporter defects: Transporter defects can be acquired in the setting of general liver injury and prevent the normal passage of bile (including conjugated bilirubin) out of the liver Transporter defects can also be isolated only to conjugated bilirubin transport, that is, Dubin–Johnson syndrome In these situations, conjugated bilirubin (but not other components of bile such as