What laboratory tests are a good assessment for liver function?

Laboratory Tests for Liver Function Assessment

The initial investigation for potential liver disease should include bilirubin, albumin, ALT, ALP, and GGT, together with a full blood count if not already performed within the previous 12 months. 1

Core Liver Function Tests

Tests Reflecting Hepatocellular Injury

• Alanine Aminotransferase (ALT): Primary marker of hepatocellular damage
• Aspartate Aminotransferase (AST): Additional marker of liver cell injury
• Gamma-Glutamyl Transferase (GGT): Increases sensitivity for detecting liver disease when combined with other tests

Tests Reflecting Cholestasis

• Alkaline Phosphatase (ALP): Indicates biliary obstruction or cholestatic liver disease
• Gamma-Glutamyl Transferase (GGT): Helps confirm hepatic origin of elevated ALP

Tests Reflecting Synthetic Function

• Albumin: Exclusively produced by the liver; reflects medium to long-term synthetic function 2
• Prothrombin Time (PT)/International Normalized Ratio (INR): Measures clotting factor synthesis; reflects acute liver synthetic function

Tests Reflecting Excretory Function

• Bilirubin (Total and Direct): Measures liver's ability to uptake, conjugate, and excrete bilirubin

Rationale for Test Selection

The Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study found that ALT and ALP identified the vast majority of adults with liver disease 1. The addition of GGT increased sensitivity but with some loss of specificity. However, GGT is valuable for detecting alcohol-related liver disease (ARLD) and non-alcoholic fatty liver disease (NAFLD), which account for 90% of liver mortality 1.

Pattern Recognition in Liver Disease

Hepatocellular Pattern

• Predominant elevation of transaminases (ALT/AST) >5× upper limit of normal (ULN)
• ALP usually increased <2-3× ULN
• Suggests viral hepatitis, drug-induced liver injury, autoimmune hepatitis

Cholestatic Pattern

• Predominant elevation of ALP >3-5× ULN
• Mild increase in transaminases
• Suggests biliary obstruction, primary biliary cholangitis, primary sclerosing cholangitis
• Exception: Cholestasis with cholangitis may show substantial transaminase elevation 3

Infiltrative Pattern

• Disproportionate elevation of ALP compared to bilirubin
• Suggests lymphoma, granulomatous hepatitis, metastatic disease 3

Extended Testing Based on Clinical Context

When initial tests suggest liver dysfunction, additional testing may include:

Viral Hepatitis Panel

• Hepatitis B surface antigen
• Hepatitis C antibody (with follow-on PCR if positive) 1

Iron Studies

• Ferritin
• Transferrin saturation 1

Autoimmune Markers

• Anti-mitochondrial antibody
• Anti-smooth muscle antibody
• Antinuclear antibody
• Serum immunoglobulins 1

Metabolic Disease Markers

• Alpha-1-antitrypsin level
• Ceruloplasmin (in patients age >3 and <40 years) 1

Assessing Liver Fibrosis

For patients with NAFLD or liver disease of unknown etiology:

1. Calculate non-invasive fibrosis scores (FIB-4 or NAFLD fibrosis score)
2. Consider second-line tests:
   • Serum markers (Enhanced Liver Fibrosis score)
   • Imaging (FibroScan/elastography) 1

Common Pitfalls in Liver Test Interpretation

1. Overreliance on ALT/AST alone: May miss cholestatic or infiltrative diseases
2. Ignoring GGT: Important for detecting ARLD and NAFLD
3. Misinterpreting isolated abnormalities: Single abnormal test may not indicate significant liver disease
4. Failing to recognize non-hepatic causes: ALP can be elevated in bone disease; AST in muscle injury
5. Overlooking normal tests in advanced disease: In cirrhosis, transaminases may normalize as hepatocyte mass decreases

Special Considerations

• Baseline abnormalities in oncology patients: Liver metastases can cause baseline elevations in liver tests; 31% of patients with liver metastases have ALT >ULN 1
• Age considerations: Higher cut-off points for fibrosis scores should be used for patients aged over 65 years 1
• Albumin interpretation: More a marker of inflammation than nutritional status in acute settings 2

By systematically applying these laboratory tests and understanding their patterns, clinicians can effectively assess liver function, identify the presence and type of liver disease, and monitor disease progression or treatment response.