What are the causes of jaundice in adults and newborns?

Causes of Jaundice in Adults and Newborns

Adults

Jaundice in adults results from four primary mechanisms: bilirubin overproduction, impaired bilirubin conjugation, biliary obstruction, and hepatic inflammation, with the most common causes in the United States being hepatitis, alcoholic liver disease, common bile duct obstruction (by gallstone or tumor), and drug/herbal toxicity. 1

Pathophysiologic Classification

Jaundice is best categorized by laboratory findings into unconjugated (nonobstructive) versus conjugated (obstructive) hyperbilirubinemia, which guides both diagnosis and management 1:

Unconjugated Hyperbilirubinemia Causes:

• Hemolytic disorders causing increased red blood cell destruction and bilirubin overproduction 2
• Gilbert syndrome (accounts for 5.6% of cases) and other inherited bilirubin metabolism defects 1
• Crigler-Najjar syndrome and disorders of impaired bilirubin conjugation 3
• Hematoma resorption 4

Conjugated Hyperbilirubinemia Causes:

Hepatocellular disorders:

• Sepsis (22% of new-onset jaundice cases in U.S. studies, most common single etiology) 1, 3
• Decompensation of pre-existing chronic liver disease (20.5% of cases) 1
• Alcoholic hepatitis (16% of cases) 1
• Viral hepatitis (hepatitis A, B, C) 2
• Drug-induced liver injury and toxic reactions to medications or herbal supplements 1
• Autoimmune hepatitis 1

Biliary obstruction (cholestatic):

• Choledocholithiasis (gallstone disease accounts for 14% of cases) 1, 3
• Malignancy (6.2% in U.S. studies, but most common cause of severe jaundice in European populations) 1, 3
• Cholangitis 1
• Pancreatitis 1

Geographic and Demographic Variations

The dominant etiology varies significantly by geography, hospital type (tertiary referral versus community), and demographics 1:

• U.S. data: Sepsis most common (22%), followed by chronic liver disease decompensation (20.5%) 1
• European data: Malignancy most common cause of severe jaundice 1
• Vietnam data: Cirrhosis most common overall 1

Special Populations

In patients with pre-existing chronic liver disease, specific precipitants include 3:

• Coombs-negative hemolytic anemia (occurs in 10-25% of CLD patients with jaundice) 3
• Copper release from dying hepatocytes aggravating hemolysis, particularly in Wilson's disease 3
• Acute kidney injury compounding jaundice risk in severe alcoholic hepatitis 3

Risk Factors

Key modifiable and non-modifiable risk factors include 3:

• Heavy alcohol consumption (>50 g/day for minimum 6 months) 3
• Female gender (independent risk factor for alcoholic hepatitis) 3
• Elevated BMI (risk factor for both alcoholic and nonalcoholic steatohepatitis) 3
• Genetic polymorphisms (G allele of PNPLA3 increases alcoholic hepatitis susceptibility) 3
• Malnutrition (common in alcoholic hepatitis, impairs recovery) 3

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Newborns

Neonatal jaundice is caused primarily by increased bilirubin production from red blood cell breakdown combined with immature hepatic conjugation capacity, with most term infants experiencing benign "physiological" jaundice. 5

Unconjugated Hyperbilirubinemia (Most Common):

• Physiological jaundice (most common in healthy term infants, caused by immature liver conjugation) 5
• Hemolytic disease (ABO/Rh incompatibility, G6PD deficiency, hereditary spherocytosis) 5
• Breastfeeding jaundice (inadequate intake in first week) 5
• Breast milk jaundice (substances in breast milk inhibiting conjugation, appears after first week) 5
• Crigler-Najjar syndrome and Gilbert syndrome 5

Conjugated Hyperbilirubinemia (Pathologic):

• Biliary atresia (critical diagnosis requiring urgent surgical intervention) 5
• Neonatal hepatitis 5
• Prolonged parenteral nutrition in preterm infants (generally improves with enteral feeding) 5
• Metabolic disorders (galactosemia, tyrosinemia) 5
• Sepsis 5

Critical Distinction

Any infant with persistently elevated bilirubin must have conjugated bilirubin measured to exclude biliary atresia, as this requires urgent surgical intervention to prevent irreversible liver damage 5. Very high levels of unconjugated bilirubin are neurotoxic and can cause kernicterus, requiring urgent phototherapy or exchange transfusion 5.