From the Guidelines
The workup for elevated direct bilirubin and transaminases should begin with a thorough history and physical examination, followed by laboratory and imaging studies to determine the underlying cause, as recommended by the most recent guidelines 1. The initial step in evaluating elevated direct bilirubin and transaminases is to assess the patient's clinical presentation and medical history, including any potential exposures to hepatotoxic substances or medications.
- Initial laboratory tests should include a complete liver panel (ALT, AST, alkaline phosphatase, GGT, total and direct bilirubin), complete blood count, coagulation studies (PT/INR), and albumin, as suggested by 1.
- Viral hepatitis serologies (hepatitis A, B, C, E) should be ordered, along with autoimmune markers including ANA, anti-smooth muscle antibody, anti-mitochondrial antibody, and immunoglobulin levels, to rule out autoimmune hepatitis and viral hepatitis, as recommended by 1.
- Metabolic and genetic testing may include ceruloplasmin, alpha-1 antitrypsin, iron studies, and genetic testing for conditions like Wilson's disease or hemochromatosis, as mentioned in 1. Imaging typically starts with an abdominal ultrasound with Doppler to assess liver parenchyma, biliary tract, and vascular patency.
- Depending on initial findings, further imaging such as CT, MRI/MRCP, or ERCP may be necessary to evaluate the biliary tract and liver parenchyma, as suggested by 1.
- In cases where the diagnosis remains unclear, a liver biopsy may be required for definitive diagnosis, as recommended by 1, to identify the underlying cause of the elevated liver enzymes and direct bilirubin. This systematic approach helps identify whether the elevation is due to hepatocellular injury, biliary obstruction, or a combination of both, guiding appropriate treatment and management, as emphasized by 1.
From the Research
Workup for Elevated Direct Bilirubin and Transaminase Levels
The workup for elevated direct bilirubin and transaminase levels involves a comprehensive medical history, review of systems, and physical examination to differentiate potential causes. Key steps in the workup include:
- Initial laboratory evaluation with assays for bilirubin (total and fractionated), complete blood cell count, aspartate transaminase, alanine transaminase, gamma-glutamyltransferase, alkaline phosphatase, albumin, prothrombin time, and international normalized ratio 2
- Measuring fractionated bilirubin to determine whether the hyperbilirubinemia is conjugated or unconjugated 2
- Imaging studies such as ultrasonography of the abdomen, computed tomography with intravenous contrast media, and magnetic resonance cholangiopancreatography to evaluate the liver and biliary tract 2, 3
- Consideration of potential causes such as alcoholic liver disease, biliary strictures, choledocholithiasis, drug-induced liver injury, hemolysis, or hepatitis 2, 4
- Evaluation of liver function using tests such as direct bilirubin, aspartate transaminase:alanine transaminase ratio, or model for end-stage liver disease (MELD) score 5
Laboratory Evaluation
Laboratory evaluation is crucial in the workup of elevated direct bilirubin and transaminase levels. Key laboratory tests include:
- Bilirubin (total and fractionated) to determine the level and type of hyperbilirubinemia 2
- Aminotransferases (aspartate transaminase and alanine transaminase) to evaluate liver cell injury 4
- Gamma-glutamyltransferase and alkaline phosphatase to evaluate cholestasis 4
- Albumin and prothrombin time to evaluate liver synthetic function 2
- International normalized ratio (INR) to evaluate coagulation 2
Imaging Studies
Imaging studies are essential in the workup of elevated direct bilirubin and transaminase levels. Key imaging studies include:
- Ultrasonography of the abdomen to evaluate the liver, gallbladder, and biliary tract 2
- Computed tomography with intravenous contrast media to evaluate the liver and biliary tract 2
- Magnetic resonance cholangiopancreatography to evaluate the biliary tract and pancreas 2
Potential Causes
Potential causes of elevated direct bilirubin and transaminase levels include: