Drug-induced liver injury: Do we know everything?

Table 4 Classic Clinical Syndromes of drug-induced liver injury and the drugs most commonly associated[6,7,117]

Acute viral hepatitis-like: e.g., INH: Absence of hypersensitivity symptoms; present with malaise, fatigue, anorexia, nausea, vomiting, right upper quadrant pain

Hypersensitivity syndrome: Fever, rash, and/or eosinophilia seen in 25%-30% of DILI cases, usually with short latency and prompt rechallenge response (e.g., amoxicillin-clavulanate, phenytoin, carbamazepine, SMX-TMP, halothane)

Sulfone syndrome: e.g., dapsone: Fever, exfoliative dermatitis, lymphadenopathy, atypical lymphocytosis, eosinophilia, hemolytic anemia, methemoglobinemia

Pseudomononucleosis syndrome: e.g., phenytoin, dapsone, sulfonamides: Hypersensitivity syndrome with atypical lymphocytosis, lymphadenopathy, and splenomegaly

DILI associated with severe skin injury: Stevens-Johnson syndrome, toxic epidermal necrolysis, e.g., beta-lactam antibiotics, allopurinol, carbamazepine

Autoimmune hepatitis associated with positive autoantibodies: e.g., nitrofurantoin, minocycline, methyldopa

Immune-mediated colitis with autoimmune hepatitis: e.g., ipilimumab

Acute cholecystitis-like: e.g., erythromycin estolate

Reye syndrome-like: e.g., valproic acid: Hepatocellular injury, acidosis, hyperammonemia, encephalopathy, abdominal pain, nausea, vomiting, paradoxical worsening of seizure activity, microvesicular steatosis on biopsy

INH: Isoniazid; SMX: Sulfamethoxazole; TMP: Trimethoprim; DILI: Drug-induced liver injury.