About the Retrospective Study

A Study of Drug-Induced Liver Injury Due to Phenytoin, Isoniazid, Amoxicillin/Clavulanic Acid, Valproic Acid, Nitrofurantoin, Trimethoprim-Sulfamethoxazole, Minocycline, and Quinolone antibiotics

Background

Drug-induced liver injury (DILI) is the most common reason for regulatory actions concerning drugs in development and in clinical practice. Fortunately, severe DILI leading to jaundice is an infrequent event, with an annual incidence ranging from 1 in 10,000 to 1 in 1,000,000 prescription-years. The idiosyncratic nature of DILI plus its low incidence have hampered our ability to identify clinical, environmental, and genetic susceptibility factors. As a result, there is a great need to improve our detection, definition, and understanding of the mechanism of DILI.

To stimulate research, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has established the Drug-Induced Liver Injury Network (DILIN) to conduct controlled, clinical studies into DILI.

ILIAD’s Research Goals

  • Establish a database of patients with severe DILI due to any of 7 specific drugs and one drug class.
  • Establish a bank of biological specimens (serum, DNA, and immortalized lymphocytes) from DILI cases and controls.
  • Maintain a registry of DILI cases with annual contact.

How You Can Help

We need your help with patient recruitment. If you have patients who are eligible, contact the DILIN clinical site closest to you.

Eligibility Criteria

  • Alive, with DILI onset on or after January 1, 1994.
  • Age > 2 years old at enrollment.
  • The implicated medications are isoniazid (INH), phenytoin (Dilantin), combination clavulanic acid / amoxicillin (Augmentin), valproic acid (Depakote), nitrofurantoin, trimethoprim-sulfamethoxazole, minocycline, and quinolone antibiotics
  • Peak total serum bilirubin > 2.5 mg/dl or, if valproic acid, INR > 1.5 / hospitalized.
  • Detailed documentation of the event for causality assessment.

Study Protocol

  • Screening criteria are reviewed during the initial contact with the subject.
  • Clinical data are collected using a telephone or personal-interview format.
  • Detailed data are abstracted from medical records and charts.
  • A blood sample is drawn and forwarded to a repository.

To contact the DILIN clinical site closest to you…