What is the appropriate evaluation and treatment approach for a patient presenting with jaundice, considering potential underlying conditions such as liver disease or bile duct obstruction, and taking into account the patient's age, whether an adult or newborn?

Evaluation and Management of Jaundice

Begin evaluation of jaundice with laboratory testing to differentiate unconjugated from conjugated hyperbilirubinemia, followed immediately by abdominal ultrasound as the first-line imaging study, as this approach allows rapid identification of life-threatening causes including biliary obstruction, sepsis, and malignancy. 1

Initial Laboratory Assessment

Obtain the following tests immediately upon presentation:

• Total and fractionated bilirubin (conjugated vs. unconjugated) to categorize the type of hyperbilirubinemia 1, 2
• Complete blood count to assess for hemolysis 1, 2
• Liver enzymes (AST, ALT) to evaluate hepatocellular injury 1, 2
• Alkaline phosphatase and gamma-glutamyltransferase to identify cholestatic patterns 3, 2
• Albumin, prothrombin time, and INR to assess hepatic synthetic function 4, 2

Laboratory Pattern Interpretation

Alkaline phosphatase elevation suggests cholestatic (post-hepatic) causes such as biliary obstruction, while transaminase elevation suggests hepatocellular (hepatic) causes such as hepatitis or drug-induced liver injury. 3

• Unconjugated hyperbilirubinemia suggests hemolysis, Gilbert syndrome, or hepatocellular dysfunction from hepatitis, sepsis, or drug-induced liver disease 1, 3
• Conjugated hyperbilirubinemia indicates biliary obstruction from stones, malignancy, strictures, or intrahepatic cholestasis 1, 3
• Mixed patterns can occur in severe hepatic disease or sepsis, requiring imaging correlation to differentiate intrahepatic from extrahepatic obstruction 3

Imaging Strategy

Abdominal ultrasound is the mandatory first-line imaging study for all jaundiced patients with conjugated hyperbilirubinemia. 1

Ultrasound Findings Guide Next Steps:

• If biliary dilation is present: Proceed to MRCP or ERCP depending on whether therapeutic intervention is anticipated 1
• If CBD stones are suspected: Sensitivity increases when combining tissue harmonic imaging with elevated bilirubin, patient age, and CBD dilation 1
• If normal CBD caliber: This has high negative predictive value for choledocholithiasis in symptomatic gallstone patients 1
• If multiple small gallstones present: Increased risk for CBD migration requires heightened surveillance 1

Additional imaging with CT with IV contrast or MRCP may be necessary based on ultrasound findings and clinical suspicion for malignancy or complex biliary pathology. 1

Common Etiologies by Geographic Context

In the United States, the four most common causes are:

1. Hepatitis (viral, autoimmune, or drug-induced) 5
2. Alcoholic liver disease 5
3. Common bile duct obstruction (gallstones or tumor) 5
4. Toxic drug reactions or medicinal herbs 5

In U.S. inpatient settings, sepsis is the most common cause (22%), followed by decompensated chronic liver disease (20.5%), alcoholic hepatitis (16%), and gallstone disease (14%). 5

Critical Clinical Pitfalls

Sepsis can cause both hemolysis and hepatic dysfunction, creating mixed unconjugated and conjugated hyperbilirubinemia—laboratory fractionation of bilirubin is essential in these cases. 3

Patients presenting with right upper quadrant pain, fever, and jaundice require urgent evaluation for cholangitis, which demands immediate intervention to prevent mortality. 5

In severe hepatic disease, intrahepatic cholestasis can mimic extrahepatic obstruction on laboratory testing—imaging is mandatory to differentiate these conditions as management differs fundamentally. 3

Special Population: Newborns

For newborns with jaundice on day 2 of life, sepsis must be excluded urgently as it causes both hemolysis and hepatic dysfunction. 6

• Risk factors requiring aggressive monitoring: Gestational age <38 weeks, exclusive breastfeeding with poor intake, and East Asian ethnicity 6
• Jaundice persisting beyond 3 weeks requires measurement of total and direct bilirubin to identify cholestasis 1

When Diagnosis Remains Unclear

If the etiology remains unclear despite laboratory testing and imaging, liver biopsy may be required to establish diagnosis, prognosis, and guide management. 2