From the Guidelines
Elevated liver enzymes, specifically Alanine Transaminase (ALT) and Aspartate Transaminase (AST), are primarily caused by hepatocellular injury, which can be due to various factors including fatty liver disease, viral hepatitis, medications, and autoimmune hepatitis, as evident from the most recent study published in 2024 1.
Causes of Elevated Liver Enzymes
The causes of elevated liver enzymes can be categorized into several groups, including:
- Hepatocellular injury, which can be caused by fatty liver disease, viral hepatitis, medications, and autoimmune hepatitis
- Cholestatic liver disease, which can be caused by biliary obstruction, primary biliary cirrhosis, and primary sclerosing cholangitis
- Genetic disorders, such as hemochromatosis and Wilson's disease
- Other factors, such as obesity, diabetes, heart failure, celiac disease, thyroid disorders, and muscle disorders
Diagnosis and Evaluation
The diagnosis and evaluation of elevated liver enzymes involve a thorough history and physical examination, laboratory tests, and imaging studies. The pattern of enzyme elevation can provide clues about the underlying cause, with hepatocellular damage typically raising ALT and AST more significantly, while biliary issues tend to elevate ALP and GGT 1.
Recommended Evaluation
The recommended evaluation for patients with treatment-emergent ALT elevation includes first-line testing, such as thorough history, serum creatine kinase, hepatitis A, B, and C testing, autoantibody and immunoglobulin testing, and hepatobiliary imaging 1.
Importance of Identifying the Underlying Cause
Identifying the underlying cause of elevated liver enzymes is crucial to provide appropriate treatment and prevent further liver damage. The treatment approach may include lifestyle modifications, medication adjustments, or specific therapies depending on the diagnosis, as highlighted in the study published in 2023 1.
Key Takeaways
- Elevated liver enzymes are primarily caused by hepatocellular injury
- The causes of elevated liver enzymes can be categorized into several groups, including hepatocellular injury, cholestatic liver disease, genetic disorders, and other factors
- The diagnosis and evaluation of elevated liver enzymes involve a thorough history and physical examination, laboratory tests, and imaging studies
- Identifying the underlying cause of elevated liver enzymes is crucial to provide appropriate treatment and prevent further liver damage.
From the Research
Causes of Elevated Liver Enzymes
Elevated liver enzymes, specifically elevated Alanine Transaminase (ALT) and Aspartate Transaminase (AST), can be caused by various factors. The main causes can be categorized into three patterns:
- A predominant increase in transaminase activities, which reflects a disturbance of hepatocellular integrity, can be found in patients with:
- A second pattern is characterized by high serum alkaline phosphatase and γ-glutamyltranspeptidase activities, indicating cholestatic liver diseases, such as:
- Primary and secondary sclerosing cholangitis
- Genetic disturbances of canalicular membrane transporters
- Drug-induced liver diseases
- Obstruction of the large bile ducts by gall stones or tumors 2
- A third pattern is defined by a predominant rise in γ-glutamyl transpeptidase, which is observed in:
- Alcoholic or non-alcoholic fatty liver disease
- Infiltrating liver diseases 2
Specific Causes of Elevated ALT and AST
Elevated serum levels of transaminases (AST and ALT) usually indicate hepatocellular damage, but can also be of extrahepatic origin, such as muscle damage 3. The most frequent diagnoses in asymptomatic patients with accidentally detected, mostly mild to moderate transaminase elevations are:
- Alcoholic liver disease
- Chronic viral hepatitis
- Drug-induced liver disease
- Non-alcoholic steatosis 3, 4 In cases of severe acute liver injury, the differential diagnosis of an increase in ALT and/or AST level of ≥1000 IU/L often includes:
- Ischemic hepatitis
- Acute viral hepatitis
- Drug-induced liver injury (DILI) 5 Chronic liver injury can also be induced by drugs and toxins, resulting in various forms of chronic DILI, including non-alcoholic fatty liver disease, vascular lesions, and cirrhosis 6.
Evaluation and Diagnosis
Initial laboratory testing for elevated transaminase levels 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 4. 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 4.