What is the cause of new elevated liver enzymes (transaminitis) with aspartate aminotransferase (AST) of 100 and alanine aminotransferase (ALT) of 140?

From the Guidelines

For new transaminitis with AST 100 and ALT 140, the most likely cause is hepatocellular injury, and a comprehensive laboratory workup is recommended to identify the underlying cause, with consideration of non-alcoholic fatty liver disease (NAFLD) as a possible cause, especially if the patient has risk factors such as obesity, diabetes, or dyslipidemia 1. The initial evaluation should include a complete metabolic panel, complete blood count, coagulation studies (PT/INR), and hepatitis serologies (A, B, and C) to rule out other potential causes of liver injury.

• Additional tests should include:
  • Iron studies (ferritin, transferrin saturation) to evaluate for hemochromatosis
  • Ceruloplasmin to evaluate for Wilson disease
  • Alpha-1 antitrypsin levels to evaluate for alpha-1 antitrypsin deficiency
  • Autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody) to evaluate for autoimmune hepatitis
• An abdominal ultrasound should also be performed to evaluate liver structure and rule out other potential causes of liver injury, such as bile duct obstruction or liver masses. Patients should temporarily discontinue potentially hepatotoxic medications and alcohol consumption while the evaluation is ongoing.
• The AST:ALT ratio is generally >2 in alcohol-induced fatty liver disease and <1 in metabolic disease-related fatty liver, which can help guide the diagnosis 1.
• If the patient has risk factors for NAFLD, such as obesity, diabetes, or dyslipidemia, this should be considered as a possible cause, and further evaluation and management should be guided by the most recent clinical guidelines 1. For persistent or worsening transaminitis, referral to a gastroenterologist or hepatologist is appropriate to guide further evaluation and management.
• The mild elevation (less than 5 times upper limit of normal) suggests a chronic process rather than acute severe liver injury, but identifying the specific etiology is crucial for appropriate management and preventing progression to more severe liver disease 1.

From the FDA Drug Label

Patients with mildly elevated liver enzymes (ALT levels at 1 to 2. 5 times the upper limit of normal) at baseline or any time during therapy with ACTOS should be evaluated to determine the cause of the liver enzyme elevation.

The cause of new elevated liver enzymes (transaminitis) with aspartate aminotransferase (AST) of 100 and alanine aminotransferase (ALT) of 140 in a patient taking pioglitazone is unknown and should be evaluated to determine the cause of the liver enzyme elevation 2.

From the Research

Possible Causes of Elevated Liver Enzymes

The causes of elevated liver enzymes, such as aspartate aminotransferase (AST) of 100 and alanine aminotransferase (ALT) of 140, can be varied. Some possible causes include:

• Non-alcoholic fatty liver disease (NAFLD) 3
• Alcohol intake 3, 4
• Hepatitis C virus infection 3
• Viral hepatitis 4
• Genetic liver diseases, such as Wilson's disease or hemochromatosis 4
• Drug-induced liver diseases 4, 5
• Infiltrating liver diseases 4
• Bacterial sepsis 6
• Immune checkpoint inhibitor immunotherapy-related immunotoxicity 5

Diagnostic Approach

A rational approach to the differential diagnosis of elevated liver enzymes is necessary to avoid overdiagnosis while not missing rare causes of liver disease 7. This approach may include:

• Laboratory tests, such as viral serology, autoantibodies, and liver function tests 3
• Imaging studies, such as abdominal ultrasound 3
• Liver biopsy, which may be reserved for patients with atypical treatment response or unclear diagnosis 5

Patterns of Liver Enzyme Elevation

Different patterns of liver enzyme elevation can indicate different underlying causes, such as:

• Predominant increase in transaminase activities, which may indicate hepatocellular integrity disturbance 4
• High serum alkaline phosphatase and γ-glutamyltranspeptidase activities, which may indicate cholestatic liver diseases 4
• Predominant rise in γ-glutamyl transpeptidase, which may be observed in alcoholic or non-alcoholic fatty liver disease and infiltrating liver diseases 4