What are the first-line investigations for a patient with yellow stool, elevated conjugated bilirubin (direct bilirubin), and no abdominal pain, and what does high conjugated bilirubin suggest?

From the Guidelines

For a patient with yellow stool, elevated bilirubin, and no abdominal pain, the first-line investigations should include liver function tests (ALT, AST, ALP, GGT), complete blood count, abdominal ultrasound, and direct/indirect bilirubin fractionation, as these tests can help identify the underlying cause of the elevated bilirubin levels and guide further management. Elevated conjugated (direct) bilirubin suggests an obstruction in bile flow or a problem with bile excretion, such as choledocholithiasis or biliary ductal dilatation, which can be further evaluated with contrast-enhanced MRI with MRCP if necessary 1. The initial workup helps determine if the issue is obstructive (like gallstones or tumors blocking the bile ducts) or hepatocellular (liver cell damage). Key points to consider in the initial evaluation include:

• Liver function tests to assess the extent of liver damage or dysfunction
• Complete blood count to rule out infection or inflammation
• Abdominal ultrasound to visualize the biliary tree and identify potential obstructions or masses
• Direct/indirect bilirubin fractionation to determine the type of bilirubin elevation and guide further testing The absence of abdominal pain points away from acute cholecystitis but doesn't rule out other biliary obstructions, and contrast-enhanced MRI with MRCP may be useful in evaluating the etiology of biliary obstruction if extra- or intrahepatic biliary ductal dilatation is identified on abdominal US 1. Yellow stool specifically suggests impaired bile flow into the intestine, as bile gives stool its normal brown color, and prompt investigation is important as prolonged cholestasis can lead to complications including pruritus, malabsorption of fat-soluble vitamins, and potential liver damage.

From the Research

Initial Investigations

• If a patient's stool is yellow, bilirubin is raised, and there is no abdominal pain, the first line of investigation should include liver function tests, such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin 2
• The evaluation of abnormal liver chemistries should include fractionation of total bilirubin to direct and indirect bilirubin fractions 2

High Conjugated Bilirubin

• High conjugated bilirubin implies hepatocellular disease or biliary obstruction in most settings 2
• It can also suggest cholestasis, which is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 2
• The presence of an elevated conjugated bilirubin should prompt further investigation, including testing for viral hepatitis, nonalcoholic fatty liver disease, alcoholic liver disease, and other liver diseases 2
• A liver biopsy may be considered when serologic testing and imaging fail to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 2

Diagnostic Approach

• The diagnostic approach should consider the pattern of liver enzyme elevation, with hepatocellular injury defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels, and cholestatic injury defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 2
• The degree of elevation of ALT and/or AST in the clinical setting helps guide the evaluation 2
• It is essential to update the diagnostic algorithm when pathological liver function tests are detected, considering the increasing incidence of liver disease and rising mortality from liver causes in many European countries 3