From the Guidelines
The workup for elevated liver function tests (LFTs) should begin with a thorough history and physical examination, focusing on risk factors such as alcohol use, medications, supplements, family history, and symptoms, as recommended by the most recent study 1.
Initial Evaluation
The initial evaluation should include a comprehensive metabolic panel, complete blood count, coagulation studies, and repeat LFTs to confirm abnormalities.
- Additional first-line tests include:
- Hepatitis serologies (A, B, and C)
- Iron studies
- Ceruloplasmin (for Wilson's disease)
- Antimitochondrial antibodies (for primary biliary cholangitis)
- Anti-smooth muscle antibodies (for autoimmune hepatitis)
- Immunoglobulin levels
Imaging Studies
Imaging with an ultrasound of the liver should be performed to assess for structural abnormalities, fatty infiltration, or biliary obstruction, as suggested by 1.
Specialized Testing
If these initial tests are inconclusive, consider specialized testing such as:
- Alpha-1 antitrypsin levels
- Celiac disease antibodies
- Testing for less common conditions like hemochromatosis
Referral to a Specialist
For persistent unexplained elevations, referral to a hepatologist is appropriate, who may recommend a liver biopsy for definitive diagnosis, as recommended by 1 and 1.
Pattern of LFT Elevation
The pattern of LFT elevation (hepatocellular vs cholestatic) helps guide the diagnostic approach, with AST/ALT elevations suggesting hepatocellular injury and alkaline phosphatase/GGT elevations indicating cholestatic or infiltrative processes, as noted in 1 and 1.
Monitoring Schedule
Liver tests should be performed at least weekly for the first 2 cycles of treatment in Phase 1 studies, or for the first 6–8 weeks, and then every 2–4 weeks, depending on the preclinical findings, the patient population and combination treatments, as recommended by 1.
From the Research
Evaluation of Elevated LFTs
- The evaluation of patients with elevated liver function tests (LFTs) requires a comprehensive approach, including a discussion of the various biochemical tests and their underlying biological basis 2.
- An algorithmic approach can be taken to help narrow the spectrum of a differential diagnosis, by separating disease processes into groupings of hepatocellular, cholestatic, or functioning liver, based on underlying enzymatic roles 2.
- The prescribing of medicines to patients with abnormal LFTs requires careful consideration, including the use of potentially hepatotoxic drugs and the need for dose modification in patients with cirrhosis 3.
Management of Elevated LFTs
- In patients with elevated LFTs, it is essential to establish the cause of the abnormal liver function and determine whether the patient has cirrhosis, as this will have broad-reaching implications for prescribing 3.
- The development of LFT abnormalities while on certain therapies, such as posaconazole, may not warrant a switch to an alternative therapy, as hepatotoxicity is often multifactorial and generally resolves with time in the majority of patients 4.
- Autoantibody positivity, including antinuclear antibodies (ANA), may be detected in patients with chronic hepatitis B and C, and can be associated with disease profile and response to treatment 5, 6.
Laboratory Tests
- Laboratory tests, including LFTs and autoantibody tests, are essential in the evaluation and management of patients with elevated LFTs 2, 5, 6.
- The results of these tests can help guide the diagnosis and treatment of patients with liver disease, and can also help identify potential hepatotoxicity associated with certain therapies 3, 4.