From the Guidelines
The workup for transaminitis and hyperbilirubinemia should begin with a thorough history, physical examination, and initial laboratory tests including complete liver function tests, complete blood count, and coagulation studies, as recommended by the most recent guidelines 1. The initial laboratory tests should include ALT, AST, alkaline phosphatase, GGT, total and direct bilirubin, albumin, and prothrombin time.
- Additional testing should include viral hepatitis serologies (hepatitis A, B, C) 1,
- autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody) 1,
- iron studies,
- ceruloplasmin (for Wilson's disease),
- alpha-1 antitrypsin levels, and
- screening for alcohol use disorder. Imaging studies are essential, starting with an abdominal ultrasound to evaluate for biliary obstruction, fatty liver, masses, or cirrhosis, as suggested by the American Gastroenterological Association 1.
- Depending on initial findings, further imaging such as CT, MRI/MRCP, or ERCP may be indicated.
- For persistent unexplained abnormalities, a liver biopsy may be necessary for definitive diagnosis, as recommended by the guidelines for detection, assessment, and management of suspected drug-induced liver injury during clinical trials in oncology patients 1. The pattern of abnormalities helps direct the workup -
- predominantly elevated transaminases suggests hepatocellular injury (viral hepatitis, drug-induced liver injury, autoimmune hepatitis),
- while elevated alkaline phosphatase and direct bilirubin suggest cholestatic or obstructive processes (gallstones, primary biliary cholangitis, malignancy) 1. Prompt evaluation is important as early intervention can prevent progression of liver disease.
- The management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy should also be considered, as outlined in the ASCO guideline update 1.
- The detection, assessment, and management of suspected drug-induced liver injury during clinical trials in oncology patients should be guided by the most recent recommendations 1.
From the Research
Transaminitis Workup
- The workup for transaminitis involves a thorough history and physical examination to identify potential causes, such as viral hepatitis, drug-induced liver injury, and autoimmune disorders 2, 3.
- Laboratory tests, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT), can help evaluate hepatocellular function and detect liver damage 3.
- Imaging studies, such as ultrasonography, may be necessary to assess the biliary tree and liver for potential causes of transaminitis 4.
Hyperbilirubinemia Workup
- The evaluation of hyperbilirubinemia starts with a careful history and physical examination to identify potential causes, such as liver disease, hemolysis, or bile duct obstruction 4, 5.
- Laboratory tests, including bilirubin levels and liver function tests, can help diagnose and manage hyperbilirubinemia 4, 5.
- Imaging studies, such as ultrasonography, may be necessary to assess the biliary tree and liver for potential causes of hyperbilirubinemia 4.
Differential Diagnosis
- The differential diagnosis for transaminitis and hyperbilirubinemia is broad and includes various liver diseases, such as viral hepatitis, nonalcoholic fatty liver disease, and alcoholic liver disease 2, 3, 6.
- Other potential causes of transaminitis and hyperbilirubinemia include drug-induced liver injury, autoimmune disorders, and extrahepatic sources, such as thyroid disorders and hemolysis 3, 6.
- A thorough workup, including laboratory tests and imaging studies, is necessary to identify the underlying cause of transaminitis and hyperbilirubinemia 2, 3, 4, 5, 6.