What is the initial workup for a patient with elevated Liver Function Tests (LFTs) in a primary care setting?

Initial Workup for Elevated Liver Function Tests in Primary Care

Begin with a focused clinical history and standard liver aetiology screen (core panel), followed by risk stratification using FIB-4 score to determine need for specialist referral. 1

Clinical History and Physical Examination

Obtain specific details about:

• Alcohol consumption: quantify in units per week (>21 drinks/week for men, >14 drinks/week for women is significant); consider AUDIT-C screening 1, 2
• Metabolic risk factors: central obesity, hypertension, diabetes/insulin resistance, dyslipidemia 1, 2
• Medication history: capture all hepatotoxic medications including methotrexate (duration and cumulative dose), supplements, and over-the-counter drugs 1
• Country of origin: strongest predictor of viral hepatitis in the BALLETS study 1, 3
• Risk factors for viral hepatitis: intravenous drug use, sexual history, tattoos 3
• Family history: autoimmune disease, liver disease, hemochromatosis 1

Physical examination should document:

• Body mass index and abdominal examination for hepatosplenomegaly, ascites, and signs of chronic liver disease 1

Standard Liver Aetiology Screen (Core Panel)

Order the following tests simultaneously 1:

• Abdominal ultrasound 1
• Hepatitis B surface antigen (HBsAg) 1
• Hepatitis C antibody (with reflex PCR if positive) 1
• Autoimmune markers: anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody 1
• Serum immunoglobulins 1
• Simultaneous serum ferritin and transferrin saturation 1
• Complete blood count with platelets 2
• Fasting glucose and lipid profile 2

Important caveat: Do not simply repeat LFTs without investigating the cause, as 84% remain abnormal at 1 month and 75% at 2 years 4. The BALLETS study showed that determining the underlying cause is more important than serial monitoring 1.

Risk Stratification with FIB-4 Score

Calculate FIB-4 automatically using age, AST, ALT, and platelet count 1, 2:

FIB-4 Interpretation and Management:

• FIB-4 <1.3 (<2.0 if age >65 years): Low risk of advanced fibrosis

  • Negative predictive value ≥90% 1
  • No immediate specialist referral needed 1
  • Repeat FIB-4 in 2-3 years 1
  • Manage metabolic risk factors and lifestyle modifications in primary care 2

• FIB-4 1.3-2.67: Indeterminate risk

  • Requires second-tier testing with liver stiffness measurement (transient elastography/FibroScan) or Enhanced Liver Fibrosis (ELF) test 1, 2
  • Can be ordered as point-of-care test or as part of hepatology referral depending on local resources 1

• FIB-4 >2.67: High risk of advanced fibrosis

  • Positive predictive value 60-80% 1
  • Refer to hepatology for liver stiffness measurement or liver biopsy 1, 2

Immediate Specialist Referral Criteria

Refer urgently to hepatology if 1:

• Hepatitis B surface antigen positive 1
• Hepatitis C antibody positive (then PCR positive) 1
• Evidence of autoimmune hepatitis (raised IgG ± positive autoantibodies) 1
• Primary biliary cholangitis (cholestatic enzymes + positive anti-mitochondrial antibody) 1
• Primary sclerosing cholangitis suspected (cholestatic enzymes ± inflammatory bowel disease history) 1
• Hemochromatosis (raised ferritin AND transferrin saturation >45%) 1
• Dilated bile ducts on ultrasound 1
• ALT >1000 U/L (consider acute viral hepatitis including hepatitis A, E, cytomegalovirus) 1

Common Pitfalls to Avoid

Isolated elevated ferritin: This is commonly seen in dysmetabolic iron overload syndrome (NAFLD, alcohol excess) and does NOT reflect hemochromatosis unless transferrin saturation is also >45% 1

Viral hepatitis testing strategy: The BALLETS study showed that testing all patients from countries where viral hepatitis is prevalent is more cost-effective than repeating LFTs and waiting 3. A notably raised ALT (>2× upper limit of normal) has high predictive value but misses half the cases 3.

NAFLD prevalence: Nearly 40% of adults with abnormal LFTs have fatty liver on ultrasound, making it the most common diagnosis 1. However, only 1.3% of patients with abnormal LFTs in primary care have a specific liver disease requiring immediate treatment 1.

Lifestyle Counseling for NAFLD/Metabolic Liver Disease

If NAFLD is identified, recommend 2:

• Weight loss of 7-10% as cornerstone of treatment 2
• Mediterranean diet 2
• Regular physical activity (aerobic and/or resistance training) 2
• Complete alcohol abstinence if significant fibrosis present 2
• Optimize control of diabetes, hypertension, and dyslipidemia 2