Malignant biliary strictures in patients with a normal bilirubin and/or normal liver enzymes

To date, no studies have sought to determine the frequency of malignancy in patients presenting with a putative biliary stricture and normal liver function tests (LFTs). The primary aim of this retrospective cohort study was to determine the likelihood of malignancy in patients presenting with a biliary stricture and normal LFTs, a normal bilirubin level either alone or in combination with normal levels of liver enzymes [alkaline phosphatase (ALP) and alanine transaminase (ALT)]. A secondary aim was to determine any clinical/biochemical/sonographic features that may be associated with malignancy.

Patients presenting over a 10-year period were included. Fifteen variables were analysed to determine their association with malignant disease.

Eight hundred and thirty patients with putative biliary strictures were included. Primary hepatopancreaticobiliary (HPB) cancers presented with a normal bilirubin and normal liver enzymes (ALP and ALT) in 6% of cases. Patients with a putative biliary stricture and a normal bilirubin level whose final diagnoses were pancreatic cancer, ampullary cancer, distal cholangiocarcinoma and hilar cholangiocarcinoma represented 21%, 13%, 7% and 9% of individuals diagnosed with these pathologies, respectively. Hypoalbuminaemia and isolated intrahepatic duct dilatation on ultrasound were significantly associated with malignancy in patients with normal bilirubin and completely normal LFTs.

This study has shown that patients with a putative biliary stricture and completely normal LFTs are unlikely to have a primary HPB malignancy. Those presenting with a normal bilirubin level, but deranged liver enzymes (ALP and/or ALT), are more likely to have malignant disease, and this should necessitate a higher degree of clinical suspicion.