Initial Liver Blood Test Panel
For initial investigation of potential liver disease, order bilirubin, albumin, ALT, ALP, and GGT, along with a complete blood count if not performed within the past 12 months. 1
Core Panel Components
The standard initial liver panel should include:
- Bilirubin: Measures the liver's ability to process waste products and indicates cholestatic or hepatocellular dysfunction 2
- Albumin: Assesses synthetic liver function and helps distinguish acute from chronic disease 2
- Alanine aminotransferase (ALT): Primary marker for hepatocellular injury, most specific for liver damage 1, 2
- Alkaline phosphatase (ALP): Indicates biliary disease and cholestatic patterns 2
- Gamma-glutamyltransferase (GGT): Increases sensitivity for detecting alcohol-related and non-alcoholic fatty liver disease, which account for 90% of liver mortality 1, 2
- Complete blood count (CBC): Essential to assess platelet count, as thrombocytopenia indicates advanced liver disease with portal hypertension 2
Why This Specific Panel
The British Society of Gastroenterology guidelines are based on the BALLETS study, which demonstrated that ALT and ALP identify the vast majority of adults with liver disease. 1 While adding GGT increases sensitivity from 15% to 30% for detecting abnormal liver tests, it does so with marginal loss of specificity—but this trade-off is justified because elevated GGT is associated with increased liver-specific and all-cause mortality. 1
Important caveat: AST is deliberately excluded from the initial panel because routine addition did not improve detection of specific disease in the BALLETS analysis. 1 However, AST becomes critical for subsequent risk stratification (see below).
Additional Testing Based on Initial Results
If Initial Tests Are Abnormal
Order a reflex AST on the same sample to calculate the AST:ALT ratio, which assesses fibrosis risk without requiring a new blood draw. 1, 2 An AST:ALT ratio >1 indicates advanced fibrosis or cirrhosis, even when both values are within normal range. 1, 2
Consider adding PT/INR to evaluate synthetic liver function, particularly if suspecting acute liver injury or cirrhosis. 2
Standard Liver Aetiology Screen (Second-Line Testing)
When any liver test is abnormal (outside laboratory reference range), proceed with a complete aetiology screen regardless of the degree of abnormality. 1 This is a critical point: even mild elevations warrant investigation, as the extent of abnormality does not predict clinical significance. 1
For adults, the standard aetiology screen includes: 1, 2
- Abdominal ultrasound
- Hepatitis B surface antigen
- Hepatitis C antibody (with reflex PCR if positive)
- Anti-mitochondrial antibody
- Anti-smooth muscle antibody
- Antinuclear antibody
- Serum immunoglobulins
- Ferritin and transferrin saturation (simultaneous measurement)
For children, modify the panel to include: 1
- Anti-liver kidney microsomal antibody
- Coeliac antibodies
- Alpha-1-antitrypsin level
- Caeruloplasmin (age >3 years)
High-Risk Populations: Simultaneous Testing
In high-risk groups (injecting drug users, migrants from high-prevalence areas, prisoners), order viral hepatitis screening simultaneously with the initial panel rather than waiting for abnormal results. 1, 2 This approach is more cost-effective and prevents delays in identifying immediately treatable causes. 3
Common Pitfalls to Avoid
Do not assume normal liver tests exclude significant disease: Both AST and ALT can be normal even in cirrhosis. 1, 2 The AST:ALT ratio remains useful for risk stratification even when both enzymes are within normal limits. 1
Do not simply repeat abnormal tests without pursuing etiology: 75% of abnormal liver enzymes remain abnormal at 2 years, making watchful waiting inappropriate. 3 Any abnormality warrants investigation. 1
Always interpret results in clinical context: Review previous results, past medical history, and current medications before acting on abnormal values. 1 The pattern of abnormality (hepatocellular vs. cholestatic) guides subsequent workup more than the absolute values. 1
Do not order "liver function tests" expecting functional assessment: Most routine tests measure hepatocellular damage, not function. 4 True functional tests are albumin, PT/INR, and bilirubin. 4, 5
Cost-Effective Strategy
Implement "reflex" testing protocols where AST is automatically run on the same sample if ALT or GGT is abnormal, avoiding the need for patient recall and additional venipuncture. 1, 2 This approach is being piloted in Wales and Scotland with promising preliminary results. 1