What to order for elevated LFT?

From the Guidelines

Elevated LFTs should be investigated with imaging studies, specifically US abdomen, US duplex Doppler abdomen, and CT abdomen and pelvis with IV contrast, depending on the pattern of liver enzyme elevation.

Initial Evaluation

The initial evaluation of elevated LFTs involves determining the pattern of liver enzyme elevation, which can be hepatocellular, cholestatic, or mixed.

• Hepatocellular pattern: characterized by elevated aminotransferases (AST and ALT) with or without elevated bilirubin and alkaline phosphatase (ALP) 1.
• Cholestatic pattern: characterized by elevated ALP and gamma-glutamyl transpeptidase (GGT) with or without elevated bilirubin 1.

Imaging Studies

The choice of imaging study depends on the pattern of liver enzyme elevation and the clinical presentation.

• US abdomen and US duplex Doppler abdomen are usually appropriate as the initial imaging for patients with hepatocellular predominance and mild aminotransferase increase 1.
• US abdomen, US duplex Doppler abdomen, and CT abdomen and pelvis with IV contrast are usually appropriate as the initial imaging for patients with hepatocellular predominance and moderate or severe aminotransferase increase 1.
• US abdomen, MRI abdomen without and with IV contrast, and CT abdomen and pelvis with IV contrast are usually appropriate as the initial imaging of patients with cholestatic predominance and elevated ALP with or without elevated GGT 1.

Additional Evaluation

Additional evaluation may include calculation of a FIB4 or NAFLD fibrosis score to determine the likelihood of liver fibrosis, and second-line tests such as serum markers (e.g. ELF) and imaging modalities (e.g. ARFI elastography/FibroScan) 1. It is essential to note that liver disease can develop silently, and abnormal LFTs may not always be indicative of significant liver disease 1. Therefore, a thorough clinical evaluation and additional testing may be necessary to determine the underlying cause of elevated LFTs.

From the Research

Evaluation of Elevated Liver Enzymes

When evaluating elevated liver enzymes, the approach should be guided by both the clinical presentation and the pattern of injury 2. The following steps can be taken:

• Determine the clinical presentation and pattern of injury
• Order liver function tests (LFTs) to assess and monitor several diseases, including hepatocellular, cholestatic, or functioning liver diseases 3
• Interpret the results of LFTs, considering that abnormalities may not reflect liver disease 3

Diagnostic Approach

The diagnostic approach to elevated LFTs can be extensive or focused 4. The extensive approach involves testing for all diseases at once, while the focused approach involves testing for common diseases first. The choice of approach depends on the pre-test probabilities and prior evaluations performed.

• 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 becomes the most cost-effective strategy when accounting for pre-test probabilities and prior evaluations performed, and it can prevent false positives 4

Laboratory Tests

The following laboratory tests can be ordered to evaluate elevated LFTs:

• Liver function tests (LFTs), including hepatocellular, cholestatic, or functioning liver diseases 3
• Tests for common causes of abnormal LFTs, such as non-alcoholic fatty liver changes, Gilbert's disease, acute infectious hepatitis, alcoholic liver disease, and cirrhosis and hepatotoxic drug injury 5
• Biochemical tests, including alanine aminotransferase, to assess the magnitude of enzymatic elevation 6

Algorithmic Approach

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 6. This approach can assist providers in ensuring appropriate management and evaluation of the patient with elevated LFTs.

• Assess the magnitude of enzymatic elevation
• Correlate laboratory findings to the patient's clinical presentation
• Narrow the spectrum of a differential diagnosis based on the pattern of injury and clinical presentation 6