From the Guidelines
The initial workup for elevated transaminases should begin with a thorough history and physical examination, followed by targeted laboratory testing to determine the underlying cause, as recommended by the most recent guidelines 1. The initial evaluation should include a complete medical history, including medication use, alcohol consumption, herbal supplements, family history of liver disease, and risk factors for viral hepatitis. Laboratory testing should include a comprehensive metabolic panel, complete blood count, coagulation studies (PT/INR), and specific liver tests including alkaline phosphatase, bilirubin (total and direct), albumin, and gamma-glutamyl transferase. Additional first-line testing should include hepatitis serologies (hepatitis A, B, and C), autoimmune markers (ANA, anti-smooth muscle antibody, immunoglobulins), iron studies, ceruloplasmin (for Wilson's disease in younger patients), and alpha-1 antitrypsin levels. Imaging with an abdominal ultrasound should be performed to assess liver structure, rule out biliary obstruction, and evaluate for fatty infiltration or masses, as suggested by the American College of Radiology 1. Management depends on the identified cause but generally includes discontinuation of hepatotoxic medications or alcohol, treatment of underlying infections, weight loss for non-alcoholic fatty liver disease, and specific therapies for autoimmune or genetic conditions. For mild, asymptomatic elevations without a clear cause, monitoring transaminases every 2-4 weeks may be appropriate while avoiding hepatotoxins, as recommended by the Mayo Clinic Proceedings 1. Patients with severe elevations (>1000 IU/L), signs of liver failure (coagulopathy, encephalopathy), or concerning clinical features should be referred urgently to a hepatologist for specialized care and possible liver biopsy. Key considerations in the management of elevated transaminases include:
- Discontinuation of hepatotoxic medications or alcohol
- Treatment of underlying infections
- Weight loss for non-alcoholic fatty liver disease
- Specific therapies for autoimmune or genetic conditions
- Monitoring of transaminases and liver function tests
- Referral to a hepatologist for severe or concerning cases. The American Heart Association also recommends that statins are not contraindicated in patients with increased ASCVD risk with chronic, stable liver disease (e.g., nonalcoholic fatty liver), and limited data suggest potential benefit 1. Overall, the initial workup and management of elevated transaminases should be guided by a thorough history, physical examination, and targeted laboratory testing, with consideration of the underlying cause and potential therapies.
From the Research
Initial Workup for Transaminasemia
The initial workup for a patient presenting with elevated transaminases (transaminasemia) should include:
- Assessment for metabolic syndrome and insulin resistance (i.e., waist circumference, blood pressure, fasting lipid level, and fasting glucose or A1C level) 2
- Complete blood count with platelets
- Measurement of serum albumin, iron, total iron-binding capacity, and ferritin 2, 3, 4
- Hepatitis C antibody and hepatitis B surface antigen testing 2, 5, 3, 4
Evaluation of Common Causes
The most common causes of elevated transaminase levels are:
- Nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) 2, 5, 3
- Alcoholic liver disease 2, 5, 3, 6
- Uncommon causes include drug-induced liver injury, hepatitis B and C, and hereditary hemochromatosis 2, 5, 3
- Rare causes include alpha1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease 2, 5, 3
Further Testing and Management
If testing for common causes is consistent with NAFLD or MASLD and is otherwise unremarkable, a trial of lifestyle modification is appropriate 2, 3