What to do if Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are elevated?

Management of Elevated AST and ALT Levels

The most appropriate approach for elevated AST and ALT is to conduct a systematic evaluation starting with a detailed history, medication review, and targeted laboratory testing, followed by appropriate management based on the identified cause.

Initial Evaluation

• Obtain a detailed history focusing on risk factors for liver disease, complete medication review (including over-the-counter drugs, vitamins, and herbal supplements), and alcohol consumption history 1, 2
• Assess for symptoms of chronic liver disease such as fatigue, jaundice, and pruritus 2
• Evaluate for metabolic syndrome components (obesity, diabetes, hypertension) as risk factors for nonalcoholic fatty liver disease 2, 1
• Perform physical examination looking for signs of chronic liver disease such as hepatomegaly, jaundice, ascites, and spider angiomata 3

Laboratory Testing

• Order a complete liver panel including AST, ALT, alkaline phosphatase, total and direct bilirubin, albumin, and prothrombin time 1, 2
• Include viral hepatitis serologies (HAV-IgM, HBsAg, HBcIgM, HCV antibody) in the initial evaluation 1, 2
• Consider autoimmune markers (ANA, ASMA, immunoglobulins) if autoimmune hepatitis is suspected 3
• Check thyroid function tests to rule out thyroid disorders as a cause of transaminase elevations 2
• Measure creatine kinase to rule out muscle disorders as a cause of AST elevation (AST is less specific for liver injury) 2, 4

Imaging

• Perform abdominal ultrasound as the first-line imaging test to evaluate for structural causes, biliary obstruction, and hepatic steatosis 2, 3
• Ultrasound has a sensitivity of 84.8% and specificity of 93.6% for detecting moderate to severe hepatic steatosis 2

Management Based on Severity

For Mild Elevations (ALT/AST < 5× ULN)

• Identify and remove potential causative agents, particularly hepatotoxic medications 1, 3
• For nonalcoholic fatty liver disease, implement lifestyle modifications (weight loss, exercise, dietary changes) 2, 3
• For alcoholic liver disease, recommend alcohol cessation and monitor transaminases 2
• For medication-induced liver injury, discontinue suspected hepatotoxic medications when possible 2, 3

For Moderate to Severe Elevations (ALT/AST > 5× ULN)

• Take immediate action including discontinuing all potentially hepatotoxic medications 1, 3
• Perform a more expeditious and complete diagnostic evaluation 1
• Consider referral to a hepatologist 2

Monitoring and Follow-up

• For mild elevations without identified cause, repeat liver enzymes in 2-4 weeks 2, 3
• For identified causes, monitor response to specific interventions 2
• If AST/ALT remains elevated for ≥6 months or if there is evidence of synthetic dysfunction, consider hepatology referral 2, 3
• An AST/ALT ratio <1 is characteristic of nonalcoholic fatty liver disease, viral hepatitis, or medication-induced liver injury 2
• An AST/ALT ratio >2 may suggest alcoholic liver disease or advanced fibrosis 5

Special Considerations

• Normal ALT ranges differ by sex: 29-33 IU/L for males and 19-25 IU/L for females 2
• AST is less specific for liver injury and can be elevated in cardiac and skeletal muscle disorders 2, 4
• Isolated AST elevation without other abnormalities may indicate macro-AST, a benign condition that can be confirmed with polyethylene glycol precipitation test 6
• Do not ignore mild, persistent elevations, as they warrant thorough evaluation if persisting beyond 6 months 3
• Do not attribute all elevations to fatty liver without excluding other causes 3, 7

By following this systematic approach, you can effectively identify and manage the underlying cause of elevated AST and ALT levels, improving patient outcomes and preventing progression of liver disease.