What is the management and follow-up for elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels?

From the Guidelines

Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels indicate liver injury, and management involves identifying and addressing the underlying cause.

Initial Evaluation

The initial evaluation of patients with elevated AST and ALT levels should include noninvasive serologic tests to exclude common hepatic diseases 1.

• If these tests are unremarkable, a decision regarding additional serologic testing versus observation should be based on the clinical scenario.
• If one elects observation, close clinical follow-up and serial serum liver chemistry testing is essential 1.

Follow-up and Monitoring

Follow-up liver function tests (LFTs) should be performed at 6-8 weeks after initiation of treatment, and then every 3-6 months to monitor for improvement or worsening of liver enzymes 1.

• In cases where weekly intervals for monitoring at the study site are challenging, use of local labs may be considered 1.
• The frequency of liver test monitoring may be reduced in later phase clinical trials guided by the risk of hepatotoxicity and liver status 1.

Further Evaluation

If AST/ALT levels remain elevated, further evaluation with imaging studies and/or liver biopsy may be necessary to guide additional treatment 1.

• Chronic ALT or AST elevations (6 or more months) usually warrant additional serologic and radiologic evaluations and potentially a liver biopsy 1.
• Liver biopsy may be considered in patients with chronic HCV viremia and either normal or abnormal serum ALT levels 1.

From the Research

Management and Follow-up for Elevated AST and ALT Levels

The management and follow-up for elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels involve a stepwise evaluation to determine the underlying cause of the elevation.

• The most common cause of mildly elevated transaminase levels is nonalcoholic fatty liver disease, which can affect up to 30 percent of the population 2.
• Other common causes include alcoholic liver disease, medication-associated liver injury, viral hepatitis (hepatitis B and C), and hemochromatosis 2.
• Initial testing should include a fasting lipid profile; measurement of glucose, serum iron, and ferritin; total iron-binding capacity; and hepatitis B surface antigen and hepatitis C virus antibody testing 2.
• If test results are normal, a trial of lifestyle modification with observation or further testing for less common causes is appropriate 2.

Predictive Value of AST and ALT

• Elevated AST levels indicate a high specificity and a reasonable sensitivity for liver injury 3.
• AST is a better predictor of all-cause and liver-related mortality than ALT 4.
• Elevated AST levels are associated with an increased risk of liver-specific mortality, as well as non-hepatic diseases including diabetes mellitus type 2, metabolic syndrome, cardiovascular diseases, and malignancies 3, 4.
• The AST to ALT ratio can be used to predict acute kidney injury after cardiac surgery, with a higher ratio associated with an increased incidence of postoperative acute kidney injury 5.

Clinical Characteristics and Outcome

• Abnormal liver function tests, including elevated AST and ALT levels, are frequent in acute heart failure and predict worse outcomes 6.
• The prevalence of abnormal liver function tests in acute heart failure patients is high, with 20% having elevated AST levels and 12% having elevated ALT levels at baseline 6.
• Abnormal liver function tests at baseline are associated with a higher risk of in-hospital death and 180-day mortality 6.