From the Guidelines
Transaminitis workup should begin with monitoring patient for abnormal liver blood tests, including AST, ALT, and bilirubin, and reviewing medications and supplements that may cause hepatotoxicity, as recommended by the ASCO guideline update 1. When evaluating transaminitis, the following steps should be taken:
- Monitor liver function tests (LFTs) before each infusion and/or consider weekly monitoring if grade 1 LFT elevations are present, with no treatment recommended for grade 1 LFT abnormality 1.
- Review medications and supplements that may cause hepatotoxicity and rule out abnormal liver enzymes from development or progression of liver metastases 1.
- Consider liver biopsy if the patient is steroid-refractory or if there is concern for other differential diagnoses that would alter medical management 1.
- For grade 2 or higher elevations, workup for other causes of elevated liver enzymes, such as viral hepatitis, alcohol history, iron studies, thromboembolic event, or potential liver metastasis from primary malignancy, should be performed using blood work and imaging (ultrasound and cross-sectional imaging) 1. Key laboratory tests to consider include:
- Complete metabolic panel
- Complete blood count
- Coagulation studies (PT/INR)
- Additional liver function tests, including alkaline phosphatase, bilirubin, albumin, and gamma-glutamyl transferase
- Viral hepatitis serologies (hepatitis A, B, C, E)
- Tests for autoimmune causes, such as antinuclear antibody, anti-smooth muscle antibody, and immunoglobulin levels
- Iron studies, ceruloplasmin, alpha-1 antitrypsin levels, and lipid profile to evaluate metabolic and genetic causes Abdominal ultrasound is recommended as the first-line imaging to assess liver structure and rule out biliary obstruction 1. In cases of persistent unexplained transaminitis, consider liver biopsy, and management depends on the underlying cause, ranging from lifestyle modifications for non-alcoholic fatty liver disease (NAFLD) to specific treatments for viral, autoimmune, or metabolic conditions 1.
From the Research
Transaminitis Workup
- The workup for transaminitis involves assessing abnormal liver chemistries, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin 2
- Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels, while cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 2
- The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 2
Causes of Transaminitis
- Transaminitis can be caused by various factors, including statin use 3, antituberculous therapy 4, and valoctocogene roxaparvovec gene therapy 5
- In patients with anorexia nervosa, transaminitis can be caused by severe malnutrition, and early weight restoration is essential to improve liver chemistry 6
- Drug interactions can also contribute to transaminitis, as seen in cases of statin-related transaminitis 3
Management of Transaminitis
- The management of transaminitis depends on the underlying cause and may involve discontinuation of the offending medication, such as statins 3 or antituberculous therapy 4
- Corticosteroids may be used to mitigate transaminitis-associated decline in FVIII levels following valoctocogene roxaparvovec gene therapy 5
- In cases of severe transaminitis, liver biopsy may be necessary to determine the underlying cause and guide management 2, 6