What are the causes of hyperbilirubinemia (elevated bilirubin levels)?

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From the Guidelines

Hyperbilirubinemia should be promptly evaluated and treated based on the underlying cause, severity, and patient age to prevent complications such as kernicterus in newborns or liver dysfunction in adults. The condition occurs when the liver cannot adequately process bilirubin, a yellow pigment produced during the breakdown of red blood cells, leading to elevated levels of bilirubin in the blood and causing yellowing of the skin and eyes (jaundice) 1.

Causes and Evaluation

The causes of hyperbilirubinemia can be categorized into unconjugated (nonobstructive) hyperbilirubinemia, such as hepatitis, sepsis, or drug-induced liver disease, and conjugated (obstructive) hyperbilirubinemia, such as common bile duct obstruction by stones or tumors 1. A detailed history, targeted physical examination, and pertinent laboratory studies, including hepatic profile and complete blood count, are essential for differentiating between the various potential etiologies of jaundice 1.

Treatment

Treatment depends on the cause, severity, and patient age. For newborns with physiologic jaundice, phototherapy is the primary treatment, using special blue lights that help break down bilirubin so it can be excreted 1. In severe cases, exchange transfusion may be necessary. For adults, treatment targets the underlying cause, such as addressing liver disease, treating infections, or discontinuing medications that may be causing the condition. Hydration is important in all cases to help flush bilirubin from the system. In hemolytic conditions causing increased red blood cell breakdown, medications to suppress the immune response may be needed.

Monitoring and Complications

Laboratory monitoring of bilirubin levels guides treatment decisions, with normal total bilirubin levels being less than 1.2 mg/dL. Hyperbilirubinemia requires prompt attention as very high levels can lead to kernicterus in newborns, causing permanent neurological damage, or indicate serious liver dysfunction in adults. It is also important to look for G6PD deficiency in infants with significant hyperbilirubinemia, as some may develop a sudden increase in total serum bilirubin (TSB) levels 1.

Risk Assessment

Risk assessment is crucial in managing hyperbilirubinemia, particularly in newborns. The risk zone can be predicted based on TSB levels before discharge, with higher levels indicating a higher risk of subsequent hyperbilirubinemia 1. Intervention is recommended at lower TSB levels at younger ages to prevent additional increases in the TSB level and potential complications.

From the Research

Definition and Prevalence of Hyperbilirubinemia

  • Hyperbilirubinemia is a condition characterized by elevated total serum bilirubin (TSB) levels, commonly affecting neonates 2.
  • It is estimated that about two thirds of newborns will appear clinically jaundiced during their first weeks of life 3.
  • Hyperbilirubinemia is the most common condition requiring evaluation and treatment in newborns, occurring in 60% of normal newborns and nearly all preterm infants 4.

Clinical Manifestation and Diagnosis

  • The clinical manifestation of hyperbilirubinemia is jaundice, which occurs when serum bilirubin levels exceed 3 mg/dL 5.
  • A comprehensive medical history, review of systems, and physical examination are essential for differentiating potential causes of hyperbilirubinemia 5.
  • Initial laboratory evaluation should include assays for bilirubin (total and fractionated), a complete blood cell count, and liver function tests 5.

Treatment and Management

  • Treatment guidelines for hyperbilirubinemia lack practical recommendations surrounding subthreshold phototherapy, treatment termination, and rebound hyperbilirubinemia investigations 2.
  • Phototherapy is a common treatment for hyperbilirubinemia, and treatment practices such as when to terminate treatment in relation to threshold values, and timing of rebound hyperbilirubinemia investigations, are largely inconsistent amongst clinicians 2.
  • Recommendations are provided for risk stratification and determining the need for phototherapy or exchange transfusion, using nomograms to plot total serum bilirubin levels and taking into consideration hyperbilirubinemia and neurotoxicity risk factors 6.

Complications and Risks

  • Unrecognized or untreated pathologic unconjugated hyperbilirubinemia can lead to the development of acute bilirubin encephalopathy and, ultimately, kernicterus 6.
  • Rebound hyperbilirubinemia is a common complication of hyperbilirubinemia, requiring re-initiation of treatment, and occurs in up to 10% of neonates 2.
  • Hyperbilirubinemia can indicate serious underlying disease of the liver or biliary tract, and a comprehensive evaluation is essential to determine the underlying cause 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hyperbilirubinemia.

Critical care nursing clinics of North America, 2009

Research

Evaluation of Jaundice in Adults.

American family physician, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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