levated aminotransferase levels (above 1000 U/L) can be caused by conditions such as viral hepatitis (types A to E), drug or toxin-induced liver damage, ischemic hepatitis, and, less commonly, autoimmune hepatitis, acute Budd-Chiari syndrome, Wilson’s disease in its acute stage, and bile duct obstruction. The ratio of AST to ALT is particularly useful for diagnosing alcoholic liver disease. When AST levels are below 300 U/L, an AST/ALT ratio greater than 2 indicates alcoholic liver disease, and a ratio exceeding 3 strongly suggests it. This is due to a deficiency of pyridoxal 5′-phosphate in alcoholics, which is more essential for ALT synthesis than for AST. Even when a person with chronic alcoholic liver disease experiences additional liver damage, such as from acetaminophen toxicity, the AST/ALT ratio remains relatively stable despite significant enzyme elevation.
An increased AST/ALT ratio can also be seen in muscle disorders, though levels typically remain below 300 U/L. In rare cases like rhabdomyolysis, values similar to those in acute liver disease may occur. Initially, muscle injury may cause an AST/ALT ratio greater than 3:1, but this shifts toward 1:1 due to AST’s shorter half-life. Chronic muscle diseases usually result in an AST/ALT ratio close to 1:1.
In patients with chronic viral hepatitis or nonalcoholic fatty liver disease (NAFLD- now named MASLD), the AST/ALT ratio is generally below 1. However, as cirrhosis develops, the ratio may rise above 1.
For those with chronic hepatitis C, an AST/ALT ratio greater than 1 is highly specific (94% to 100%) for cirrhosis but has low sensitivity (44% to 75%). The rising ratio is thought to result from reduced blood flow through the liver, limiting the uptake of AST by liver cells.
Most patients with elevated aminotransferase levels are asymptomatic and show mild increases (up to five times the normal level) detected during routine tests. If these levels persist, the first step is to recheck the values. A detailed history is essential, focusing on all medications, including over-the-counter drugs, alternative treatments, and substances of abuse. This can help identify a potential cause, as many substances, including NSAIDs, antibiotics, statins, anti-seizure drugs, and tuberculosis treatments, can raise aminotransferase levels. Often, stopping the medication will normalize enzyme levels. Reintroducing the drug and observing a subsequent rise in enzyme levels can confirm the cause, although this approach is not commonly used. Additionally, muscle diseases should be ruled out by checking serum creatine kinase and aldolase levels.
The rise in ALT and AST as predominant over the rest of the liver test is known as hepatocellular, hepatitic or cytolytic profile as both are the majority of the enzymes in the liver.