Drug-Induced Liver Injury (DILN)Network Retrospective (ILIAD)

Patients with liver injury ascribed to isoniazid, phenytoin, clavulanic acid/amoxicillin, valproic acid, nitrofurantoin, trimethoprim-sulfamethoxazole, minocycline, and quinolone antibiotics

Inclusion Criteria:

Screening Criteria

To be included in the ILIAD registry, the following criteria must be satisfied:

• The treating gastroenterologist / hepatologist or health care professional must believe that the subject suffered drug-induced liver injury;
• The subject must be alive and the date of onset of the qualifying DILI episode must have occurred on or after January 1, 1994;
• The implicated medication is one of the following: isoniazid, phenytoin, combination clavulanic acid / amoxicillin,valproic acid, nitrofurantoin, trimethoprim-sulfamethoxazole, minocycline, and quinolone antibiotics;
• The subject is taking only one of these medications in the period leading up to the onset of the qualifying DILI episode;
• For INH, phenytoin, clavulanic acid / amoxicillin, trimethoprim-sulfamethoxazole, or quinolone antibiotics, total serum bilirubin > 2.5 mg/dL;
• For nitrofurantoin or minocycline, total serum bilirubin > 2.5 mg/dL or documented fibrosis/cirrhosis on liver biopsy;

• For valproic acid, compatible symptomatic clinical presentation that is severe enough to prompt hospitalization, or that is associated with significant biochemical liver dysfunction, defined as any of the following:

  1. INR > 1.5
  2. Serum AST or ALT > 3 x the baseline level, if the baseline level is elevated.
  3. Bilirubin >1 x ULN or > 1 x the baseline level, if the baseline level is elevated
  4. Unexplained elevated arterial or venous NH3 levels
  5. Liver biopsy showing steatosis
• Sufficient documentation of the event for the Causality Committee to make a determination.

Exclusion Criteria:

Subjects will be excluded according to the following criteria:

• are not willing to have medical information and blood samples taken;
• are unable to adequately give informed consent to participate in the study including the blood draw for the genetic component;
• age < 2 years old at the time of study enrollment (due to blood volume requirements).
• are diagnosed with a specific seizure syndrome associated with known genetic defects if the implicated drug is valproate or phenytoin.