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 most recent guidelines 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 1.
Key Components of the Workup
- Repeat liver function tests to confirm the elevation and determine the pattern (hepatocellular vs cholestatic)
- Order a comprehensive metabolic panel, complete blood count, and coagulation studies
- Specific tests should include:
- Hepatitis serologies (A, B, C)
- Autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody)
- Iron studies (ferritin, transferrin saturation)
- Ceruloplasmin for Wilson's disease
- Alpha-1 antitrypsin levels
- Lipid profile
Imaging Studies
- Ultrasound of the liver is the initial imaging study of choice to assess for structural abnormalities, fatty infiltration, or biliary obstruction 1
- Additional testing may include CT or MRI depending on initial findings
Additional Considerations
- Consider medication review as many drugs can cause liver enzyme elevation, including acetaminophen, statins, antibiotics, and herbal supplements
- Alcohol use should be assessed and quantified
- For persistent unexplained elevations, referral to a gastroenterologist or hepatologist is appropriate, who may recommend liver biopsy for definitive diagnosis 1 The systematic approach is important because liver enzyme elevations can indicate various conditions ranging from benign to serious liver diseases, and proper identification of the underlying cause guides appropriate treatment 1.
From the Research
Evaluation of Elevated Liver Enzymes
Elevated liver enzymes, specifically hypertransaminasemia (elevated alanine transaminase (ALT) and aspartate transaminase (AST)), require a systematic approach to determine the underlying cause. The evaluation should be guided by the clinical presentation and the pattern of injury 2, 3.
Patterns of Liver Enzyme Elevation
There are three main patterns of liver enzyme elevation:
- Hepatocellular pattern: characterized by a predominant increase in transaminase activities, indicating a disturbance of hepatocellular integrity, which can be found in patients with viral hepatitis, genetic liver diseases, and drug-induced liver diseases 3.
- Cholestatic pattern: 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, or drug-induced liver diseases 3.
- Isolated hyperbilirubinemia: characterized by a predominant rise in bilirubin levels, which can be observed in patients with hemolytic anemias, Gilbert's syndrome, or other conditions affecting bilirubin metabolism 2.
Diagnostic Approach
The diagnostic approach to elevated liver enzymes should include:
- Initial investigations, such as liver function tests, complete blood count, and coagulation studies 2.
- Imaging studies, such as ultrasound, to discern intra- from extrahepatic cholestasis 3.
- Liver biopsy, which can be reserved for patients with atypical treatment response or unclear diagnosis 4.
- A biochemical signature with higher ALT and ALT/AST ratio, a history of prior immune checkpoint inhibitor exposure, and other organ immunotoxicities may help to identify patients at a higher likelihood of immunotoxicity 4.
Management
The management of elevated liver enzymes should be guided by the underlying cause and clinical presentation. In some cases, liver enzyme elevation may be self-limiting, and values may normalize spontaneously during follow-up 3. In other cases, specific treatment may be required to address the underlying condition. An algorithmic approach can be taken to help narrow the spectrum of a differential diagnosis and ensure appropriate management and evaluation of the patient with elevated liver enzymes 5.