From the Guidelines
The workup for elevated liver function tests (LFTs) should begin with a thorough history and physical examination, focusing on risk factors for liver disease, and initial laboratory testing should include a complete metabolic panel, complete blood count, and a hepatitis panel (A, B, and C) as recommended by 1. The initial assessment should also include calculation of a FIB4 or NAFLD fibrosis score with values <1.3 and ≤1.455, respectively, signifying a low risk of advanced fibrosis, as suggested by 1. Key points to consider in the history include:
- Alcohol use
- Medications
- Family history
- Symptoms Additional tests may include:
- Iron studies (ferritin, transferrin saturation)
- Ceruloplasmin for Wilson's disease
- Antimitochondrial antibodies for primary biliary cholangitis
- Anti-smooth muscle antibodies for autoimmune hepatitis
- Immunoglobulin levels An ultrasound of the liver should be performed to assess for structural abnormalities, fatty infiltration, or biliary obstruction, as recommended by 1. If the diagnosis remains unclear, further testing may include magnetic resonance cholangiopancreatography (MRCP) for detailed biliary imaging or a liver biopsy for definitive diagnosis, as suggested by 1. Patients should be advised to avoid alcohol and hepatotoxic medications during the evaluation, as recommended by 1. The pattern of LFT elevation can provide diagnostic clues:
- Predominantly elevated aminotransferases (ALT, AST) suggest hepatocellular injury
- Elevated alkaline phosphatase and bilirubin point toward cholestatic or obstructive processes Early diagnosis is crucial as many liver conditions respond better to treatment when identified early, as emphasized by 1.
From the Research
Evaluation of Elevated Liver Function Tests (LFTs)
Elevated LFTs are a common problem faced by physicians, and their evaluation is crucial for determining the underlying cause and guiding management. The following steps can be taken to evaluate elevated LFTs:
- Determine the etiology of the underlying liver disease 2
- Evaluate the severity of the liver dysfunction and determine if acute liver failure (ALF) or acute decompensation of chronic liver failure is present 2
- Look for the presence of associated complications, either those of ALF or chronic liver failure as appropriate 2
- Use an algorithmic approach to interpret abnormalities in LFTs, separating disease processes into hepatocellular, cholestatic, or functioning liver groupings 3
Laboratory Tests
The most common liver chemistries ordered are:
- Serum alanine aminotransferase (ALT)
- Aspartate aminotransferase (AST)
- Alkaline phosphatase
- Bilirubin 4 These tests can help determine the type of liver injury, such as hepatocellular or cholestatic injury 4
Diagnostic Approach
The diagnostic approach to elevated LFTs involves:
- Testing for viral hepatitis A, B, and C
- Assessment for nonalcoholic fatty liver disease and alcoholic liver disease
- Screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 4
- Evaluation of alkaline phosphatase elevation to determine if it is of hepatic origin, and testing for primary biliary cholangitis and primary sclerosing cholangitis if necessary 4
- Fractionation of total bilirubin elevation to direct and indirect bilirubin fractions to determine if it is due to hepatocellular disease or biliary obstruction 4
Follow-up and Management
Follow-up testing is crucial for patients with elevated LFTs, and the timing of repeat testing depends on the degree of abnormality 5
- Patients with mild abnormalities (1-2 times normal) may have a longer time to follow-up compared to those with severe abnormalities (>4 times normal) 5
- The implementation of electronic health records (EHRs) can reduce the time to repeat testing, but may not improve follow-up rates 5
- A liver biopsy may be considered when serologic testing and imaging fail to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 4