Approach to the Patient with Jaundice or Abnormal Liver Tests

Bilirubin metabolism reflects the balance between bilirubin production and clearance. Jaundice is the clinical manifestation of hyperbilirubinemia and the result of bilirubin overproduction, decreased bilirubin clearance, or a combination of both processes. Bilirubin is commonly categorized as either indirect or direct. Indirect hyperbilirubinemia arises from increased bilirubin production from the increased turnover of heme-containing protein or decreased bilirubin conjugation with compounds that aid its clearance. Gilbert syndrome, which is the most frequent disorder of indirect hyperbilirubinemia, is associated with a UDG-glucuronosyltransferases 1A1 gene polymorphism that results in its decreased transcription. Direct or mixed hyperbilirubinemia often reflects disorders of bilirubin clearance at all stages of bilirubin removal, including inherited and acquired disruption of canalicular bile transport, liver diseases that impair organ function, mechanical obstruction of bile flow, or disruption of enterohepatic circulation. The cause of the bilirubin elevation can be deduced by the bilirubin fraction that is elevated, the presence of forms of bilirubin in urine, the clinical history, and other laboratory findings, particularly hepatic enzymes and protein products. Similar to the approach to bilirubin, the evaluation of abnormal liver biochemistries relies on an appreciation of the origin and pattern of the biochemical abnormalities, as well as the clinical context in which they occur. Biochemical abnormalities can be described as hepatocellular, cholestatic (affecting bile flow), or mixed. The diagnosis of the cause of biochemical abnormalities often requires serologic studies, liver imaging, and liver biopsy.