How to manage elevated AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) levels?

From the Guidelines

Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels indicate liver injury, and treatment should be guided by the underlying cause.

Causes of Elevated AST and ALT

The causes of elevated AST and ALT can be categorized into several groups, including:

• Viral hepatitis: treatment with antiviral medications such as entecavir (0.5-1 mg daily) or tenofovir (300 mg daily) for a duration of 48-96 weeks 1
• Drug-induced liver injury: discontinuation of the offending agent, and in severe cases, administration of N-acetylcysteine (150 mg/kg loading dose, followed by 100 mg/kg every 4 hours for 24 hours) 1
• Autoimmune hepatitis: treatment with immunosuppressive medications, such as prednisone and azathioprine 1

Management of Elevated AST and ALT

The management of elevated AST and ALT involves:

• Monitoring liver function tests: regular monitoring of AST, ALT, and bilirubin levels to assess the severity of liver injury and response to treatment 1
• Avoiding hepatotoxic substances: patients with elevated AST and ALT levels should be advised to avoid alcohol and other hepatotoxic substances 1
• Workup for other causes: workup for other causes of elevated liver enzymes, such as viral hepatitis, alcohol history, iron studies, thromboembolic event, or potential liver metastasis from primary malignancy 1

Key Points

• Elevated AST and ALT levels indicate liver injury and require prompt evaluation and treatment
• Treatment should be guided by the underlying cause of liver injury
• Monitoring liver function tests and avoiding hepatotoxic substances are essential components of management
• Workup for other causes of elevated liver enzymes is necessary to rule out other potential causes of liver injury 1

From the FDA Drug Label

Among entecavir-treated subjects in these studies, on-treatment ALT elevations greater than 10 times the upper limit of normal (ULN) and greater than 2 times baseline generally resolved with continued treatment. Periodic monitoring of hepatic function is recommended during treatment.

Management of Elevated AST and ALT Levels:

• Continue treatment: On-treatment ALT elevations generally resolve with continued treatment.
• Monitor hepatic function: Periodic monitoring of hepatic function is recommended during treatment.
• No specific dose adjustment: The provided drug labels do not specify dose adjustments for elevated AST and ALT levels.
• Caution with treatment discontinuation: Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir. Hepatic function should be monitored closely for at least several months after discontinuation 2, 2.

From the Research

Causes of Elevated AST and ALT Levels

• Chronic alcohol consumption, drugs, non-alcoholic steatohepatitis (NASH), and chronic viral hepatitis are common causes associated with raised ALT and AST 3
• Non-hepatic causes of raised ALT and AST include polymyositis, acute muscle injury, acute myocardial infarction, and hypothyroidism 3
• Drug-induced liver injury (DILI) is a significant cause of elevated ALT levels, with antibacterials and glucocorticoids being the most common agents causing DILI 4
• COVID-19 infection can also cause liver injury, with various pathogenic mechanisms such as hepatotoxicity, SARS-CoV-2 infection of bile duct cells and hepatocytes, hypoxia, and systemic inflammatory response 5

Management of Elevated AST and ALT Levels

• In the primary care setting, the doctor should obtain a complete history regarding risk factors for viral hepatitis, substance abuse, and request investigations accordingly 3
• Suspected chronic viral hepatitis and liver cirrhosis are best referred to a hepatologist for further management 3
• For DILI, treatment includes anti-inflammatory drugs, antioxidants, polyene phosphatidylcholine, and herbal extracts 4
• Monitoring of liver biochemistry tests such as AST, ALT, gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) is essential in COVID-19 patients with liver injury 5

Prognostic Value of AST and ALT Levels

• Elevated AST levels are a better predictor of all-cause and liver-related mortality than ALT levels 6
• Elevated AST levels can result in a loss of life expectancy by 10 years or more 6
• AST levels are also a significant predictor of mortality from all cancers, stroke, respiratory diseases, and injuries, other than just liver disease 6
• Elevated serum transaminases in patients with acute coronary syndromes may not necessarily indicate liver disease and may lead to excessive exclusions from clinical trials 7