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

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Last updated: May 23, 2025View editorial policy

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From the Guidelines

Elevated bilirubin levels can indicate several diseases, with the most common being liver disorders such as hepatitis, cirrhosis, and Gilbert's syndrome, and the management of these conditions should prioritize reducing morbidity, mortality, and improving quality of life. Bilirubin is a yellowish pigment produced when old red blood cells break down, and it's normally processed by the liver before being excreted. When bilirubin levels rise above normal (typically >1.2 mg/dL for adults), it can cause jaundice, characterized by yellowing of the skin and eyes.

Causes of Elevated Bilirubin

The causes of elevated bilirubin can be categorized into unconjugated and conjugated hyperbilirubinemia. Unconjugated hyperbilirubinemia is usually due to haemolysis or impaired conjugation, whereas conjugated hyperbilirubinemia is typically due to parenchymal liver disease or obstruction of the biliary system 1. The most common cause of an isolated elevated bilirubin concentration is Gilbert’s syndrome, which is an inherited disorder of metabolism and leads to impaired conjugation via reduced activity of the enzyme glucuronyltransferase 1.

Diagnosis and Management

Diagnosis of the underlying cause of elevated bilirubin is crucial, and it typically involves a combination of laboratory tests, including liver function tests, complete blood count, and imaging studies such as ultrasound or CT scan 1. Management of elevated bilirubin depends on the underlying cause, and it may involve supportive care, medication, or surgery. For example, patients with viral hepatitis may require supportive care with rest, hydration, and avoiding alcohol, while those with Gilbert's syndrome may not require any treatment 1.

Prioritizing Morbidity, Mortality, and Quality of Life

In managing elevated bilirubin, it is essential to prioritize reducing morbidity, mortality, and improving quality of life. This may involve early recognition and treatment of underlying liver disease, prevention of complications, and management of symptoms such as jaundice and pruritus. The most recent and highest quality study recommends a comprehensive approach to managing elevated bilirubin, including laboratory tests, imaging studies, and treatment of underlying causes 1.

Key Considerations

Some key considerations in managing elevated bilirubin include:

  • Early recognition and treatment of underlying liver disease
  • Prevention of complications such as liver failure and hepatocellular carcinoma
  • Management of symptoms such as jaundice and pruritus
  • Use of laboratory tests and imaging studies to diagnose and monitor underlying causes
  • Individualized treatment plans based on the underlying cause and severity of disease.

From the Research

Elevated Bilirubin Disease

Elevated bilirubin disease, also known as hyperbilirubinemia, is a condition characterized by high levels of bilirubin in the blood. This can be caused by various factors, including liver disease, biliary tract disease, and hemolysis.

Causes of Elevated Bilirubin

  • Liver disease, such as alcoholic liver disease, hepatitis, and cirrhosis 2, 3
  • Biliary tract disease, such as choledocholithiasis, biliary strictures, and neoplastic obstruction of the biliary tree 2, 3
  • Hemolysis, such as autoimmune hemolytic anemia 4, 5
  • Disorders of impaired bilirubin conjugation, such as Gilbert syndrome 3

Diagnosis and Evaluation

The diagnosis and evaluation of elevated bilirubin disease involve a comprehensive medical history, review of systems, and physical examination 2, 6, 3. Initial laboratory evaluation should include:

  • Fractionated bilirubin
  • Complete blood count
  • Alanine transaminase
  • Aspartate transaminase
  • Alkaline phosphatase
  • Gamma-glutamyltransferase
  • Prothrombin time and/or international normalized ratio
  • Albumin
  • Protein Imaging studies, such as ultrasonography or computed tomography, may also be necessary to differentiate between extrahepatic obstructive and intrahepatic parenchymal disorders 2, 3.

Treatment and Outcome

Treatment of elevated bilirubin disease depends on the underlying cause. Immunosuppressive therapy may be effective in cases of autoimmune hemolytic anemia and giant cell hepatitis 4, 5. Liver transplantation may be necessary in severe cases of liver disease 5. The outcome of elevated bilirubin disease varies depending on the underlying cause and the effectiveness of treatment. In some cases, complete remission or cure may be possible, while in others, the disease may be chronic or fatal 4, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Evaluation of Jaundice in Adults.

American family physician, 2025

Research

Evaluation of Jaundice in Adults.

American family physician, 2017

Research

Diagnosis and evaluation of hyperbilirubinemia.

Current opinion in gastroenterology, 2017

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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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