The De Ritis ratio is a simple but powerful tool used in clinical assessment, primarily to evaluate the potential cause and extent of liver damage. Named after Fernando De Ritis who first described it in 1957, this metric is derived from two common enzymes measured in routine blood work. The ratio represents the relationship between these two enzyme concentrations, which change depending on the type and severity of an underlying condition. Its utility lies in helping differentiate between various liver disorders, offering non-invasive diagnostic clues about the location and nature of cell injury.
The Individual Components: AST and ALT
The De Ritis ratio uses the serum activities of Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT), enzymes involved in amino acid metabolism. These enzymes are normally contained within cells; their presence in the bloodstream indicates that cells have been damaged and leaked their contents.
ALT is primarily concentrated within the liver, making it a more specific indicator of liver cell injury and inflammation. When liver cells (hepatocytes) are damaged, such as by viral infection or fat accumulation, ALT leaks into the blood quickly. A significantly elevated ALT level is therefore a strong signal of hepatocellular damage.
AST is abundant in the liver but also found in significant quantities in other tissues, including the heart, skeletal muscle, kidneys, and brain. This wider distribution means an elevated AST level alone is less specific to the liver, potentially signaling injury to a non-hepatic organ like the heart. Furthermore, within liver cells, ALT is located almost exclusively in the cytoplasm, while AST is found in both the cytoplasm and the mitochondria.
How the De Ritis Ratio is Calculated and Generally Interpreted
The De Ritis ratio, also known as the AST/ALT ratio, is calculated by dividing the serum concentration of AST by the concentration of ALT. This calculation produces a dimensionless number that helps interpret the relative balance of the two enzymes, providing context that individual values alone might miss. In healthy individuals, the ratio typically falls around 1.0, though reference ranges can vary slightly between laboratories, often spanning from about 0.7 to 1.5.
A ratio outside this range suggests an imbalance in enzyme release, pointing toward different mechanisms of cellular injury. When the ratio is low (generally less than 1.0), ALT is the dominant enzyme in the blood. Since ALT is highly specific to the liver, a low ratio often suggests a less severe or chronic form of liver damage, where the injury is contained largely within the cell cytoplasm.
Conversely, an elevated ratio (AST dominant) suggests a different pattern of damage. The higher ratio may indicate that the injury is more acute or severe, potentially involving the mitochondria of the liver cells where the second pool of AST is located. Alternatively, a high ratio can signal that the elevated AST originates from non-liver sources, such as the heart or skeletal muscles.
Diagnostic Patterns and Clinical Significance
The De Ritis ratio is a valuable tool for differentiating between various liver diseases because specific conditions produce characteristic ratios. A ratio significantly greater than 1.5, and especially 2.0 or higher, is highly suggestive of Alcoholic Liver Disease (ALD). This disproportionate elevation of AST in ALD occurs because alcohol damages liver cell mitochondria, causing a massive release of the mitochondrial AST pool.
Alcohol abuse also leads to a deficiency of Vitamin B6 (pyridoxal phosphate), a necessary cofactor for ALT synthesis, which further suppresses the ALT level. A high ratio is also frequently observed in advanced stages of liver disease, such as cirrhosis, regardless of the underlying cause. This happens because the reduced number of healthy liver cells cannot efficiently clear AST from the bloodstream.
In contrast, a low ratio (typically less than 1.0) is most commonly seen in conditions like acute viral hepatitis, Non-Alcoholic Fatty Liver Disease (NAFLD), and Non-Alcoholic Steatohepatitis (NASH). In these cases, the injury targets the cytoplasm of the liver cells, resulting in a significantly higher release of the liver-specific ALT. For example, in acute viral hepatitis, the ratio is often well below 1.0, sometimes ranging from 0.5 to 0.7.
The ratio can also serve as a prognostic indicator; an increasing ratio in chronic conditions like viral hepatitis often suggests progression toward fibrosis and cirrhosis. However, the ratio’s interpretation must always be tempered by the total enzyme levels. If both AST and ALT are only mildly elevated, the ratio is less reliable, and if levels are extremely high (in the thousands), it usually points toward a massive acute injury like ischemic hepatitis.