From the Guidelines
Mild elevated liver enzymes (transaminitis) should be evaluated with a thorough workup, including a comprehensive history and physical examination, laboratory testing, and imaging studies, to identify the underlying cause and prevent potential liver disease progression. The workup for mild transaminitis should begin with a review of medications and supplements that may cause hepatotoxicity, as well as ruling out abnormal liver enzymes from development or progression of liver metastases 1. Initial laboratory testing should include a complete metabolic panel, complete blood count, and coagulation studies, as well as specific liver tests such as hepatitis serologies (A, B, and C), iron studies, and autoimmune markers such as ANA, anti-smooth muscle antibody, and anti-mitochondrial antibody. According to the most recent study 1, liver function tests are often obtained as part of standard laboratory panels in asymptomatic and symptomatic patients, and alteration in the biochemical markers of hepatocyte damage or bile flow indicate hepatobiliary insult rather than a measurement of liver function. The severity of abnormal aminotransferase can be classified as mild: <5 times the upper reference limit, and ultrasound of the liver is recommended to assess for structural abnormalities, fatty infiltration, or biliary obstruction. If the patient is overweight or has metabolic risk factors, non-alcoholic fatty liver disease should be considered, and management involves addressing the underlying cause, such as discontinuing hepatotoxic medications, reducing alcohol intake, or treating viral hepatitis. For mild transaminitis without a clear cause, lifestyle modifications including weight loss, regular exercise, and avoiding alcohol are recommended, and follow-up liver function tests should be performed in 4-6 weeks to monitor progression 1. Persistent or worsening transaminitis may require referral to a hepatologist and consideration of liver biopsy, as mild transaminitis can be the first indication of significant liver disease that may progress if left untreated. Key points to consider in the workup of mild transaminitis include:
- Comprehensive history and physical examination
- Laboratory testing, including complete metabolic panel, complete blood count, and coagulation studies
- Specific liver tests, such as hepatitis serologies and autoimmune markers
- Imaging studies, such as ultrasound of the liver
- Lifestyle modifications, including weight loss, regular exercise, and avoiding alcohol
- Follow-up liver function tests to monitor progression.
From the Research
Initial Evaluation
The initial evaluation for mild elevated liver enzymes (transaminitis) should include:
- A 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
- Assessment for metabolic syndrome and insulin resistance (i.e., waist circumference, blood pressure, fasting lipid level, and fasting glucose or A1C level) 3
- A complete blood count with platelets
- Measurement of serum albumin, iron, total iron-binding capacity, and ferritin 3
Common Causes
The most common causes of elevated transaminase levels are:
- Nonalcoholic fatty liver disease 2, 3
- Alcoholic liver disease 2, 3
- Medication-associated liver injury 2, 4
- Viral hepatitis (hepatitis B and C) 2, 5, 3, 6
- Hemochromatosis 2, 3, 4
Less Common Causes
Less common causes of elevated transaminase levels include:
- α(1)-antitrypsin deficiency 2, 3, 6, 4
- Autoimmune hepatitis 2, 3, 6, 4
- Wilson disease 2, 3, 4
- Extrahepatic conditions (e.g., thyroid disorders, celiac disease, hemolysis, muscle disorders) 2, 3, 4
Further Testing
If the initial evaluation does not reveal a cause, further testing may include:
- Ultrasonography 2, 3, 4
- Measurement of α(1)-antitrypsin and ceruloplasmin 2
- Serum protein electrophoresis 2
- Antinuclear antibody, smooth muscle antibody, and liver/kidney microsomal antibody type 1 testing 2
- Referral for further evaluation and possible liver biopsy if transaminase levels remain elevated for six months or more 2, 4