What is the cause of Transaminitis (Elevated Liver Enzymes)?

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Last updated: February 20, 2025View editorial policy

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From the Guidelines

Transaminitis is most commonly caused by nonalcoholic fatty liver disease (NAFLD) and alcohol-induced liver disease, with the former being the most prevalent liver disease in first-world countries, affecting 20-30% of the general population 1. To address transaminitis, it is essential to identify and treat the underlying cause. The following steps can be taken:

  • Identify and treat the underlying cause, which may include viral hepatitis, alcohol use, medications, or other liver conditions.
  • Stop or modify any hepatotoxic medications or substances.
  • Recommend lifestyle changes:
    • Avoid alcohol consumption
    • Maintain a healthy diet low in saturated fats and high in fruits and vegetables
    • Exercise regularly to reduce fatty liver disease risk
  • Monitor liver enzymes with regular blood tests (every 2-4 weeks initially, then less frequently as levels improve).
  • Consider liver-protective supplements under medical supervision:
    • Milk thistle: 150 mg, three times daily
    • N-acetylcysteine (NAC): 600-1200 mg daily
  • Treat specific conditions if identified:
    • For viral hepatitis: Antiviral medications as prescribed
    • For autoimmune hepatitis: Immunosuppressants like prednisone or azathioprine
  • In severe cases or persistent elevation, refer to a hepatologist for further evaluation and management. It is crucial to note that transaminases are released when liver cells are damaged, so elevated levels indicate ongoing liver injury. Addressing the root cause and supporting liver health can help normalize these enzyme levels and prevent further damage. Regular monitoring is essential to assess improvement and adjust treatment as needed 1. Key points to consider when evaluating transaminitis include:
  • The severity of abnormal aminotransferase can be classified as mild, moderate, or severe, with moderate and severe being discussed collectively due to significant clinical overlap 1.
  • Pathologically increased levels of ALP may occur in cholestatic liver disease, which can show elevated ALP with or without elevated bilirubin 1.
  • The AST:ALT ratio is generally >2 in alcohol-induced fatty liver disease and <1 in metabolic disease-related fatty liver 1.

From the FDA Drug Label

Hepatotoxicity manifest by elevation of serum alkaline phosphatase, bilirubin, and/ or serum transaminases is known to occur following azathioprine use, primarily in allograft recipients. The cause of Transaminitis (Elevated Liver Enzymes) is azathioprine use, which can lead to hepatotoxicity.

  • Key factors that contribute to this risk include:
    • Genetic polymorphisms that affect the activity of enzymes such as TPMT and NUDT15, which are involved in the metabolism of azathioprine 2
    • Dose and duration of therapy, with higher doses and longer treatment durations increasing the risk of hepatotoxicity 2
  • Monitoring of liver function tests, including serum transaminases, alkaline phosphatase, and bilirubin, is recommended to detect hepatotoxicity early 2

From the Research

Causes of Transaminitis (Elevated Liver Enzymes)

  • Hepatocellular damage, as indicated by elevated serum levels of transaminases (AST and ALT) 3
  • Extrahepatic origin, such as muscle damage, which can cause ALT elevations 3
  • Alcoholic liver disease, which can be identified by a higher ratio of AST/ALT and mitochondrial isoenzyme of AST 3
  • Viral hepatitis, including hepatitis A, B, C, and E 4, 5
  • Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatosis 4, 3
  • Autoimmune hepatitis, hemochromatosis, Wilson's disease, and alpha-1 antitrypsin deficiency 5
  • Drug-induced liver injury (DILI), which can be caused by potentially hepatotoxic medications, including nonsteroidal anti-inflammatory drugs and certain herbal remedies 6, 4, 3
  • Cholestasis, which can cause elevated serum activities of alkaline phosphatase (AP) and gamma-glutamyl transferase (G-GT) 3

Specific Causes and Associations

  • Pulmonary tuberculosis can cause elevated transaminases without pre-existing liver disease 7
  • Marked increase of gamma-glutamyltransferase (GGT) can be an indicator of DILI, even if conventional diagnostic criteria are not met 6
  • Hepatitis C virus infection is a common cause of chronic liver disease and can be synergistic with alcohol in hastening the development of cirrhosis 4

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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