When a doctor orders a liver function test, the results often include two specific proteins: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT). These enzymes are typically contained within liver cells, but when the liver is damaged or inflamed, they leak into the bloodstream, where they can be measured. Elevated levels of these transaminases serve as a general indicator of liver cell injury. Calculating the AST/ALT ratio, sometimes called the De Ritis ratio, offers specialized insight beyond the simple elevation of each individual number. This ratio helps medical professionals differentiate between various potential causes of liver injury, providing a more detailed diagnostic picture.
Understanding AST and ALT
Both AST and ALT are transaminase enzymes that play a functional role in amino acid metabolism, facilitating the transfer of an amino group from an amino acid to a ketoacid. Their presence in the blood signals that cellular integrity has been compromised, releasing the enzymes from the cells where they reside.
The location of these two enzymes is the primary reason why their ratio is diagnostically useful. Alanine Aminotransferase (ALT) is highly concentrated within the liver’s primary cells, the hepatocytes, located almost entirely in the cell’s cytoplasm. Because of this concentrated location, a significant rise in ALT is a strong and relatively specific marker for liver injury.
Aspartate Aminotransferase (AST) is also abundant in liver cells, but its distribution is wider across the body and within the cell itself. AST is found in large quantities in other organs, including the heart muscle, skeletal muscle, kidneys, and brain tissue. Furthermore, within the liver cell, AST exists in both a cytoplasmic and a mitochondrial form. This dual location and broader tissue distribution means that elevated AST levels are far less specific to the liver than ALT elevations.
Calculating the AST/ALT Ratio and Normal Values
The AST/ALT ratio is calculated by dividing the measured concentration of Aspartate Aminotransferase by the measured concentration of Alanine Aminotransferase. Since both enzymes are typically reported in the same units, such as units per liter (U/L), the resulting ratio is a unitless number. For example, an AST of 30 U/L and an ALT of 60 U/L yields a ratio of 0.5.
In a healthy individual, the levels of both enzymes are generally low. A normal AST/ALT ratio is usually around 0.8, meaning the ALT level is slightly higher than the AST level. A ratio below 1.0 is the expected finding when both enzymes are within or near the normal range.
The ratio only becomes a significant diagnostic tool when the concentrations of both AST and ALT are elevated above the established upper limits of normal. When levels are within the healthy range, the ratio holds little clinical relevance. Its value lies in helping to pinpoint the specific pattern of liver damage once injury has been confirmed by elevated enzyme levels.
Interpreting a Ratio Below 1.0
A ratio less than 1.0, where the ALT value is higher than the AST value, is a pattern often observed in acute liver injury, especially in its early stages. This situation is referred to as ALT dominance, and it is a common finding in many forms of acute viral hepatitis, such as Hepatitis B or C. The high concentration of ALT in the hepatocyte cytoplasm allows it to leak out rapidly when the cell wall is damaged by a sudden, acute insult.
This ALT-dominant pattern is also characteristic of non-alcoholic fatty liver disease (NAFLD) and its more severe form, non-alcoholic steatohepatitis (NASH). In these conditions, which are linked to the metabolic syndrome, the ratio is typically below 1.0, often falling between 0.5 and 0.8. The inflammation caused by fat accumulation tends to affect the cytoplasmic components of the liver cells more readily, leading to a preferential release of ALT.
Drug-induced liver injury, particularly in its acute presentation, can also cause an ALT-dominant pattern. Since the liver metabolizes medications and toxins, acute damage from these substances often results in the release of cytoplasmic ALT. The presence of a low ratio in the context of elevated transaminases generally points to a process that is either acute or a chronic, non-alcoholic form of liver inflammation.
Interpreting a Ratio Above 1.0
A ratio of 1.0 or greater, where the AST level is equal to or higher than the ALT level, suggests a different kind of injury pattern, often signaling more chronic or severe liver damage. When the ratio is close to 1.0, it is frequently associated with the development of cirrhosis, which is advanced scarring of the liver tissue, regardless of the underlying cause. As the disease progresses, liver cells are destroyed, releasing the mitochondrial form of AST, which was previously protected inside the cell.
A ratio of 2.0 or greater is a highly suggestive finding for alcoholic liver disease (ALD). This disproportionate elevation of AST occurs due to specific reasons related to alcohol metabolism. Chronic alcohol consumption damages the mitochondria within the liver cells, causing a release of the mitochondrial AST form into the bloodstream.
Alcohol abuse can also cause a deficiency in pyridoxal phosphate (Vitamin B6), a co-factor required for ALT production but not as necessary for AST. This functional deficiency effectively lowers the measured ALT level while AST remains high, further skewing the ratio to 2:1 or higher. A ratio exceeding 2.0 provides a strong clinical clue toward an alcohol-related cause, especially if the patient’s Gamma-Glutamyl Transpeptidase (GGT) enzyme level is also elevated.
A high AST/ALT ratio can also be caused by damage originating outside of the liver. Because AST is found in high concentrations in skeletal muscle and the heart, conditions like a recent heart attack, severe muscle injury (rhabdomyolysis), or intense exercise can cause a temporary spike in the AST level. In these non-hepatic scenarios, the elevated AST, combined with a normal or mildly elevated ALT, will artificially produce a ratio greater than 1.0.