From the Guidelines
The workup for elevated liver enzymes, specifically for patients with hypertransaminasemia, should begin with a thorough history and physical examination, followed by appropriate laboratory and imaging studies, as outlined in the American Gastroenterological Association medical position statement 1. The initial evaluation should include a detailed history, inventory of medications, and a physical examination to assess the patient's risk factors for liver disease, medications, alcohol consumption, comorbid conditions, and signs and symptoms of hepatic disease.
- Basic initial testing should include:
- Repeat liver function tests to confirm the elevation and determine if it's persistent
- Complete blood count
- Comprehensive metabolic panel
- Coagulation studies (PT/INR)
- Hepatitis serologies (A, B, and C)
- Additional blood tests to consider include:
- Autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody)
- Iron studies
- Ceruloplasmin (for Wilson's disease)
- Alpha-1 antitrypsin levels
- Lipid profile Abdominal ultrasound is the recommended first-line imaging study to evaluate liver structure and rule out biliary obstruction, as suggested by the guidelines 1.
- If the etiology remains unclear, further imaging such as CT or MRI may be warranted.
- For patients with risk factors or persistent unexplained elevations, a liver biopsy might be necessary for definitive diagnosis, particularly in cases of chronic ALT or AST elevations (6 or more months) 1. Throughout this process, it's essential to address modifiable factors like alcohol consumption, medication review (including over-the-counter drugs and supplements), and metabolic risk factors.
- The pattern of enzyme elevation can provide diagnostic clues - predominantly elevated AST and ALT suggest hepatocellular injury, while elevated alkaline phosphatase and GGT point toward cholestatic or biliary disease 1. This systematic approach helps identify the underlying cause, which is crucial for appropriate management of liver disease.
From the Research
Evaluation of Elevated Liver Enzymes
The evaluation of elevated liver enzymes, specifically for patients with hypertransaminasemia (elevated alanine transaminase (ALT) and aspartate transaminase (AST)), involves a step-wise approach to determine the underlying cause of the enzyme elevation.
- The first step is to classify the enzyme alterations into patterns, including hepatocellular, cholestatic, and isolated hyperbilirubinemia 2, 3.
- For patients with a predominant increase in transaminase activities, the underlying cause may be a disturbance of hepatocellular integrity, which can be found in patients with viral hepatitis, genetic liver diseases, or drug-induced liver diseases 3.
- In patients with high serum alkaline phosphatase and γ-glutamyltranspeptidase activities, the underlying cause may be cholestatic liver diseases, and an ultrasound study can help discern intra- from extrahepatic cholestasis 3.
Diagnostic Approach
The diagnostic approach for elevated liver enzymes involves initial investigations, including:
- Laboratory tests to evaluate liver function and rule out other causes of enzyme elevation 2, 4.
- Imaging studies, such as ultrasound, to evaluate the liver and bile ducts 3.
- Liver biopsy may be reserved for patients with atypical treatment response or unclear diagnosis 5, 6.
Specific Causes of Elevated Liver Enzymes
Specific causes of elevated liver enzymes include:
- Viral hepatitis, genetic liver diseases, and drug-induced liver diseases, which can cause hepatocellular injury 3.
- Cholestatic liver diseases, such as primary and secondary sclerosing cholangitis, genetic disturbances of canalicular membrane transporters, or drug-induced liver diseases 3.
- Autoimmune hepatitis, which can occur in patients with human immunodeficiency virus (HIV) infection, particularly after immune status restoration 6.
- Immune checkpoint inhibitor immunotherapy, which can cause liver enzyme elevation due to immunotoxicity 5.