From the Guidelines
When a patient has elevated liver enzymes, start with a thorough history and physical examination to identify potential causes, as this approach is supported by the most recent guidelines 1. This initial step is crucial in determining the underlying cause of the elevated liver enzymes. Ask about alcohol use, medications (including over-the-counter drugs and supplements), recent illnesses, and family history of liver disease.
- Order a comprehensive metabolic panel to assess liver function tests including ALT, AST, alkaline phosphatase, GGT, bilirubin, and albumin.
- Calculate the AST/ALT ratio, as a ratio >2 often suggests alcoholic liver disease while a ratio <1 may indicate viral hepatitis or fatty liver 1.
- Test for viral hepatitis with hepatitis A, B, and C serologies.
- Consider autoimmune markers such as ANA, anti-smooth muscle antibody, and anti-mitochondrial antibody.
- Evaluate for metabolic causes with iron studies, ceruloplasmin (for Wilson's disease), and alpha-1 antitrypsin levels.
- Ultrasound of the liver is recommended as the initial imaging study to assess for structural abnormalities, fatty infiltration, or biliary obstruction 1. The pattern of enzyme elevation often provides diagnostic clues - hepatocellular patterns (predominantly elevated ALT/AST) suggest viral hepatitis or drug-induced injury, while cholestatic patterns (predominantly elevated alkaline phosphatase/GGT) suggest biliary obstruction or certain medications.
- For persistent unexplained elevations, consider referral to a gastroenterologist or hepatologist for possible liver biopsy. It is essential to note that the interpretation of abnormal liver chemistries must be taken in the clinical context of a given patient 1.
From the Research
Initial Evaluation
When a patient presents with elevated liver enzymes, the initial evaluation should involve a step-wise algorithm that classifies enzyme alterations based on pattern (hepatocellular, cholestatic, and isolated hyperbilirubinemia) 2. This approach helps to identify the most common causes of enzyme alteration and suggests initial investigations.
Classification of Enzyme Alterations
Abnormal liver biochemical tests can be categorized based on the pattern and magnitude of aminotransferase elevation 3. The patterns include:
- Hepatocellular pattern
- Cholestatic pattern
- Isolated hyperbilirubinemia
Hepatocellular Pattern
The hepatocellular pattern causes include:
- Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis
- Alcohol use
- Chronic viral hepatitis
- Liver cirrhosis (variable)
- Autoimmune hepatitis
- Hemochromatosis
- Wilson's disease
- Alpha-1 antitrypsin deficiency
- Celiac disease
- Medication-induced
- Ischemic hepatitis 3
Cholestatic Pattern
The cholestatic pattern causes include:
- Biliary pathology (obstruction, autoimmune)
- Other conditions with hyperbilirubinemia (conjugated and unconjugated) 3
Diagnostic Work-up
The diagnostic work-up for elevated liver enzymes should be guided by both the clinical presentation and the pattern of injury 4. Initial investigations may include:
- Liver biochemical tests (aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, albumin, prothrombin time, and international normalized ratio)
- Imaging studies (ultrasound, CT, or MRI)
- Serological tests (hepatitis panel, autoimmune markers)
Coagulation Testing
In patients with liver disease, coagulation testing can be challenging due to the complexity of the hemostasis system 5, 6. Global tests of clot formation, such as viscoelastic testing and thrombin generation analysis, may provide practical information to guide decision-making. However, optimal target levels have not been validated 6.