The ratio of AST to ALT can provide information about worsening liver fibrosis, muscle and tissue damage, and cardiovascular and cerebrovascular risk, even if the individual biomarkers are within range. The ratio can increase significantly as liver fibrosis or severe muscle damage occurs and should be assessed further, including a hepatobiliary and cardiometabolic evaluation.
Standard Range: 0.00 - 1.00 Ratio
The ODX Range: 0.00 - 1.00 Ratio
Low AST: ALT ratio may be associated with insulin resistance and increased risk of metabolic syndrome (Gao 2017).
High AST:ALT ratio may be associated with worsening fibrosis in liver disease, ischemic or toxic liver insult, hepatitis (Kasaral 2016), alcoholic liver disease, cirrhosis, Wilson’s disease (Hall 2012), cardiovascular risk, ischemic heart damage and MI (Steininger 2018), peripheral artery disease, critical limb ischemia (Rief 2016), all-cause mortality in hypertensives (Kiu 2021), stroke severity (Wang 2020, Gao 2017), prostate cancer (Zhou 2020), other types of cancer, and all-cause mortality (Chen 2022).
The ratio of AST to ALT, known as the De Ritis ratio, is used to monitor the progression and severity of known liver disease, biliary obstruction, muscle damage, and even cardiovascular risk. Though many liver complications increase ALT, which would decrease the AST:ALT ratio, ischemic or toxic insults predominantly increase AST, increasing the ratio. A ratio rising above 1 in liver disease can be seen with advancing fibrosis and scarring due to tissue damage. Alcoholic hepatitis is associated with increased AST and a De Ritis ratio of 2. An AST:ALT ratio above 1.5 in viral hepatitis may indicate a quick progression of liver dysfunction (Kasarala 2016). A value above 1 is seen in 92% of alcoholic liver disease and climbs above 2 in 70% of cases. While an AST:ALT ratio above 1 suggests cirrhosis, it is not diagnostic by itself. Cirrhosis is more likely with a De Ritis ratio above 1, a platelet count below 150,000 10E3/uL, and a longer blood clotting time, i.e., higher prothrombin time. In acute liver failure, an elevated AST:ALT ratio above 2.2, along with an alkaline phosphatase:bilirubin ratio below 4, indicates Wilson’s disease (Hall 2012).
A higher De Ritis ratio is associated with cardiac risk and can be 2.0 or higher with coronary occlusion. The ratio was significantly higher at 3.2 in myocardial infarction patients with an ST-segment elevation versus 2.2 in those with a non-ST-segment elevation (Djakpo 2020).
The ratio helps predict prognosis in acute MI as well. In one study of 1,355 MI patients, AST:ALT was strongly correlated with elevations in troponin-T values, creatine kinase, NT-pro-BNP, and CRP at baseline, as well as long-term mortality, especially cardiovascular mortality, at follow-up. Those with the worst survival had a De Ritis ratio of 3.6, while those with the best survival had a ratio of 0.8. Researchers note that AST is abundant in cardiac tissue and released during ischemic heart damage. Statin therapy did not influence the ratio’s predictive potential (Steininger 2018).
A cohort study of 14,220 Chinese hypertensives found that the highest AST:ALT ratio, above 1.6, was associated with a significantly increased risk of all-cause and cardiovascular mortality compared to the lowest ratio of 1.2 or below (Liu 2021). A higher AST:ALT ratio was also associated with stroke severity. In a study of 2,042 patients with ischemic stroke, an AST:ALT ratio of 1.22 or above was an independent risk factor for hemorrhagic transformation, a severe complication (Wang 2020).
The prognosis following stroke may also be evaluated using the De Ritis ratio. Both AST and ALT may be neuroprotective and reduce the circulating glutamate that increases following stroke. A retrospective study of 421 acute ischemic stroke patients found that those with the poorest outcome had the highest De Ritis ratio. Researchers note that a baseline ratio greater than 1.53 was independently associated with a 1.89-fold greater risk of poor outcomes at three months. Interestingly, those with the highest De Ritis ratio and poorest prognosis had the lowest median levels of AST and ALT at 18.1 IU/L and 15.7 IU/L, respectively, levels within the optimal range, emphasizing the utility of calculating the ratio (Gao 2017).
