What is the further lab workup for a patient with hyperbilirubinemia, elevated alkaline phosphatase (alk phos), and elevated liver enzymes, specifically alanine transaminase (ALT) and aspartate transaminase (AST)?

From the Guidelines

For a patient with hyperbilirubinemia, elevated alkaline phosphatase, and elevated liver enzymes (ALT and AST), I recommend a comprehensive hepatobiliary workup, starting with abdominal ultrasound to evaluate for biliary obstruction, followed by additional imaging and laboratory testing as indicated by the clinical scenario. The patient's laboratory findings suggest liver dysfunction that could result from various etiologies, including viral hepatitis, autoimmune disorders, biliary obstruction, medication toxicity, or alcoholic liver disease 1. Given the elevated alkaline phosphatase, it is essential to confirm its hepatobiliary origin with gamma glutamyl transferase and/or alkaline phosphatase isoenzyme fractionation 1. The pattern of elevated bilirubin with increased alkaline phosphatase suggests a possible cholestatic component, while elevated transaminases (ALT, AST) indicate hepatocellular injury. Some key considerations for the workup include:

• Complete hepatitis panel (A, B, C) to evaluate for viral hepatitis 1
• Autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody) to assess for autoimmune disorders 1
• Ceruloplasmin to rule out Wilson's disease, iron studies, and alpha-1 antitrypsin levels to evaluate for other potential causes of liver dysfunction 1
• Imaging studies such as MRCP (magnetic resonance cholangiopancreatography) if obstruction is suspected, or CT scan with contrast, MRI with contrast to evaluate for other potential causes of liver dysfunction 1 While awaiting results, the patient should avoid alcohol and hepatotoxic medications, including acetaminophen 1. Ursodeoxycholic acid at 13-15 mg/kg/day may be considered for cholestatic conditions 1. It is crucial to note that the extent and type of work-up may vary by patient's history, severity of liver injury, underlying disease, and geography 1. A thorough history and physical examination are essential to guide the diagnostic workup and management plan. In patients with significant symptoms, evidence of chronic or decompensated liver disease, or severe liver chemistry abnormalities, a complete and expeditious evaluation is essential 1.

From the Research

Further Lab Workup for Hyperbilirubinemia and Elevated Liver Enzymes

The following steps can be taken for further lab workup:

• Evaluate the pattern of liver test abnormalities to suggest the underlying cause of liver disease, such as hepatitis, biliary obstructions, or infiltrative liver disease 2
• Assess the origin of the alkaline phosphatase elevation by evaluating GGT levels to confirm the hepatic origin 3
• Distinguish between extrahepatic (biliary obstruction) or intrahepatic (PBC, PSC, drugs, etc.) cholestasis using abdominal ultrasound to evaluate the biliary system 3
• Evaluate albumin and prothrombin levels to assess hepatic function and differentiate between acute and chronic diseases 3
• Consider non-invasive diagnostic tests, such as serology, iron levels, autoimmunity, or abdominal ultrasound, to aid in diagnosis 3, 4

Specific Tests for Hyperbilirubinemia

For hyperbilirubinemia, the following tests can be considered:

• Fractionation of bilirubin to distinguish between conjugated and unconjugated hyperbilirubinemia 3
• Evaluation of hemolysis, ineffective erythropoiesis, Gilbert or Crigler-Najjar syndromes for non-conjugated hyperbilirubinemia 3
• Consideration of Rotor and Dubin-Johnson Syndromes for conjugated hyperbilirubinemia 3

Additional Considerations

Additional considerations for patients with abnormal liver tests include:

• Detailed history gathering and alcohol use assessment 4
• Recognition of metabolic syndrome 4
• Identification of patterns of liver test abnormalities to develop a systematic approach to address abnormal liver tests 4