Biomarkers of Liver and Gallbladder Function: AST

Optimal Takeaways

The AST enzyme is found in many metabolically active tissues, including the liver, muscle, brain, and pancreas. It facilitates the conversion of amino acids into glucose for energy. Though commonly thought of as a "liver enzyme," its many functions indicate it has much broader applications and should be evaluated in cardiometabolic, musculoskeletal, and inflammatory disorders.

Low levels may be seen in advanced chronic liver disease, kidney disease, ketoacidosis, and vitamin B6 deficiency. Elevated levels suggest the presence of cell and tissue damage with an associated release of AST into the bloodstream. Levels increase with muscle breakdown, heat stroke, trauma, surgery, and inflammatory liver disease. They may increase 10 to 20-fold above the conventional range in the case of acute obstruction outside the liver (e.g., gallstones) or acute hepatitis, respectively.

Standard Range: 10.00 - 35.00 IU/L

The ODX Range: 10.00 - 26.00 IU/L

Low levels of AST may be seen with severe chronic liver disease, uremia, acute kidney disease, chronic hemodialysis, vitamin B6 deficiency, diabetic ketoacidosis, and pregnancy (Pagana 2021).

High levels of AST can be seen with acute trauma, tissue damage, severe burns, surgery, excess exercise, heat stroke, musculoskeletal disease, pancreatitis, hemolytic anemia and other red blood cell disorders, and chronic liver disorders such as hepatitis, cirrhosis, necrosis, drug-induced damage, and liver metastasis. Several drugs can increase AST, including salicylates, opiates, oral contraceptives, antihypertensives, cholinergic agents, digitalis, verapamil, and anticoagulants. Levels of AST can increase due to drug-induced liver injury from statins (Pagana 2021). Elevated AST can also be associated with chronic alcoholism, cardiometabolic risk, NAFLD, and acute myocardial infarction proportional to the degree of heart damage (Ndrepepa 2021).

Overview

Aspartate aminotransferase (AST), previously known as SGOT, is a metabolic enzyme that participates in gluconeogenesis, i.e., the conversion of amino acids into glucose. The AST enzyme transfers amino groups from aspartic acid to ketoglutaric acid to produce oxaloacetic acid. AST is found primarily in muscle and liver cells but also the heart, lung, bone, kidney, pancreas, brain, and red and white blood cells. It is located in the cytoplasm and mitochondria (Lala 2021). AST also maintains the NAD to NADH ratio within cells and glyceroneogenesis, i.e., glycerol generation. Researchers suggest that AST can be used as a reliable marker of general health (Ndrepepa 2021).

Oxidative stress may increase serum AST due to its promotion of mitochondrial damage and cell necrosis. Although often associated with liver and muscle integrity, research suggests increased AST may be related to coronary artery disease (CAD). In one study of 610 individuals being worked up for chest pain, the mean AST was significantly higher at 51 IU/L in those diagnosed with CAD versus 20 IU/L in those without CAD (Shen 2015).

However, the association between AST and cardiovascular disease is complex, as low and high levels have been associated with risk. A study of 6,857 ischemic heart disease patients found a U-shaped curve characterizing the association between AST and cardiac death. An AST below 15 IU/L or above 23 IU/L was associated with increased 3-year cardiac mortality compared to a reference value of 21 IU/L (Ndrepepa 2020). Researchers note that low serum AST can be related to decreased vitamin B6, which in turn is associated with increased cardiovascular risk (Ndrepepa 2021)

A retrospective study of 3,769 Chinese subjects led researchers to update the upper cut-off values for AST from 50 IU/L to 25.35 IU/L for healthy men and 24.25 IU/L for healthy women. Higher levels were associated with higher BMI, alcohol intake, serum cholesterol, and triglycerides (Zhang 2015).

Serum levels of AST can increase as much as 10-fold with an acute obstruction outside of the liver (e.g., gallstones) and as much as 20-fold with acute hepatitis. Levels of AST in cirrhosis depend on how much active inflammation is present. Levels usually come down within 3-7 days with acute damage or injury but can remain persistently elevated in ongoing liver dysfunction (Pagana 2021).

Elevated liver enzymes were associated with abnormal lipid parameters in a cross-sectional study of 23,073 individuals participating in the NHANES study from 1999-2010. The odds of having elevated AST and ALT above conventional range were significantly higher with a low LDL-C below 70 mg/dL (1.81 mmol/L) versus 70-100 mg/dL (1.81-2.59 mmol/L), as well as an HDL-C elevated above 100 mg/dL (2.59 mmol/L) versus 61-80 mg/dL (1.58-2.07 mmol/L) (Jiang 2014).

References

Jiang, Zhenghui Gordon et al. “Low LDL-C and high HDL-C levels are associated with elevated serum transaminases amongst adults in the United States: a cross-sectional study.” PloS one vol. 9,1 e85366. 15 Jan. 2014, doi:10.1371/journal.pone.0085366

Lala, Vasimahmed, et al. “Liver Function Tests.” StatPearls, StatPearls Publishing, 20 August 2021

Ndrepepa, Gjin et al. “Aspartate aminotransferase and mortality in patients with ischemic heart disease.” Nutrition, metabolism, and cardiovascular diseases : NMCD vol. 30,12 (2020): 2335-2342. doi:10.1016/j.numecd.2020.07.033

Ndrepepa, Gjin. "Aspartate aminotransferase and cardiovascular disease—a narrative review." J. Lab. Precis. Med 6.6 (2021).

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Shen, Jianying et al. “Correlation of serum alanine aminotransferase and aspartate aminotransferase with coronary heart disease.” International journal of clinical and experimental medicine vol. 8,3 4399-404. 15 Mar. 2015

Zhang, Peng et al. “Determination of the upper cut-off values of serum alanine aminotransferase and aspartate aminotransferase in Chinese.” World journal of gastroenterology vol. 21,8 (2015): 2419-24. doi:10.3748/wjg.v21.i8.2419