What is the significance of elevated Alanine Transaminase (ALT) with normal Aspartate Transaminase (AST) levels?

From the Guidelines

Elevated ALT without elevated AST typically indicates liver injury, most commonly due to non-alcoholic fatty liver disease (NAFLD), and management should focus on addressing the underlying cause. According to the American College of Radiology's 2023 guidelines on abnormal liver function tests 1, ALT elevations are specific for liver injury due to low concentrations in skeletal muscle and kidney. 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.

Some key points to consider in the management of elevated ALT without elevated AST include:

• Common causes: obesity, diabetes, metabolic syndrome, certain medications (like statins, NSAIDs, antibiotics), viral hepatitis (especially early stages), and autoimmune hepatitis
• Management: lifestyle modifications for NAFLD (weight loss of 7-10%, Mediterranean diet, regular exercise), medication review to identify potential hepatotoxic drugs, and screening for viral hepatitis and autoimmune conditions
• If ALT is mildly elevated (less than 2-3 times normal), watchful waiting with repeat testing in 3-6 months may be appropriate
• For persistent or significantly elevated ALT levels, further evaluation with ultrasound, additional blood tests, or referral to a hepatologist is recommended, as stated in the 2023 guidelines 1

It's essential to note that the isolated ALT elevation reflects its greater specificity for liver injury compared to AST, which is also found in heart and muscle tissue, making ALT a more reliable indicator of liver-specific damage, as highlighted in the study 1.

From the Research

Elevated ALT but not AST

• Elevated ALT levels can be an indicator of liver damage, as ALT is a more specific marker for liver damage compared to AST 2.
• The presence of an elevated ALT has been associated with increased liver-related mortality 3.
• A true healthy normal ALT level ranges from 29 to 33 IU/l for males, 19 to 25 IU/l for females, and levels above this should be assessed 3.
• The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 3.
• Non-hepatic causes of raised ALT include polymyositis, acute muscle injury, acute myocardial infarction, and hypothyroidism 4.
• Vitamin E has shown beneficial effects on oxidative stress, which plays a major role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), and may slightly reduce serum ALT levels 5.
• The combination of ursodeoxycholic acid (UDCA) and vitamin E is a therapeutic option for nonalcoholic steatohepatitis (NASH) and has been shown to improve liver function tests in long-term 6.

Possible Causes

• Nonalcoholic fatty liver disease (NAFLD) 3, 5
• Nonalcoholic steatohepatitis (NASH) 5, 6
• Viral hepatitis A, B, and C 3
• Alcoholic liver disease 3, 4
• Hereditary hemochromatosis 3
• Autoimmune hepatitis 3
• Wilson's disease 3
• Alpha-1 antitrypsin deficiency 3
• Polymyositis 4
• Acute muscle injury 4
• Acute myocardial infarction 4
• Hypothyroidism 4

Next Steps

• Obtain a complete history regarding the risk factors for viral hepatitis, substance abuse, and request investigations accordingly 4.
• Testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 3.
• Consider referral to a hepatologist for further management 4.