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

Initial Workup for Elevated Liver Function Tests

The initial workup for elevated liver function tests should include a comprehensive hepatitis panel, assessment of alcohol use, medication review, and abdominal ultrasound, followed by targeted testing based on the pattern of elevation and clinical context. 1

Step 1: Initial Laboratory Assessment

• Obtain complete liver function panel including ALT, AST, alkaline phosphatase, bilirubin (total and direct), albumin, and prothrombin time/INR to determine the pattern of liver injury (hepatocellular vs. cholestatic) and assess synthetic function 1
• Complete blood count to evaluate for potential hematologic disorders or evidence of portal hypertension (thrombocytopenia) 1
• Renal function tests (BUN, creatinine) as these are prognostic markers in liver disease 1

Step 2: Pattern Recognition and Classification

Hepatocellular Pattern (Predominant elevation of aminotransferases)

• Mild elevation (<5× ULN): Consider NAFLD, alcohol-related liver disease, medication-induced injury, chronic viral hepatitis 1, 2
• Moderate to severe elevation (>5× ULN): Consider acute viral hepatitis, drug-induced liver injury, autoimmune hepatitis, ischemic injury 1

Cholestatic Pattern (Predominant elevation of alkaline phosphatase)

• Confirm hepatic origin by checking gamma-glutamyl transferase (GGT) 3
• Distinguish between intrahepatic and extrahepatic causes 1

Mixed Pattern (Elevation of both aminotransferases and alkaline phosphatase)

• Consider infiltrative diseases, drug-induced liver injury, or multiple concurrent processes 2

Step 3: Etiologic Evaluation

• Viral hepatitis panel: HBsAg, hepatitis B surface antibody, hepatitis B core antibody (HBcAb), HBcAb IgM (for acute hepatitis), and HCV antibodies 1
• Alcohol assessment: Detailed history, AST/ALT ratio (>2 suggests alcoholic liver disease in absence of cirrhosis) 1
• Medication and supplement review: Identify potential hepatotoxic agents 1
• Metabolic workup if indicated:
  • Iron studies (ferritin, transferrin saturation) for hemochromatosis 2
  • Ceruloplasmin for Wilson's disease 2
  • Alpha-1 antitrypsin levels 2
  • Autoimmune markers (ANA, ASMA, ANCA) if suspicion for autoimmune hepatitis 1

Step 4: Imaging Studies

• Abdominal ultrasound: First-line imaging to assess liver parenchyma, biliary tract, and exclude obstruction; specificity for excluding obstruction ranges from 71-97% 1
• Consider advanced imaging based on clinical context:
  • MRI with MRCP if suspicion for primary sclerosing cholangitis, primary biliary cholangitis, or if ultrasound is inconclusive 1
  • Triphasic CT or MRI if concern for hepatocellular carcinoma, especially with elevated AFP 1

Special Considerations

• For patients with normal or near-normal baseline ALT (<1.5× ULN), ALT elevation ≥5× ULN warrants close monitoring even without symptoms 1
• For patients with elevated baseline ALT (≥1.5× ULN), ALT elevation >3× baseline or >300 U/L should raise suspicion for new liver injury 1
• Combination of ALT elevation with elevated bilirubin (ALT ≥3× ULN plus bilirubin ≥2× ULN) is particularly concerning and requires urgent evaluation 1

Common Pitfalls to Avoid

• Relying solely on liver enzyme levels for diagnosis - LFTs have poor sensitivity and specificity for specific liver diseases 3, 4
• Failure to consider non-hepatic causes of abnormal LFTs (e.g., muscle disease causing AST elevation) 1, 3
• Over-investigation of mild, isolated LFT abnormalities in asymptomatic patients - consider monitoring for 3-6 months before extensive workup 2
• Using standard laboratory reference ranges without considering patient context - current upper limits of normal may not be optimal for detecting early disease 4

When to Consider Liver Biopsy

• Persistent unexplained elevation of liver enzymes despite negative non-invasive workup 1
• Suspected autoimmune hepatitis, primary biliary cholangitis, or non-alcoholic steatohepatitis requiring confirmation 1
• Discordant clinical, laboratory, and imaging findings 1
• Evaluation of hepatic fibrosis stage when this would impact management decisions 1