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AST and ALT are optimal. Why is their ratio high?

The De Ritis ratio refers to the ratio of AST to ALT. It is used to evaluate disease progression, especially liver disease.

Background

The AST:ALT ratio, called the De Ritis ratio, is a tool for monitoring liver dysfunction though it may also be evaluated in muscle damage, ischemic stroke, malignancy, and metabolic syndrome. It is not causative or diagnostic in and of itself.

It is best to monitor the ratio over time and if it increases to 1.5 or above there may be a biliary obstruction, worsening chronic liver disease, or medication-induced hepatoxicity. If it decreases progressively below 1, evaluate for evidence of insulin resistance, metabolic syndrome, and vitamin B6 deficiency.

Hanley, Anthony J G et al. “Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study.” Diabetes vol. 54,11 (2005): 3140-7. doi:10.2337/diabetes.54.11.3140

Rej, R. “Aminotransferases in disease.” Clinics in laboratory medicine vol. 9,4 (1989): 667-87.

Rief, Peter et al. “The AST/ALT (De-Ritis) ratio: A novel marker for critical limb ischemia in peripheral arterial occlusive disease patients.” Medicine vol. 95,24 (2016): e3843. doi:10.1097/MD.0000000000003843

Woreta, Tinsay A, and Saleh A Alqahtani. “Evaluation of abnormal liver tests.” The Medical clinics of North America vol. 98,1 (2014): 1-16. doi:10.1016/j.mcna.2013.09.005

Now for the tricky part. What happens when the AST:ALT ratio is increased but AST and ALT themselves are within range, even within optimal range? As we said, the ratio appears most useful in the presence of disease in order to monitor disease progression, it is not diagnostic by itself.

In one retrospective study of acute ischemic stroke, individuals had AST and ALT levels within an optimal range. However, when the AST:ALT ratio was calculated, researchers found that an AST:ALT ratio of greater than 1.53 on admission was associated with a 1.89-fold increased risk of a poorer outcome 3 months after the stroke.

Interestingly, in this study, those with the lowest AST:ALT ratio and best 3-month prognosis had the highest levels of AST and ALT despite being within optimal range. Researchers note that AST and ALT enzymes are important for clearing glutamate generated after a stroke so that protection may have been compromised in those with lower enzyme levels.

Gao, Fan et al. “De Ritis ratio (AST/ALT) as an independent predictor of poor outcome in patients with acute ischemic stroke.” Neuropsychiatric disease and treatment vol. 13 1551-1557. 15 Jun. 2017, doi:10.2147/NDT.S139316