What tests to order when Alanine Transaminase (ALT) and Aspartate Transaminase (AST) are elevated?

From the Guidelines

When both ALT and AST are elevated, further testing should focus on identifying the underlying cause of liver injury, starting with a comprehensive metabolic panel, complete blood count, and coagulation studies (PT/INR) to assess liver function and rule out acute liver failure, as recommended by the most recent guidelines 1.

Initial Steps

The initial steps in evaluating elevated ALT and AST include:

• Ordering viral hepatitis serologies, including hepatitis A, B, and C
• Testing for autoimmune markers such as antinuclear antibody, anti-smooth muscle antibody, and immunoglobulin levels to evaluate for autoimmune hepatitis
• Considering iron studies, ceruloplasmin, and alpha-1 antitrypsin levels to rule out hereditary conditions

Imaging and Additional Tests

Abdominal ultrasound is essential to evaluate liver structure, identify fatty infiltration, and assess for biliary obstruction or masses. If alcohol use is suspected, checking gamma-glutamyl transferase (GGT) is recommended. For patients with risk factors, testing for non-alcoholic fatty liver disease is also necessary.

Diagnostic Clues

The pattern of elevation (AST:ALT ratio) can provide diagnostic clues:

• A ratio >2 suggests alcoholic liver disease
• A ratio <1 is more common in viral hepatitis and non-alcoholic fatty liver disease
• The degree of elevation also matters, with values >1000 U/L suggesting acute viral hepatitis, drug-induced liver injury, or ischemic hepatitis, as discussed in the guidelines 1.

Key Considerations

It is crucial to consider the degree of variation that exists for ALT reference ranges between laboratories and to determine baseline ALT levels accurately, taking into account the fluctuations that can occur in patients with nonalcoholic steatohepatitis (NASH) 1.

From the Research

Evaluation of Elevated ALT and AST

When ALT and AST are elevated, it is essential to investigate the underlying cause. The following are potential tests to consider:

• Liver function tests: Repeat ALT and AST measurements to confirm the elevation and monitor for any changes over time 2, 3.
• Viral hepatitis screening: Test for hepatitis B and C viruses, as these are common causes of elevated liver enzymes 2, 3, 4.
• Imaging studies: Consider hepatic ultrasonography to evaluate for liver damage or disease 5.
• Autoimmune hepatitis testing: Measure IgG levels and consider a liver biopsy to evaluate for autoimmune hepatitis, especially in patients with cirrhosis 6.
• Metabolic syndrome evaluation: Assess for metabolic syndrome and insulin resistance by measuring waist circumference, blood pressure, fasting lipid level, and fasting glucose or A1C level 5.
• Complete blood count: Perform a complete blood count with platelets to evaluate for extrahepatic causes of elevated liver enzymes, such as hemolysis or muscle disorders 5.
• Serum albumin, iron, total iron-binding capacity, and ferritin measurements: Evaluate for hereditary hemochromatosis or other iron-related disorders 5.

Potential Causes of Elevated ALT and AST

The following are potential causes of elevated ALT and AST:

• Chronic hepatitis C: Elevated ALT and AST levels are common in patients with chronic hepatitis C 2, 3, 4.
• Non-alcoholic steatohepatitis (NASH): NASH is a common cause of elevated liver enzymes, especially in patients with metabolic syndrome 3, 5.
• Alcoholic liver disease: Alcoholic liver disease can cause elevated ALT and AST levels, especially in patients with a history of excessive alcohol consumption 3, 5.
• Autoimmune hepatitis: Autoimmune hepatitis can cause elevated liver enzymes, especially in patients with cirrhosis 6.
• Drug-induced liver injury: Certain medications can cause elevated liver enzymes, and a thorough medication history should be obtained 5.
• Hereditary hemochromatosis: Hereditary hemochromatosis is a rare cause of elevated liver enzymes, but it should be considered in patients with a family history of the disease 5.
• Alpha1-antitrypsin deficiency: Alpha1-antitrypsin deficiency is a rare cause of elevated liver enzymes, but it should be considered in patients with a family history of the disease 5.
• Wilson disease: Wilson disease is a rare cause of elevated liver enzymes, but it should be considered in patients with a family history of the disease 5.
• Thyroid disorders: Thyroid disorders, such as hypothyroidism, can cause elevated liver enzymes 5.
• Celiac sprue: Celiac sprue is a rare cause of elevated liver enzymes, but it should be considered in patients with a history of gastrointestinal symptoms 5.
• Hemolysis: Hemolysis can cause elevated liver enzymes, especially in patients with a history of hemolytic anemia 5.
• Muscle disorders: Muscle disorders, such as polymyositis, can cause elevated liver enzymes 3, 5.