From the Guidelines
The workup and management of elevated liver enzymes should begin with a thorough history and physical examination, followed by appropriate laboratory testing to determine the underlying cause, as recommended by the most recent guidelines 1. The initial evaluation should include a complete metabolic panel, complete blood count, coagulation studies, and additional liver tests including alkaline phosphatase, bilirubin, albumin, and gamma-glutamyl transferase.
- Depending on the pattern of elevation (hepatocellular vs cholestatic), specific testing should be pursued.
- For hepatocellular patterns, test for viral hepatitis (hepatitis A, B, C), autoimmune hepatitis (ANA, anti-smooth muscle antibody), hemochromatosis (iron studies), and Wilson's disease (ceruloplasmin) in younger patients.
- For cholestatic patterns, consider ultrasound to evaluate for biliary obstruction, and test for primary biliary cholangitis and primary sclerosing cholangitis. Management involves treating the underlying cause:
- discontinuing hepatotoxic medications,
- lifestyle modifications for non-alcoholic fatty liver disease (weight loss, diabetes control),
- abstinence for alcoholic liver disease,
- antiviral therapy for viral hepatitis,
- immunosuppression for autoimmune conditions,
- and endoscopic or surgical intervention for biliary obstruction. Serial monitoring of liver enzymes is essential to assess response to treatment. The urgency of workup depends on the degree of elevation, with AST/ALT >1000 U/L or evidence of liver failure (elevated INR, encephalopathy) requiring immediate hospitalization and specialist consultation, as supported by recent studies 1. In cases of immune-related adverse events, such as those associated with immune checkpoint inhibitors, specific guidelines should be followed, including the management of grade 1-4 liver toxicity, as outlined in recent recommendations 1.
From the Research
Evaluation of Elevated Liver Enzymes
Elevated liver enzymes can be caused by various underlying conditions, and a thorough workup is necessary to determine the cause. The following steps can be taken:
- Obtain a thorough history and physical examination to identify potential causes of elevated liver enzymes 2
- Order appropriate blood tests, including liver function tests (LFTs) and other tests to evaluate for infectious, autoimmune, genetic, metabolic, drug, and vascular causes 2
- Use an algorithmic approach to interpret LFT abnormalities, separating disease processes into hepatocellular, cholestatic, or functioning liver groupings 3
- Consider the magnitude of enzymatic elevation to narrow the differential diagnosis 3
Testing Strategies
Two testing strategies can be employed: extensive testing or focused testing. Extensive testing involves testing for all possible diseases at once, while focused testing involves testing for common diseases first 4. The choice of testing strategy depends on the patient's history and physical exam, as well as the pre-test probabilities of various diseases.
- Extensive testing may be more cost-effective when there are no clues available at the time of evaluation, but it can generate more false positives 4
- Focused testing is more cost-effective when there are strong clues regarding the likelihood of a particular disease, and it can save time, money, and prevent false positives 4
Management
The management of elevated liver enzymes depends on the underlying cause. For example:
- Autoimmune hepatitis can be treated with immunosuppressive agents and ursodeoxycholic acid 5, 6
- Hepatitis E virus infection can be treated with supportive care, and in some cases, treatment for autoimmune hepatitis may be necessary 6
- Other causes of elevated liver enzymes, such as drug-induced liver injury or vascular causes, require specific treatment based on the underlying condition 2
Key Considerations
- A thorough history and physical examination are essential in evaluating patients with elevated liver enzymes 2
- An understanding of the patterns of aminotransferase and alkaline phosphatase elevations is useful in narrowing the differential diagnosis 2
- Imaging and other diagnostic tests may be necessary to evaluate the patient with abnormal liver enzymes 2