From the Guidelines
A follow-up workup for elevated liver enzymes should begin with a detailed history, inventory of medications, and physical examination to assess for risk factors and signs of hepatic disease, as recommended by the American Gastroenterological Association 1. The evaluation should include a comprehensive approach to identify the underlying cause of the elevated liver enzymes.
- Repeat testing in 2-4 weeks to confirm persistence of abnormalities is essential.
- A comprehensive metabolic panel, complete blood count, and additional liver function tests including ALT, AST, alkaline phosphatase, bilirubin, albumin, and prothrombin time should be ordered.
- Specific testing should be based on suspected causes, such as hepatitis serologies (A, B, C), iron studies, ceruloplasmin for Wilson's disease, antimitochondrial antibodies for primary biliary cholangitis, and antinuclear antibodies for autoimmune hepatitis, as these conditions require prompt diagnosis and treatment to improve outcomes 1.
- Imaging studies such as ultrasound, CT, or MRI of the liver should be performed to assess for structural abnormalities, fatty liver, or masses.
- Lifestyle modifications are crucial during this period, including alcohol cessation, review of all medications (including over-the-counter drugs and supplements) for potential hepatotoxicity, and weight management if appropriate.
- For persistently elevated enzymes without clear cause after initial workup, referral to a gastroenterologist or hepatologist is recommended for consideration of liver biopsy, as persistent elevations of transaminases are predictive of relapse, activity on liver biopsy, progression to cirrhosis, and poor outcome 1. The timing and extent of follow-up depend on the degree of elevation, with AST/ALT greater than 3 times normal requiring more urgent evaluation, while mild elevations may allow for a more measured approach focusing first on modifiable factors.
From the Research
Follow-up Workup for Elevated Liver Enzymes
Elevated liver enzymes are a common problem faced by physicians, and the approach to evaluation and management can vary depending on the clinical presentation and pattern of injury 2, 3.
- The liver is a complex organ with multiple roles, and biochemical markers of hepatic function can be organized into groupings of hepatocellular, cholestatic, or functioning liver, based on underlying enzymatic roles 2.
- An algorithmic approach can be taken to help narrow the spectrum of a differential diagnosis, by separating disease processes into these groupings, followed by assessment of the magnitude of enzymatic elevation 2.
- The evaluation should be guided by both the clinical presentation and the pattern of injury, and should include a discussion of the various biochemical tests, their underlying biological basis, and an algorithmic approach to the interpretation of abnormalities 2, 3.
Diagnostic Approach
The diagnostic approach to elevated liver enzymes can vary depending on the clinical context, and may include:
- Non-invasive investigation, such as laboratory tests and imaging studies, to establish a cause for enzyme elevation 4.
- Liver biopsy, which can be reserved for patients with atypical treatment response or unclear diagnosis 4.
- A focused testing strategy, which can be more cost-effective than extensive testing, especially when accounting for pre-test probabilities and prior evaluations performed 5.
Common Causes of Elevated Liver Enzymes
Common causes of elevated liver enzymes include:
- Disease progression 4.
- Other drugs or toxins 4.
- Other causes, such as viral hepatitis, alcoholic and non-alcoholic fatty liver disease 3, 5.
- Immunotoxicity, which can be associated with higher peak ALT and ALT:AST ratio, and is more often seen in patients with prior CPI exposure, anti-CTLA-4-containing ICI treatments, and other organ immunotoxicities 4.