From the Research
The most accurate serum test to determine the cause of elevated liver transaminases is a comprehensive hepatic panel combined with targeted serologic testing based on clinical suspicion, as recommended by the most recent study 1. This approach should begin with a complete metabolic panel including ALT, AST, alkaline phosphatase, bilirubin, albumin, and prothrombin time to assess liver function comprehensively. Additional first-line tests should include:
- Hepatitis viral serologies (HBsAg, anti-HCV)
- Autoimmune markers (ANA, anti-smooth muscle antibody, immunoglobulins)
- Iron studies (ferritin, transferrin saturation)
- Ceruloplasmin for Wilson's disease
- Alpha-1 antitrypsin levels Imaging studies like ultrasound should complement these tests to evaluate for structural abnormalities. For suspected alcoholic liver disease, AST:ALT ratio >2 is suggestive, while GGT can help confirm alcohol-related injury. For suspected non-alcoholic fatty liver disease, ultrasound findings combined with metabolic risk factors and exclusion of other causes is diagnostic. The accuracy of diagnosis improves significantly when these tests are interpreted together with the patient's clinical history, risk factors, and physical examination findings, as no single test can definitively determine the cause of elevated transaminases in all cases, as also supported by 2 and 3.
Some key points to consider in the evaluation of elevated transaminases include:
- The most common causes of mildly elevated transaminase levels are metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease, as noted in 1
- Uncommon causes include drug-induced liver injury, chronic hepatitis B and C, and hereditary hemochromatosis
- Rare causes are alpha1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease
- Extrahepatic causes are celiac disease, hyperthyroidism, rhabdomyolysis, and pregnancy-associated liver disease, as mentioned in 1 and 2
- 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, as recommended in 1 and 2.
It is essential to prioritize the most recent and highest quality study, which in this case is 1, to ensure that the recommended approach is based on the latest evidence and guidelines.