From the Guidelines
For elevated liver enzymes, I recommend a comprehensive laboratory workup including a complete liver panel (ALT, AST, alkaline phosphatase, GGT, bilirubin), complete blood count, and coagulation studies (PT/INR) as the initial step in evaluation, as suggested by the most recent guidelines 1.
Initial Evaluation
The initial evaluation should include a detailed history, inventory of medications, and a physical examination to assess the patient’s risk factors for liver disease, medications, alcohol consumption, comorbid conditions, and signs and symptoms of hepatic disease.
- A complete liver panel is essential to determine the pattern of liver enzyme elevation, which can guide further diagnostic steps.
- Additional important tests include hepatitis serologies (A, B, and C), autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody), iron studies (ferritin, transferrin saturation), ceruloplasmin to rule out Wilson's disease, and alpha-1 antitrypsin levels.
Further Diagnostic Steps
Depending on clinical suspicion, testing for alcohol markers like carbohydrate-deficient transferrin may be appropriate.
- Abdominal ultrasound should accompany these labs to evaluate liver structure and rule out biliary obstruction.
- The pattern of enzyme elevation (hepatocellular vs cholestatic) guides further diagnostic steps, as outlined in the guidelines for the management of abnormal liver blood tests 1.
Considerations
Early identification of the cause of liver enzyme elevation allows for targeted treatment and prevents progression to more severe liver damage.
- The evaluation of patients with elevated serum aminotransferases should exclude common hepatic diseases with noninvasive serologic tests, as recommended by the American Gastroenterological Association 1.
- If these tests are unremarkable, a decision regarding additional serologic testing versus observation should be based on the clinical scenario, taking into account the patient's risk factors, symptoms, and the degree of enzyme elevation.
From the Research
Recommended Labs for Elevated Liver Enzymes
Elevated liver enzymes are a common finding in both symptomatic and asymptomatic patients, necessitating further evaluation to clarify the underlying disease 2. The following labs are recommended:
- Liver function tests, including transaminase activities, alkaline phosphatase, and γ-glutamyltranspeptidase activities
- Ultrasound study to discern intra- from extrahepatic cholestasis
- Screening tests for differential liver diseases, such as viral hepatitis and autoimmune hepatitis
- Non-invasive methods, such as elastography, MRI, MRCP, and CT, may be used to supplement laboratory diagnostics and ultrasound scan
- Invasive methods, such as liver biopsy and ERCP, may be used in selected cases
Patterns of Elevated Liver Enzymes
There are three different patterns of increased liver enzymes:
- A predominant increase in transaminase activities, which reflects a disturbance of hepatocellular integrity and can be found in patients with viral hepatitis, genetic liver diseases, and drug-induced liver diseases 2
- A pattern characterized by high serum alkaline phosphatase and γ-glutamyltranspeptidase activities, indicating cholestatic liver diseases
- A pattern defined by a predominant rise in γ-glutamyl transpeptidase, which is observed in alcoholic or non-alcoholic fatty liver disease and infiltrating liver diseases
Diagnostic Approach
The diagnostic approach to elevated liver function tests should be guided by a detailed medical history and a thorough clinical examination 3. This allows narrowing down possible causes to the few most likely differential diagnoses. Subsequently, depending on the level of elevated liver function and the clinical presentation, screening tests for differential liver diseases are performed.
- A step-wise algorithm can be used to interpret abnormal elevation of liver enzymes in asymptomatic patients 4
- The algorithm classifies enzyme alterations on the basis of pattern (hepatocellular, cholestatic, and isolated hyperbilirubinemia)
- The most common causes of enzyme alteration and initial investigations are reviewed for each pattern
Common Causes of Elevated Liver Enzymes
The most common causes of elevated liver enzymes include: