What is ALT (Alanine Aminotransferase)?
ALT is a liver enzyme that serves as the most specific and important biomarker for detecting hepatocellular injury, with elevations indicating liver cell damage rather than disorders of other organs. 1
Biochemistry and Function
ALT (alanine aminotransferase) is a pyridoxal-dependent enzyme that catalyzes the reversible conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. 2
Two isoforms exist: cytosolic ALT (ALT1) and mitochondrial ALT (ALT2), with ALT1 being the predominant form in liver tissue and primarily responsible for serum ALT activity. 3
ALT1 is highly expressed in liver, skeletal muscle, and kidney, while ALT2 is found predominantly in heart and skeletal muscle but not in liver. 3
Clinical Significance
ALT elevations are highly specific for liver injury because the enzyme is concentrated in hepatocytes with low concentrations in skeletal muscle and kidney, unlike AST which can be elevated from cardiac, skeletal muscle, kidney, brain, and red blood cell disorders. 1
Hepatocellular injury and necrosis from diffuse hepatic infiltration (fat, copper, iron), acute hepatitis, or toxic/ischemic injury causes leakage of ALT from liver cells into serum. 1
ALT is the single most important test for recognition of both acute and chronic hepatic injury. 4
Normal Reference Ranges
Normal ALT levels are 29-33 IU/L (0.48-0.55 µkat/L) in men and 19-25 IU/L (0.32-0.42 µkat/L) in women. 1
More sensitive thresholds have been proposed: ALT >33 U/L in males and >25 U/L in females should be considered elevated, as lower cutoffs may improve early detection of liver disease. 1, 5
Classification of Elevation Severity
ALT elevations are classified as: 1
- Mild: <5 times the upper reference limit
- Moderate: 5-10 times the upper reference limit
- Severe: >10 times the upper reference limit
Common Causes of ALT Elevation
The most common causes of mild ALT increases are: 1
- Nonalcoholic fatty liver disease (NAFLD/MASLD) - prevalence 20-30% in general population, increasing to 70% with obesity and 90% with diabetes
- Alcohol-induced liver disease - typically shows AST:ALT ratio >2
Other causes include: 1
- Acute or chronic viral hepatitis (B and C)
- Drug-induced liver injury
- Autoimmune hepatitis
- Hemochromatosis
- Wilson disease
- Alpha-1-antitrypsin deficiency
Important Clinical Caveats
Patients with NAFLD/MASLD can have normal ALT levels yet still develop significant steatohepatitis, advanced fibrosis, or cirrhosis, so normal ALT does not exclude liver disease. [1, @22@]
ALT levels >300 U/L or >500 IU/L are uncommon in alcoholic hepatitis and should prompt consideration of other etiologies such as acute viral hepatitis, ischemic hepatitis, or acetaminophen toxicity. 1
In isolation, ALT has limited sensitivity and specificity for detecting significant liver disease in asymptomatic populations - only 3.9% of those with abnormal ALT values are diagnosed with significant liver disease within 5 years. 1
ALT should be combined with other diagnostic modalities including imaging, fibrosis assessment tools, and additional liver biochemistry markers to improve diagnostic accuracy. 5