Table 3.

Common causes of severe liver injury

Category	Common examples	Additional investigations
Drug-induced hepatitis	Dose-dependent Idiosyncratic	Medication history, rule out other possible causes, CBC, liver biopsy
Viral hepatitis	Hepatitis A, B, C, D, and E Epstein–Barr (EBV) virus Cytomegalovirus (CMV) Human immunodeficiency virus (HIV), HSV, Parvovirus B19	Drug and travel history, hepatitis A IgM, hepatitis B surface antigen (HBsAg), anti-HBc, anti-HBs, anti-HCV, anti-HBc-IgM, HBeAg, monotest, EBV serology, EBV DNA by PCR, CMV serology, CMV DNA by PCR, HIV antibody
Alcoholic hepatitis	Ethanol ingestion	Serum ethanol level, AST to ALT ratio (2:1 or greater may suggest ethanol injury)
Toxic hepatitis	Vinyl chloride Pyrrolizidine alkaloids (i.e. found in certain teas) Poisonous mushrooms	Diet history, vinyl chloride breath test or urine test for thiodiglycolic acid
Autoimmune hepatitis	Overlap autoimmune hepatitis Type 1 autoimmune hepatitis Type 2 autoimmune hepatitis	In general, consider: total IgG, gamma-globulin level, anti-soluble liver antigen or liver pancreas (anti-SLA/LP) antibody, liver biopsy Anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-actin antibody (AAA), anti-dsDNA antibody, anti-soluble liver antigens (SLA) antibody, anti-neutrophil cytoplasmic antibody (ANCA), anti-mitochondrial antibody (AMA) Anti-liver kidney microsomal 1 (anti-LKM1) antibody, anti-liver cytosol antigen (anti-LC1), atypical p-ANCA (pANNA), anti-soluble liver antigens (SLA)
Ischemic hepatitis	Budd-Chiari syndrome (hepatic vein obstruction) Shock	CBC, lactate, hypercoagulopathy workup, age-appropriate malignancy workup, abdominal ultrasound, CT, or MRI

The above are causes of liver injury that can result in liver enzyme elevations that exceed 1000 U/L, or 25 times the upper limit of normal