Management of Abnormal Liver Function Tests
When abnormal liver function tests are detected, the appropriate management is to determine the underlying cause rather than simply repeating the tests, as 84% remain abnormal after one month and 75% remain abnormal after two years. 1
Initial Assessment
Clinical History
- Age and ethnicity/country of birth (for hepatitis B/C risk)
- Symptoms: jaundice, abdominal pain, weight loss, pruritus
- Medication history: prescribed, over-the-counter, herbal remedies
- Alcohol consumption (current and past intake in units per week)
- Metabolic syndrome features (obesity, hypertension, diabetes, dyslipidemia)
- Travel history and occupational exposures
- Family history of liver disease
Physical Examination
- Body mass index calculation
- Abdominal examination for hepatosplenomegaly, ascites, and signs of chronic liver disease
Laboratory Investigation
Core Panel (First-line Testing)
- Complete blood count
- Hepatitis B surface antigen
- Hepatitis C antibody (followed by PCR if positive)
- Ferritin and transferrin saturation
- Immunoglobulins (IgG, IgA, IgM)
- Autoantibodies (ANA, SMA, LKM, AMA)
- Ceruloplasmin (if <55 years)
- Alpha-1-antitrypsin
Pattern Recognition
- Hepatocellular pattern: Predominant elevation of transaminases (ALT/AST)
- Cholestatic pattern: Predominant elevation of alkaline phosphatase and GGT
- Mixed pattern: Elevation of both transaminases and cholestatic markers
Imaging
- Ultrasound is the recommended first-line imaging for all patients with abnormal liver tests
- MRI may be required upfront for suspected primary sclerosing cholangitis
Referral Criteria
Immediate Referral
- Unexplained clinical jaundice
- Suspicion of hepatic or biliary malignancy
- ALT >1000 U/L (consider acute viral hepatitis, drug-induced liver injury)
Specialist Referral
- Positive hepatitis B surface antigen
- Positive hepatitis C antibody with positive PCR
- Autoimmune hepatitis (raised IgG ± positive autoantibodies)
- Primary biliary cholangitis (cholestatic enzymes + positive anti-mitochondrial antibody)
- Primary sclerosing cholangitis (cholestatic enzymes ± inflammatory bowel disease)
- Hemochromatosis (raised ferritin and transferrin saturation >45%)
- Dilated bile ducts on imaging
Important Considerations
Severity Assessment
- The extent of liver blood test abnormality is not necessarily a guide to clinical significance 1
- Many patients with significant liver fibrosis may have liver enzymes in the normal reference range 2
- Current upper limits of normal for liver enzymes may be too high, especially for ALT 1
Common Pitfalls
Repeating tests without investigation: Simply repeating abnormal tests without investigating the cause is only justified when there's high certainty the abnormality will resolve due to an identified acute insult 1
Assuming mild abnormalities are benign: Common causes of chronic liver disease (NAFLD, alcohol-related liver disease, hepatitis C) often present with only mild or moderate liver test abnormalities 1
Normalizing values indicating resolution: Even normalized liver blood tests do not necessarily imply absence or resolution of disease in conditions like hepatitis C and NAFLD 1
Missing pediatric cases: Children should have a lower threshold for referral to a pediatrician as the differential diagnosis differs from adults 1
By following this structured approach to abnormal liver function tests, clinicians can ensure timely diagnosis and management of potentially serious liver conditions, preventing progression to end-stage liver disease.