Understanding High AST Levels: Causes and Implications

Aspartate aminotransferase (AST) is an enzyme concentrated in the liver. It becomes elevated in response to tissue damage or disease, making it a valuable biomarker for liver health. According to the Centers for Disease Control and Prevention, liver disease affects approximately 4.5 million adults in the United States, highlighting the importance of AST in early detection and intervention. 

However, AST is also found in other tissues, and elevated AST levels can signal a range of issues, from heart disease to muscle disorders. Understanding the causes, implications, and diagnostic processes associated with high AST levels makes health and diagnostic evaluations more efficient. 

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What Is AST?

Aspartate aminotransferase (AST) is an enzyme found primarily in the liver, heart, and skeletal muscles, but it is also present in smaller amounts in other tissues and organs, such as the pancreas and kidneys. It helps process proteins by moving a part of aspartate, an amino acid, to alpha-ketoglutarate, creating oxaloacetate and glutamate. Oxaloacetate enters the Krebs cycle – also known as the citric acid or TCA cycle – a series of reactions that produce energy (called ATP) for our cells. (4) 

AST is significant because elevated levels in the blood can indicate tissue damage or disease. Under normal conditions, AST levels in the blood are low. However, when cells in organs where AST is abundant are damaged, AST is released into the bloodstream, causing elevated levels. This is why AST is often measured in blood tests as a marker for liver health. (4, 17) 

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Normal Results

Reference ranges for AST are listed below. Normal values may vary slightly between different laboratories. Age and gender will influence normal ranges. 

Children:

• 0-5 days: 35-140 U/L
• < 3 years: 15-60 U/L
• 3-6 years: 15-50 U/L
• 6-12 years: 10-50 U/L
• 12-18 years: 10-40 U/L

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Adults: 0-35 U/L (values tend to be slightly lower in females than males)

Elderly: Values are slightly higher than those of other adults

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Causes of High AST Levels

AST is a non-specific marker, meaning that elevated levels in the blood can indicate damage or disease in a variety of tissues, not just a single organ. Since AST is present in the liver, heart, muscles, kidneys, and brain, an increase in its levels could result from conditions affecting any of these tissues. 

Liver Conditions

Hepatitis is a medical condition characterized by inflammation of the liver, which can impair its function and lead to various health complications. It can be caused by viral infections (hepatitis viruses A, B, C, D, and E), metabolic disorders, excessive alcohol consumption, exposure to certain medications and toxins, and autoimmune disease.

‍Non-alcoholic fatty liver disease (NAFLD) is a condition characterized by the accumulation of excess fat in the liver cells of people who consume little to no alcohol. It is a spectrum of liver diseases that ranges from simple steatosis (fat accumulation without significant inflammation or liver damage) to non-alcoholic steatohepatitis (NASH), which includes inflammation and can progress to fibrosis, cirrhosis, and liver failure. NAFLD is commonly associated with metabolic syndrome, obesity, insulin resistance, type 2 diabetes, and dyslipidemia. (42) 

Cirrhosis is a late-stage chronic liver disease characterized by scarring (fibrosis) of liver tissue, leading to impaired liver structure and function. 

Liver cancer originates in the liver cells and is most commonly classified as hepatocellular carcinoma (HCC). Other types, such as cholangiocarcinoma and hepatoblastoma, are less common. Risk factors for liver cancer include chronic viral hepatitis, cirrhosis, NAFLD, aflatoxin (a toxic substance produced by certain molds) exposure, and excessive alcohol consumption.

Heart Conditions

Myocardial infarction (MI), more commonly known as a heart attack, occurs when blood flow to a part of the heart muscle is blocked for an extended period, leading to damage or death of the heart tissue. This blockage is typically caused by the buildup of plaque in the coronary arteries, resulting in the rupture of the plaque and the formation of a blood clot. In an acute MI, AST will begin to elevate 6-8 hours after symptom onset, reach peak levels at 24-36 hours, and return to baseline in 3-7 days.

Elevated AST can be measured in other forms of heart disease, including congestive heart failure (CHF) and myocarditis.

Muscle Disorders

Muscle injury or trauma can result in either transient elevations of AST in cases of acute injury or sustained elevations in chronic injury or inflammation. Examples include:

• Exercise
• Rhabdomyolysis (a serious condition where damaged muscles release proteins and electrolytes into the bloodstream)
• Muscular dystrophy (a group of genetic disorders causing progressive muscle weakness and loss of muscle mass)
• Polymyositis (a rare inflammatory disease that causes muscle weakness and inflammation)

Other Causes

Other causes of elevated AST levels include: 

• Pancreatitis
• Hemochromatosis 
• Mononucleosis
• Seizure
• Hemolysis (destruction of red blood cells) 
• Surgery
• Pregnancy
• Medications, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors, nicotinic acid, isoniazid, sulfonamides, erythromycin, and antifungals  

Symptoms and Health Implications

Symptoms experienced by patients with elevated AST can vary depending on the underlying cause. 

In cases related to liver disease, symptoms may include: 

• Jaundice (a yellowing of the skin and eyes)
• Fatigue
• Abdominal pain
• Ascites (abdominal fluid accumulation)
• Itching
• Light colored stools
• Dark urine
• Weight loss

When liver disease goes untreated, it can progress to end-stage liver disease and liver failure. Complications of portal hypertension and liver cancer are the leading causes of hospitalization and death in people with liver failure. (32) 

Cardiovascular disease, which encompasses coronary artery disease (CAD), peripheral artery disease (PAD), heart attack, heart failure, and stroke, is responsible for one in five deaths in the United States, making it the leading cause of death. Patients with cardiovascular conditions that manifest with elevated AST levels may report:

• Chest pain
• Shortness of breath
• Claudication (pain in the arms or legs that occurs with walking) 
• Edema
• Dizziness
• Irregular heartbeat 

Muscle weakness and pain are the most common symptoms of myopathies. Untreated muscle disorders will lead to progressive muscle weakness and reduced mobility.

Diagnosis and Evaluation

AST's nonspecificity necessitates the use of additional tests and clinical information to accurately diagnose the underlying cause of elevated AST levels. 

Medical History and Physical Examination

Patient evaluation should begin with gathering a detailed patient history and conducting a thorough physical examination to identify potential causes of elevated AST. 

Doctors should ask patients about: 

• Recent trauma
• Alcohol use
• Risk factors for viral hepatitis, including IV drug use, exposure to non-sterile needles, and blood transfusions
• Supplements and medications 
• Diet and exercise 
• Symptoms of liver, heart, and muscle disease

A comprehensive physical exam should include the following components:

• Vitals
• Cardiovascular
• Pulmonary
• Abdominal
• Skin

Other Lab Tests and Biomarkers

Obtain a complete hepatic function panel, including: 

• Alanine aminotransferase (ALT)
• Alkaline phosphatase (ALP)
• Gamma-glutamyl transferase (GGT)
• Bilirubin 
• Lactate dehydrogenase (LDH)

Liver disease often manifests with abnormal findings of multiple liver biomarkers. Specific patterns can help narrow the differential diagnosis. For example: 

• Acute viral hepatitis or acetaminophen toxicity are likely when aminotransferase levels are greater than 500 U/L.
• An AST:ALT ratio greater than 2 is indicative of alcoholic liver disease.
• AST and ALT are typically 7-10 times the upper limit of normal in autoimmune hepatitis.

A serum AST:ALT ratio greater than 5 indicates extrahepatic injury, especially if ALT is normal. Additional tests to investigate for extrahepatic causes of elevated AST include: 

• Creatine kinase when muscle damage is suspected
• Cardiac enzymes, including troponin and natriuretic peptides, to evaluate for heart conditions 
• Comprehensive metabolic panel (CMP) to assess blood glucose and kidney function
• Thyroid panel to rule out thyroid disorders
• Celiac antibodies to rule out celiac disease

Imaging Studies

Liver enzymes will normalize after 2-4 weeks in about one-third of people with elevated liver enzymes. If your enzymes stay high, your doctor will likely order imaging tests, such as ultrasound, CT scan, or MRI, to evaluate further. Sometimes, a liver biopsy is also indicated for diagnosing liver conditions.

Treatment and Management

The course of treatment for elevated AST is dependent on the underlying cause. Examples may include: 

• Eating an anti-inflammatory diet and exercising at least 150 minutes weekly to support liver and heart health. 
• Discontinue alcohol and hepatotoxic medication use
• Lose weight (if overweight)
• Treat diabetes, high blood pressure, and high cholesterol (if conditions are present)
• Take liver-supporting supplements, such as milk thistle, turmeric, and dandelion root, to counteract liver damage and combat oxidative stress.
• Take supplements that support the cardiovascular system, such as hawthorn berry, garlic, omega-3 fatty acids, and magnesium.
• In some cases, doctors will prescribe medications to manage underlying health conditions. These should be taken as prescribed. 

Guidelines typically recommend remeasuring liver enzymes in 1 to 3-month increments to monitor. Additional tests or imaging should be ordered, as necessary, if AST levels do not normalize. 

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Key Takeaways

• Aspartate aminotransferase (AST) is an enzyme commonly used as a biomarker for liver health, but elevated levels in blood tests can indicate various underlying health conditions, including liver disease, heart conditions, and muscle disorders. 
• Diagnosis involves a comprehensive approach, utilizing medical history, physical examination, additional tests, and imaging studies to identify the specific cause. 
• Treatment strategies depend on the underlying condition, and they can range from lifestyle modifications to medications. Early intervention and regular follow-ups can prevent progression to more serious health complications and improve long-term outcomes.