What are the causes of elevated bilirubin and liver transaminases (alanine transaminase (ALT) and aspartate transaminase (AST))?

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From the Guidelines

Elevated bilirubin and liver transaminases indicate liver dysfunction that requires prompt medical evaluation, and patients should seek immediate medical attention for proper diagnosis and management. The most recent and highest quality study, 1, published in 2023, provides guidelines for evaluating patients with abnormal liver function tests. According to this study, hepatocellular predominant abnormal liver function tests are reflected as an increase in aminotransferases, ALT, and AST.

Initial Evaluation

The initial evaluation should include:

  • Complete liver function tests, including ALT, AST, alkaline phosphatase, and bilirubin
  • Hepatitis serologies, such as HAV-IgM, HBsAg, and Hepatitis B core antibody-IgM fraction (HBcIgM), HCV antibody
  • Autoimmune markers, such as ANA/ASMA/ANCA
  • Imaging studies, such as ultrasound or CT scan

Management

Initial management includes discontinuing potential hepatotoxic medications and alcohol consumption. Treatment depends on the underlying cause:

  • Antiviral medications for viral hepatitis
  • Corticosteroids for autoimmune hepatitis
  • Endoscopic procedures for biliary obstruction Supportive care includes adequate hydration, nutritional support, and monitoring for complications like coagulopathy or encephalopathy.

Prognosis and Follow-up

The prognosis varies based on the cause and extent of liver damage, with some conditions being reversible with appropriate treatment while others may progress to chronic liver disease. Regular follow-up with a hepatologist is essential to monitor liver function and adjust treatment as needed, as recommended by 1 and 1.

Key Considerations

  • Liver biopsy may be considered in patients with chronic HCV viremia and either normal or abnormal serum ALT levels, as suggested by 1.
  • For isolated elevation of transaminases, consider checking CK for other etiologies, as recommended by 1.
  • If suspicion for primary autoimmune hepatitis is high, can consider ANA/ASMA/ANCA, as suggested by 1.

From the FDA Drug Label

Free and total serum copper, SGOT and serum bilirubin all showed mean increases over baseline in the untreated group which were significantly larger than with the patients treated with trientine hydrochloride

  • Elevated bilirubin and liver transaminases are affected by the treatment with trientine hydrochloride.
  • The treatment with trientine hydrochloride shows a more favorable outcome in terms of liver function tests, including bilirubin and SGOT, compared to the untreated group.
  • The use of trientine hydrochloride may help to stabilize or improve liver function in patients with Wilson's disease, as evidenced by the changes in serum bilirubin and liver transaminases 2.

From the Research

Elevated Bilirubin and Liver Transaminases

Elevated bilirubin and liver transaminases can be indicative of significant underlying liver disease. The evaluation of these conditions relies on a comprehensive medical history, review of systems, and physical examination.

  • Initial laboratory evaluation should include:
    • Fractionated bilirubin to determine whether the hyperbilirubinemia is conjugated or unconjugated 3, 4
    • Complete blood count
    • Alanine transaminase and aspartate transaminase levels
    • Alkaline phosphatase and gamma-glutamyltransferase levels
    • Prothrombin time and/or international normalized ratio
    • Albumin and protein levels

Causes of Elevated Bilirubin and Liver Transaminases

The causes of elevated bilirubin and liver transaminases can be categorized into:

  • Conjugated hyperbilirubinemia, which occurs in disorders of hepatocellular damage, such as viral and alcoholic hepatitis, and cholestatic disorders, such as choledocholithiasis and neoplastic obstruction of the biliary tree 3
  • Unconjugated hyperbilirubinemia, which occurs with increased bilirubin production caused by red blood cell destruction, such as hemolytic disorders, and disorders of impaired bilirubin conjugation, such as Gilbert syndrome 3
  • Mildly elevated liver transaminase levels, which can be caused by nonalcoholic fatty liver disease, alcoholic liver disease, drug-induced liver injury, hepatitis B and C, and hereditary hemochromatosis 5, 6, 7

Evaluation and Management

The evaluation and management of elevated bilirubin and liver transaminases depend on the underlying cause.

  • Imaging with ultrasonography or computed tomography can help differentiate between extrahepatic obstructive and intrahepatic parenchymal disorders 3, 4
  • A trial of lifestyle modification, such as weight loss and avoidance of hepatotoxic drugs, may be appropriate for patients with mildly elevated transaminase levels 5, 6, 7
  • Referral for further evaluation and possible liver biopsy is recommended if transaminase levels remain elevated for six months or more 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Evaluation of Jaundice in Adults.

American family physician, 2017

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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