Elevated AST can reflect muscle damage and critical limb ischemia due to peripheral artery disease, which was more likely with a De Ritis ratio of 1.67 or above in a cross-sectional study of 1,782 patients. Levels of CRP and fibrinogen were also significantly elevated in the group with a higher ratio versus below 1.67 (Rief 2016). Skeletal muscle damage can greatly increase the ratio, especially if ALT is normal or slightly elevated. A ratio above 5 suggests rhabdomyolysis or strenuous exercise (Woreta 2014).
The AST:ALT ratio was also significantly higher in patients with prostate cancer compared to benign prostatic hyperplasia (BPH). Researchers recommend a De Ritis ratio cut-off of 1.55 and above to predict the incident risk of prostate cancer. However, it did not differentiate between high-risk and low-risk disease (Zhou 2020).
Evaluation of AST:ALT differs in insulin resistance. A lower De Ritis ratio is associated with increased insulin resistance, especially as BMI increases. A review of NHANES data from 2,747 individuals with normal ALT found a 75% greater risk of insulin resistance with the lowest quartile of AST:ALT (less than 1.12 in women and less than 0.93 in men) compared to the highest quartile (1.47 or higher in women and 1.26 or greater in men) (Visaria 2022). Further evaluation of cardiometabolic health should help interpret De Ritis ratio values.
Chen, Wangyang et al. “Elevated AST/ALT ratio is associated with all-cause mortality and cancer incident.” Journal of clinical laboratory analysis vol. 36,5 (2022): e24356. doi:10.1002/jcla.24356
Djakpo, Dodji Kossi et al. “The significance of transaminase ratio (AST/ALT) in acute myocardial infarction.” Archives of medical sciences. Atherosclerotic diseases vol. 5 e279-e283. 26 Dec. 2020, doi:10.5114/amsad.2020.103028
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
Hall P, Cash J. What is the real function of the liver 'function' tests? Ulster Med J. 2012 Jan;81(1):30-6.
Kasarala, George, and Hans L Tillmann. “Standard liver tests.” Clinical liver disease vol. 8,1 13-18. 26 Jul. 2016, doi:10.1002/cld.562
Liu, Hui et al. “The association between AST/ALT ratio and all-cause and cardiovascular mortality in patients with hypertension.” Medicine vol. 100,31 (2021): e26693. doi:10.1097/MD.0000000000026693
Rief P, Pichler M, Raggam R, et al. The AST/ALT (De-Ritis) ratio: A novel marker for critical limb ischemia in peripheral arterial occlusive disease patients. Medicine (Baltimore). 2016 Jun;95(24):e3843.
Steininger, Matthias et al. “De-Ritis Ratio Improves Long-Term Risk Prediction after Acute Myocardial Infarction.” Journal of clinical medicine vol. 7,12 474. 23 Nov. 2018, doi:10.3390/jcm7120474
Visaria, Aayush et al. “Association between aspartate aminotransferase-to-alanine aminotransferase ratio and insulin resistance among US adults.” European journal of gastroenterology & hepatology vol. 34,3 (2022): 316-323. doi:10.1097/MEG.0000000000002215
Wang, Yanan et al. “AST to ALT ratio and risk of hemorrhagic transformation in patients with acute ischemic stroke.” Neurological research vol. 42,11 (2020): 980-986. doi:10.1080/01616412.2020.1796403
Woreta TA, Alqahtani SA. Evaluation of abnormal liver tests. Med Clin North Am. 2014 Jan;98(1):1-16.
Zhou, Jiatong et al. “AST/ALT ratio as a significant predictor of the incidence risk of prostate cancer.” Cancer medicine vol. 9,15 (2020): 5672-5677. doi:10.1002/cam4.3086