What is the management approach for patients with elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) lab values?

From the Guidelines

Management of patients with elevated AST and ALT lab values should begin with a comprehensive evaluation to determine the underlying cause, including a detailed medical history, physical examination, and laboratory testing, as recommended by the most recent guidelines 1. The initial steps in managing elevated AST and ALT include:

• Obtaining a detailed medical history focusing on medication use, alcohol consumption, and risk factors for viral hepatitis
• Physical examination looking for signs of chronic liver disease
• Laboratory testing, including a complete metabolic panel, complete blood count, coagulation studies, and specific tests for viral hepatitis (HBV, HCV), autoimmune hepatitis, hemochromatosis, Wilson's disease, and alpha-1 antitrypsin deficiency The severity of abnormal aminotransferase can be classified as mild, moderate, or severe, with moderate and severe elevations requiring more expeditious evaluations 1. Imaging studies such as ultrasound, CT, or MRI may be necessary to evaluate liver structure, and management is cause-specific, including discontinuing hepatotoxic medications, abstaining from alcohol, antiviral therapy for viral hepatitis, weight loss and exercise for non-alcoholic fatty liver disease, and immunosuppressive therapy for autoimmune hepatitis 1. Supportive care includes maintaining adequate nutrition and avoiding additional liver insults, and patients with severe liver dysfunction may require hospitalization, while those with mild to moderate elevations can often be managed as outpatients with regular monitoring of liver enzymes every 2-4 weeks until improvement 1. Referral to a hepatologist is recommended for persistent unexplained elevations or evidence of advanced liver disease, and the most recent guidelines emphasize the importance of a comprehensive evaluation and cause-specific management 1.

From the FDA Drug Label

Increases in serum transaminases have been reported with use of ezetimibe tablets [see Adverse Reactions (6.1)]. Perform liver enzyme testing as clinically indicated and consider withdrawal of ezetimibe tablets if increases in ALT or AST ≥3 X ULN persist.

The management approach for patients with elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) lab values is to:

• Perform liver enzyme testing as clinically indicated
• Consider withdrawal of ezetimibe tablets if increases in ALT or AST ≥3 X ULN persist 2
• Monitor liver enzyme levels to ensure patient safety 2
• Be aware of the potential for myopathy and rhabdomyolysis, especially when used in combination with a statin or other LDL-C lowering therapies 2

From the Research

Management Approach for Elevated AST and ALT Lab Values

The management approach for patients with elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) lab values involves a comprehensive evaluation to determine the underlying cause of the elevation.

• The initial evaluation should include an assessment for metabolic syndrome and insulin resistance, as well as testing for common causes of elevated transaminase levels, such as nonalcoholic fatty liver disease and alcoholic liver disease 3.
• The nonalcoholic fatty liver disease fibrosis score and the alcoholic liver disease/nonalcoholic fatty liver disease index can be helpful in the evaluation of mildly elevated transaminase levels 3.
• If testing for common causes is consistent with nonalcoholic fatty liver disease and is otherwise unremarkable, a trial of lifestyle modification is appropriate 3.
• If the elevation persists, hepatic ultrasonography and further testing for uncommon causes, such as drug-induced liver injury, hepatitis B and C, and hereditary hemochromatosis, should be considered 3.

Causes of Elevated AST and ALT Lab Values

Elevated AST and ALT lab values can be caused by a variety of factors, including:

• Chronic alcohol consumption 4
• Non-alcoholic steatohepatitis (NASH) 4
• Chronic viral hepatitis 4
• Polymyositis 4
• Acute muscle injury 4
• Acute myocardial infarction 4
• Hypothyroidism 4
• Drug-induced liver injury 3
• Hepatitis B and C 3
• Hereditary hemochromatosis 3

Diagnostic Utility of AST and ALT

AST and ALT are useful markers for liver disease, and their levels can be used to diagnose and assess liver damage 5, 6.

• The AST/ALT ratio can be used to predict cirrhosis, with a ratio of ≥1 being highly suggestive of the presence of cirrhosis 5.
• Low-cost point-of-care monitoring of ALT and AST is promising for faster decision making and diagnosis of acute liver injury 6.