From the Guidelines
The evaluation of transaminitis should begin with a thorough history and physical examination, focusing on risk factors like alcohol use, medications, and family history of liver disease, as recommended by the most recent guidelines 1. The initial laboratory testing should include a comprehensive metabolic panel, complete blood count, and coagulation studies. Specific liver tests should measure ALT, AST, alkaline phosphatase, GGT, bilirubin, albumin, and prothrombin time.
- The pattern of enzyme elevation helps direct further workup:
- hepatocellular (predominantly elevated ALT/AST) suggests viral hepatitis, medication toxicity, or autoimmune hepatitis,
- while cholestatic (predominantly elevated alkaline phosphatase/GGT) suggests biliary obstruction or infiltrative diseases. For mild elevations (less than 5 times normal), consider non-alcoholic fatty liver disease, alcohol-related liver disease, and medication effects.
- For moderate to severe elevations, test for:
- viral hepatitis (hepatitis A, B, C)
- autoimmune markers (ANA, anti-smooth muscle antibody)
- iron studies
- ceruloplasmin (Wilson's disease)
- alpha-1 antitrypsin levels Imaging studies like ultrasound should be performed early to assess liver structure and rule out biliary obstruction.
- If the diagnosis remains unclear after initial evaluation, consider liver biopsy, as recommended by previous studies 1. Management involves treating the underlying cause, discontinuing hepatotoxic medications, lifestyle modifications, and monitoring liver enzymes until resolution, with the goal of improving morbidity, mortality, and quality of life.
- The approach to evaluating transaminitis should be individualized, taking into account the patient's specific clinical scenario and risk factors, as emphasized by the American Gastroenterological Association 1.
From the Research
Evaluation Approach
To evaluate transaminitis, which refers to elevated liver enzymes, several steps and considerations are involved:
- Initial assessment: This includes a thorough medical history and physical examination to identify potential causes of liver enzyme elevation, such as alcohol use, drug intake, or symptoms suggestive of liver disease 2, 3.
- Laboratory tests: Initial laboratory testing should assess complete blood cell count with platelets, blood glucose, lipid profile, hepatitis B surface antigen, hepatitis C antibody, serum albumin, iron, total iron-binding capacity, and ferritin 2, 3.
- Specific scores and indices: If metabolic dysfunction-associated steatotic liver disease (MASLD) is suspected, the FIB-4 Index Score or NAFLD Fibrosis Score can be used to predict which patients are at risk for fibrosis and may benefit from further testing or referral to a hepatologist 2.
- Imaging and further testing: Hepatic ultrasonography and further testing for uncommon causes should be considered if the elevation persists after initial evaluation and lifestyle modification trials 3.
- Discrimination between causes: In cases where discrimination between idiosyncratic drug-induced liver injury (DILI) and autoimmune hepatitis (AIH) is necessary, models like the Beijing-AID (BJ-AID) can be useful, utilizing parameters such as aspartate transaminase, globulin, prealbumin, creatinine, and platelet count 4.
Common Causes
The most common causes of mildly elevated transaminase levels include:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease 2, 3.
- Uncommon causes: drug-induced liver injury, chronic hepatitis B and C, and hereditary hemochromatosis 2, 3.
- Rare causes: alpha1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease 2, 3.
- Extrahepatic causes: celiac disease, hyperthyroidism, rhabdomyolysis, and pregnancy-associated liver disease 2, 3.
Management
All patients with elevated transaminases should be counseled about: