Which laboratory tests should be ordered for a patient with known cirrhosis who now presents with pruritus?

Laboratory Evaluation for Cirrhosis with Pruritus

Order liver function tests (ALT, AST, alkaline phosphatase, GGT, bilirubin), serum bile acids, and antimitochondrial antibodies immediately, as pruritus in cirrhosis signals cholestasis requiring specific diagnostic workup and treatment. 1

Essential Initial Laboratory Panel

Core Cholestatic Markers

• Liver function tests (LFTs) including ALT, AST, alkaline phosphatase, GGT, and total bilirubin should be ordered first, as these identify the pattern and severity of cholestasis in cirrhotic patients with pruritus 1, 2
• Serum bile acids (non-fasting) are the most sensitive marker for cholestasis and should be measured even when standard LFTs appear normal, since bile acids can be elevated before other abnormalities appear 2, 3
  • Normal bile acids are typically <10-11 μmol/L 2
  • Elevated bile acids (≥11 μmol/L) confirm cholestatic component driving pruritus 2

Autoimmune and Etiology Screening

• Antimitochondrial antibodies (AMA) should be checked to screen for primary biliary cholangitis, which commonly presents with pruritus and can coexist with or complicate cirrhosis 1, 2
• Complete blood count (CBC) and ferritin should be obtained, as iron deficiency can cause or worsen pruritus independent of liver disease 1

Secondary Investigations Based on Initial Results

If Cholestasis Confirmed

• Hepatobiliary ultrasound to exclude biliary obstruction or gallstones that may be contributing to cholestasis 4
• Repeat bile acids weekly if symptoms persist with initially normal results, as bile acids can rise rapidly in progressive cholestatic disease 2, 3

If Hematologic Concerns

• Blood film, lactate dehydrogenase (LDH), and erythrocyte sedimentation rate (ESR) if suspicion of polycythemia vera (aquagenic pruritus) or lymphoma (night sweats, weight loss, lymphadenopathy) 1
• JAK2 V617F mutation analysis if elevated hemoglobin/hematocrit suggests polycythemia vera 1

If Infectious Etiology Suspected

• Hepatitis A, B, and C serology should be considered, as chronic hepatitis C with moderate-to-severe fibrosis can cause low-grade cholestasis with pruritus and bile duct injury 1, 5
• HIV serology if risk factors present 1

Critical Pitfalls to Avoid

• Do not assume pruritus is benign in cirrhosis—it signals cholestasis requiring specific treatment with ursodeoxycholic acid or rifampicin, not just antihistamines 2, 6
• Do not skip bile acid testing even if standard LFTs are only mildly elevated, as bile acids are more sensitive for cholestasis and guide treatment intensity 2
• Do not overlook iron deficiency, which is the most common systemic cause of pruritus and responds rapidly to iron replacement 1
• Do not delay imaging if alkaline phosphatase or GGT are disproportionately elevated, as biliary obstruction requires urgent intervention 7

Interpretation Algorithm

If alkaline phosphatase/GGT elevated disproportionately to ALT/AST:

• Cholestatic pattern confirmed → proceed with bile acids, AMA, and ultrasound 1, 7

If bile acids >11 μmol/L with cholestatic LFTs:

• Initiate ursodeoxycholic acid 10-20 mg/kg/day for symptom relief 2
• Consider rifampicin 150 mg twice daily (titrate to 600 mg twice daily) as first-line for hepatic pruritus if cholestasis confirmed 2

If AMA positive:

• Diagnose primary biliary cholangitis and refer to hepatology for disease-specific management 1, 6

If all labs normal but pruritus persists:

• Repeat bile acids and LFTs in 2-4 weeks, as pruritus can precede laboratory abnormalities by several weeks in cholestatic conditions 2
• Check ferritin and consider trial of iron replacement if <25 μg/L 1