Can a patient have normal bilirubin levels and elevated Liver Function Tests (LFTs) with cholelithiasis (gallstones)?

From the Guidelines

Yes, it is possible for a patient to have normal bilirubin levels and elevated Liver Function Tests (LFTs) with cholelithiasis (gallstones). According to the 2020 World Society of Emergency Surgery guidelines 1, elevated LFTs or bilirubin are not sufficient for the diagnosis of common bile duct stones (CBDS) in patients with acute calculus cholecystitis (ACC). The guidelines recommend against relying solely on elevated LFTs or bilirubin for diagnosis, suggesting that further diagnostic tests are necessary.

Key Points to Consider

• Normal LFTs have a high negative predictive value (NPV) of 97%, but the positive predictive value (PPV) of abnormal LFTs is only 15% 1.
• The elevation of LFTs is a poor tool for predicting CBDS, with literature ranging from 25 to 50% 1.
• In patients with ACC, LFTs may be altered due to the acute inflammatory process rather than direct biliary obstruction, with 15-50% of patients showing elevation in LFTs without CBDS 1.
• Specificity of serum bilirubin levels for CBDS is 60% with a cut-off level of 1.7 mg/day and 75% with a cut-off level of 4 mg/dl, but mean bilirubin levels in patients with CBDS are generally lower (1.5 to 1.9 mg/dl) 1.

Clinical Implications

• The presence of gallstones can cause inflammation or irritation of the gallbladder and surrounding tissues, leading to elevated liver enzymes such as ALT, AST, ALP, and GGT, even in the absence of bile duct obstruction.
• Patients with normal bilirubin but elevated LFTs and known gallstones may still require treatment, especially if symptomatic.
• Treatment options include laparoscopic cholecystectomy for symptomatic patients, while asymptomatic patients might be monitored with regular follow-ups.
• The absence of elevated bilirubin does not rule out significant gallstone disease, as complete obstruction is not necessary for gallstones to cause symptoms or inflammation.

From the Research

Patient Profile with Normal Bilirubin Levels and Elevated LFTs

• Patients with cholelithiasis (gallstones) can have normal bilirubin levels and elevated Liver Function Tests (LFTs) 2, 3, 4.
• A study published in 2009 found that out of 124 patients with symptomatic cholelithiasis, 108 (87.10%) had normal LFTs, while 16 (12.90%) had deranged LFTs 2.
• Another study from 1995 reported five patients with choledocholithiasis (common bile duct stones) who had normal serum liver enzyme and total bilirubin levels 3.

Liver Function Test Patterns

• The pattern of LFT elevation can vary in patients with obstructive jaundice due to biliary strictures or stones 5.
• In patients with malignant strictures, alkaline phosphatase (ALP) levels tend to be higher than aspartate transaminase (AST) levels 5.
• However, in patients with common bile duct stones, AST and ALP levels can be similarly elevated, and AST may even exceed ALP during maximum jaundice or painful episodes 5.

Diagnostic Considerations

• Normal liver enzymes should not dissuade clinicians from performing cholangiography in patients with suspected choledocholithiasis 3.
• Patients with biliary-like pain and normal findings on cholecystogram and ultrasound study of the gallbladder should be evaluated further by diagnostic ERCP examination if they have abnormal liver function test results 4.
• The possibility of extrahepatic biliary obstruction should be considered even when AST is the predominantly elevated enzyme 5.