From the Guidelines
The diagnostic workup for transaminitis should begin with a thorough history and physical examination, focusing on risk factors for liver disease, and initial laboratory testing should include a comprehensive metabolic panel, complete blood count, coagulation studies, and additional liver function tests, as recommended by the most recent guidelines 1. The initial evaluation of abnormal liver tests includes a detailed history, inventory of medications, and a physical examination, which should include an assessment of the patient’s risk factors for liver disease, medications, alcohol consumption, comorbid conditions, and signs and symptoms of hepatic disease 1. Key aspects of the diagnostic workup include:
- Initial laboratory testing: comprehensive metabolic panel, complete blood count, coagulation studies (PT/INR), and additional liver function tests including alkaline phosphatase, bilirubin, albumin, and gamma-glutamyl transferase
- Specific etiologic testing: viral hepatitis serologies (hepatitis A, B, C, E), autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody, immunoglobulin levels), iron studies (ferritin, transferrin saturation), ceruloplasmin for Wilson's disease, and alpha-1 antitrypsin levels
- Imaging studies: abdominal ultrasound to assess liver structure, biliary system, and evaluate for fatty infiltration or masses, with further imaging such as CT or MRI as indicated
- For persistent unexplained transaminitis, a liver biopsy may be necessary for definitive diagnosis, as suggested by recent guidelines 1 Throughout the workup, it's essential to address modifiable factors like discontinuing hepatotoxic medications or alcohol, and to consider the patient's clinical context and risk factors for liver disease, as emphasized in the guidelines 1.
From the Research
Diagnostic Workup of Transaminitis
The diagnostic workup of transaminitis involves a stepwise evaluation based on the prevalence of diseases that cause mild elevations in transaminase levels 2, 3. The most common causes of elevated transaminase levels are:
- Nonalcoholic fatty liver disease
- Alcoholic liver disease
- Medication-associated liver injury
- Viral hepatitis (hepatitis B and C)
- Hemochromatosis
Initial Testing
Initial testing should include:
- Fasting lipid profile
- Measurement of glucose, serum iron, and ferritin
- Total iron-binding capacity
- Hepatitis B surface antigen and hepatitis C virus antibody testing 2, 3
- Assessment for metabolic syndrome and insulin resistance (i.e., waist circumference, blood pressure, fasting lipid level, and fasting glucose or A1C level) 3
Further Testing
If test results are normal, a trial of lifestyle modification with observation or further testing for less common causes is appropriate 2, 3. Additional testing may include:
- Ultrasonography
- Measurement of α(1)-antitrypsin and ceruloplasmin
- Serum protein electrophoresis
- Antinuclear antibody, smooth muscle antibody, and liver/kidney microsomal antibody type 1 testing 2
- Hepatic ultrasonography and further testing for uncommon causes should be considered if the elevation persists 3
Referral for Further Evaluation
Referral for further evaluation and possible liver biopsy is recommended if transaminase levels remain elevated for six months or more 2. A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 4.