Laboratory Testing for Newly Elevated Liver Enzymes
Order a comprehensive initial panel including bilirubin, albumin, ALT, AST, alkaline phosphatase, GGT, complete blood count, hepatitis B surface antigen, hepatitis C antibody (with reflex PCR), anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, serum immunoglobulins, simultaneous serum ferritin and transferrin saturation, and abdominal ultrasound. 1, 2
Core Initial Laboratory Panel
The standard liver etiology screen should include the following tests ordered simultaneously 1, 3:
Basic liver function tests:
- Bilirubin 1
- Albumin 1
- Alanine aminotransferase (ALT) 1
- Aspartate aminotransferase (AST) 1
- Alkaline phosphatase (ALP) 1
- γ-glutamyltransferase (GGT) 1
- Prothrombin time/INR 2
Viral hepatitis screening:
- Hepatitis B surface antigen (HBsAg) 1, 4
- Hepatitis C antibody with automatic reflex to PCR if positive 1, 4
Autoimmune markers:
- Anti-mitochondrial antibody 1
- Anti-smooth muscle antibody 1
- Antinuclear antibody 1
- Serum immunoglobulins 1
Iron studies (must be drawn simultaneously):
Additional baseline tests:
Essential Imaging
Abdominal ultrasound should be obtained immediately to assess liver parenchyma, evaluate for fatty infiltration, detect biliary tract abnormalities, and identify hepatosplenomegaly or focal lesions 1, 2. This imaging is part of the standard liver etiology screen and should not be delayed 1.
Pattern Recognition Before Ordering
Before finalizing your test selection, determine the pattern of elevation to guide additional testing 2, 5:
- Hepatocellular pattern (predominant ALT/AST elevation): ALT:AST ratio >1 suggests non-alcoholic causes, while AST:ALT ratio >1 suggests alcoholic liver disease 2
- Cholestatic pattern (predominant ALP/GGT elevation): Consider adding MRCP if inflammatory bowel disease or autoimmune history present to evaluate for primary sclerosing cholangitis 2
- Marked elevation (ALT >1000 U/L): Add acute viral hepatitis serologies including hepatitis A IgM, hepatitis E IgM, and CMV serology 2, 4
Risk Stratification for NAFLD
If metabolic syndrome features are present (central obesity, hypertension, diabetes, dyslipidemia), calculate FIB-4 or NAFLD Fibrosis Score using the initial laboratory results to determine fibrosis risk 1, 3. This calculation should be incorporated into your workflow as NAFLD accounts for approximately 40% of abnormal liver tests in developed countries 3.
Critical Clinical Context to Document
Document the following to interpret results appropriately 2, 3:
- Complete medication review including prescribed drugs, over-the-counter medications, herbal supplements, and illicit drugs 2, 3
- Quantified alcohol consumption using AUDIT-C screening 3
- Age, ethnicity, and country of birth for hepatitis B/C risk assessment 3
- Metabolic syndrome features: BMI, waist circumference, blood pressure 2, 3
- Symptoms: jaundice, abdominal pain, weight loss, pruritus, fever 2
Common Pitfalls to Avoid
Do not simply repeat the same abnormal liver tests without pursuing the underlying etiology, as 84% of abnormal liver tests remain abnormal at 1 month and 75% at 2 years 3, 4. The extent of liver blood test abnormality is not necessarily a guide to clinical significance—interpretation requires review of previous results, past medical history, and current medical condition 1.
All patients with abnormal liver blood tests should be considered for investigation with a liver aetiology screen irrespective of level and duration of abnormality 1. Abnormal refers to any analyte outside the laboratory reference range 1.
Urgent Referral Triggers
Refer immediately to hepatology if initial results show 2, 3: