A 58-year-old woman presents with 9 months of jaundice (yellowing of sclera and skin) accompanied by pruritus (skin itching). Physical exam shows marked jaundice, liver palpable 4 cm below the costal margin (hard consistency, no tenderness), and spleen palpable 5 cm below the costal margin. Primary biliary cirrhosis (PBC) is suspected. Which test is most diagnostic?