From the Guidelines
The initial workup for a patient with mildly elevated liver enzymes should include a thorough history, physical examination, and targeted laboratory testing, starting with a comprehensive metabolic panel and ultrasound of the liver, as recommended by the most recent study 1. The comprehensive metabolic panel should confirm the elevation and assess liver function, including ALT, AST, alkaline phosphatase, GGT, bilirubin, albumin, and prothrombin time. Key aspects of the history and physical examination include:
- Obesity
- Type 2 diabetes
- Metabolic syndrome
- Alcohol intake
- Medication history
- Family history of liver disease The laboratory testing should also include:
- Viral hepatitis serologies (hepatitis A, B, and C)
- Autoimmune causes with ANA, anti-smooth muscle antibody, and immunoglobulin levels
- Metabolic liver disease with iron studies, ceruloplasmin, and alpha-1 antitrypsin levels
- Lipid panel, hemoglobin A1c, and thyroid function tests to evaluate metabolic factors
- Carbohydrate-deficient transferrin to assess alcohol use The ultrasound of the liver can help assess for structural abnormalities, fatty infiltration, or biliary obstruction, and is a useful first-line investigation tool for mild increase in liver enzymes, as noted in 1. If initial testing is inconclusive and enzymes remain elevated for over 6 months, referral to a hepatologist for possible liver biopsy may be warranted, as suggested in 1 and 1. It's also important to consider the patient's overall clinical presentation and medical history when interpreting the results of the initial workup, and to tailor the diagnostic approach to the individual patient's needs, as emphasized in 1, 1, and 1.
From the Research
Initial Workup for Mildly Elevated Liver Enzymes
The initial workup for a patient with mildly elevated liver enzymes should include:
- A thorough medical history and physical examination to identify potential causes of liver enzyme elevation 2, 3
- Laboratory tests, such as:
- Complete blood count with platelets
- Serum albumin, iron, total iron-binding capacity, and ferritin levels
- Hepatitis C antibody and hepatitis B surface antigen testing
- Assessment for metabolic syndrome and insulin resistance (e.g., waist circumference, blood pressure, fasting lipid level, and fasting glucose or A1C level) 3
- Imaging studies, such as ultrasonography, to evaluate the liver and biliary tract 4, 3
Potential Causes of Mildly Elevated Liver Enzymes
Potential causes of mildly elevated liver enzymes include:
- Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) 3
- Drug-induced liver injury
- Hepatitis B and C
- Hereditary hemochromatosis
- Alpha1-antitrypsin deficiency
- Autoimmune hepatitis
- Wilson disease
- Extrahepatic sources, such as thyroid disorders, celiac sprue, hemolysis, and muscle disorders 3
- Choledocholithiasis, which can cause elevated liver enzymes in the absence of hepatocellular disease 5
Evaluation of Elevated Liver Enzymes
The evaluation of elevated liver enzymes should be based on the prevalence of diseases that cause asymptomatic transaminase elevations 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. If the elevation persists, further testing for uncommon causes should be considered 3.