Why is AST/ALT 2:1 in Alcoholic Hepatitis?

Patients with alcoholic hepatitis almost always have liver markers levels less than 500 IU/L and often have a ratio AST/ALT of 2:1. Elevated gamma-glutamyl transferase supports the diagnosis.

THEORY:
1. ALT= Liver cytoplasmic enzyme (specific for liver cell necrosis). AST= mitochondrial enzyme

• Ethanol (Alcohol) damages the mitochondrial membrane, which is critical to dealing with reactive oxygen species (ROS). Excess ethanol may overwhelm the mitochondria with oxidative stress leading to cellular damage/death. This in term causes increased leakage of mitochondria AST (mAST) into the bloodstream.

2. Decreased ALT activity most likely due to B6 depletion in the livers of alcoholics

REFERENCES

1. Botros M, Sikaris KA. The De Ritis Ratio: The Test of Time. The Clinical Biochemist Reviews. 2013;34(3):117-130.
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3. Ishii H, Okuno F, Shigeta Y, Tsuchiya M. Enhanced serum glutamic oxaloacetic transaminase activity of mitochondrial origin in chronic alcoholics. Curr Alcohol. 1979; 5():101-8.
4.  Serum gamma-glutamyl transpeptidase and chronic alcoholism. Influence of alcohol ingestion and liver disease. Dig Dis Sci 30 (3): 211–4. Mar 1985. doi:10.1007/bf01347885. PMID 2857631.