From the Guidelines
When ALT is higher than AST, the primary focus of further testing should be on evaluating for viral hepatitis, medication-induced liver injury, alcohol-related liver disease, and non-alcoholic fatty liver disease (NAFLD), as indicated by the most recent guidelines 1. The initial step in the diagnostic approach involves understanding the significance of the ALT to AST ratio. Given that ALT elevations are specific for liver injury due to low concentrations in skeletal muscle and kidney, an ALT level higher than AST suggests hepatocellular damage. Key tests to consider in this scenario include:
- Hepatitis serologies (hepatitis A, B, and C) to evaluate for viral hepatitis
- A thorough medication review to identify potential hepatotoxic agents
- Imaging studies such as an ultrasound of the liver to assess for structural abnormalities
- Additional tests like autoimmune markers (ANA, anti-smooth muscle antibody, anti-LKM), iron studies (ferritin, transferrin saturation), and ceruloplasmin levels to rule out Wilson's disease
- Alpha-1 antitrypsin levels for diagnosing alpha-1 antitrypsin deficiency
- A complete metabolic panel, lipid profile, and hemoglobin A1c to assess for metabolic syndrome, commonly associated with NAFLD The pattern of liver enzyme elevation, with ALT being more specific to hepatocellular injury, guides the diagnostic approach, as noted in the recent study 1. If initial testing is inconclusive and liver enzymes remain persistently elevated, a liver biopsy may be necessary for definitive diagnosis, especially when the cause of liver injury remains unclear after initial evaluations.
From the Research
Tests Indicated when Alanine Transaminase (ALT) is Higher than Aspartate Transaminase (AST)
- When ALT is higher than AST, it may indicate acute viral hepatitis 2
- In such cases, the following tests may be indicated:
- Serum lactate dehydrogenase (LD) to differentiate between ischemic hepatitis and viral hepatitis 3
- Autoantibody tests, such as anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (SMA), to rule out autoimmune hepatitis 4, 5, 6
- Viral hepatitis panel to confirm the diagnosis of viral hepatitis 4
- Liver function tests, such as total bilirubin and gamma-globulin, to assess the severity of liver damage 5
- It is essential to calculate the De Ritis ratio (AST/ALT) to provide useful diagnostic and prognostic information 2
- The ALT/LD ratio may also be helpful in differentiating between acute viral hepatitis and other causes of liver injury 3