From the Guidelines
Elevated liver function tests (LFTs) without a history of documented liver disease require a systematic approach to identify the underlying cause, starting with a complete medical history and a comprehensive panel of liver tests, as recommended by the guidelines on the management of abnormal liver blood tests 1. To determine the cause of elevated LFTs, the following steps should be taken:
- Obtain a complete medical history focusing on alcohol use, medications, family history of liver disease, and risk factors for viral hepatitis.
- Order a comprehensive panel including ALT, AST, alkaline phosphatase, GGT, bilirubin, albumin, and prothrombin time to characterize the pattern of liver injury (hepatocellular vs. cholestatic).
- Additional testing should include hepatitis serologies (A, B, C), autoimmune markers (ANA, anti-smooth muscle antibody, immunoglobulins), iron studies, ceruloplasmin (for Wilson's disease), and alpha-1 antitrypsin levels.
- An ultrasound of the liver should be performed to assess for structural abnormalities, fatty infiltration, or biliary obstruction. Common causes of elevated LFTs include non-alcoholic fatty liver disease, alcoholic liver disease, medication-induced liver injury, viral hepatitis, and autoimmune hepatitis. Management depends on the identified cause but often includes lifestyle modifications such as weight loss, alcohol cessation, and discontinuation of hepatotoxic medications. Patients with significantly elevated LFTs (>3 times upper limit of normal) or signs of liver dysfunction should be referred to a hepatologist for further evaluation and management, as recommended by the guidelines on the management of abnormal liver blood tests 1. It is essential to note that the response to abnormal liver blood tests should be to obtain a thorough clinical history and determine the cause, unless there is a high index of clinical suspicion that it is a transient finding 1. In patients with more marked elevations in ALT (>1000 U/L), other possible causes of viral hepatitis should be considered, including hepatitis A and E and cytomegalovirus 1. The choice of blood tests in the core panel is influenced by prevalence and the identification of treatable causes of liver disease, as recommended by the guidelines on the management of abnormal liver blood tests 1.
From the Research
Evaluation of Elevated LFTs
Elevated liver function tests (LFTs) can be a common problem in patients with no history of documented liver disease. The following steps can be taken to evaluate and manage these patients:
- Determine the etiology of the underlying liver disease 2
- Evaluate the severity of the liver dysfunction and determine if acute liver failure (ALF) or acute decompensation of chronic liver failure is present 2
- Look for the presence of associated complications-either those of ALF or chronic liver failure as appropriate 2
- Use a stepwise evaluation based on the prevalence of diseases that cause mild elevations in transaminase levels 3
Common Causes of Elevated LFTs
The most common causes of mildly elevated liver transaminase levels include:
- Nonalcoholic fatty liver disease, which can affect up to 30 percent of the population 3
- Alcoholic liver disease 3
- Medication-associated liver injury 3
- Viral hepatitis (hepatitis B and C) 3
- Hemochromatosis 3
Diagnostic Evaluation
Initial testing should include:
- A fasting lipid profile 3
- Measurement of glucose, serum iron, and ferritin 3
- Total iron-binding capacity 3
- Hepatitis B surface antigen and hepatitis C virus antibody testing 3 Additional testing may include ultrasonography, measurement of α(1)-antitrypsin and ceruloplasmin, serum protein electrophoresis, and antinuclear antibody, smooth muscle antibody, and liver/kidney microsomal antibody type 1 testing 3
Management
A systematic, stepwise approach to the evaluation and management of abnormal liver test results is recommended to optimize high-value care 4. Referral for further evaluation and possible liver biopsy is recommended if transaminase levels remain elevated for six months or more 3.