Drug induced liver injury must be differentiated from other diseases that cause serum transaminase elevations and symptoms of acute liver injury^[1]:

The following diseases are in the differential of drug induced liver injury:

• Acute viral hepatitis
• Alcoholic liver disease
• Autoimmune hepatitis
• Budd-Chiari syndrome
• Cholangitis
• Cholecystitis
• Cholestatic liver disease
• Coagulation disorders
• Hemochromatosis
• Malignancy
• Pregnancy-related conditions of liver
• Shock liver
• Wilson disease

Some medications (e.g. minocycline, nitrofurantoin) cause autoimmune-like drug induced liver injury, which must be distinguished from autoimmune hepatitis using serum studies such as antinuclear antibody, immunoglobulin G, and anti-smooth muscle antibody.

In patients below the age of forty, it is important to rule out Wilson’s Disease, though rare, with serum ceruloplasmin. However, ceruloplasmin may also be falsely normal or even elevated as an acute-phase reactant during episodes of acute hepatitis. Further testing if indicated would include slit lamp examination and 24-hour urine copper collection.

If tender hepatomegaly and ascites are present, ultrasound with doppler should be obtained to assess for Budd-Chiari syndrome.

Other etiologies that may have overlapping presentations with cholestatic liver injury include:

• Extrahepatic etiologies:
  • Choledocholithiasis
  • Malignancy (e.g. lymphoma)
• Intrahepatic etiologies
  • Primary biliary cirrhosis
  • Primary sclerosing cholangitis