DILIN: Prospective (DILIN Pro)

General Description

The Drug-Induced Liver Injury Network (DILIN) was established in 2003 as a cooperative agreement among the National Institutes of Health, 5 academic clinical centers, and a data coordinating center. A major emphasis of DILIN has been to establish a protocol for the identification and enrollment of patients with clinically significant DILI into a prospective observational study and to create a registry and specimen repository of biological samples that could be used for mechanistic studies on the etiology and prevention of DILI.

The DILIN prospective study is an ongoing multicenter observational study. Patients (2 years of age or older) were enrolled in this study if there was a strong clinical suspicion that a liver injury event was caused by a medication or an herbal agent occurring within 6 months before enrollment. Additionally, patients must meet one of the biochemical criteria for enrollment into this study.

Data from the DILIN Prospective study through 2013 are available from the Repository.

Objectives

The goals of this study are to develop a database of recent DILI cases, identify the clinical, environmental and genetic risk factors that predict DILI, develop standardized instruments and terminology and perform careful longitudinal follow-up of DILI subjects. Biological samples collected will be used in future studies of the mechanisms and genetics of DILI.

Criteria

• Age > 2 years at time of enrollment
• Evidence of liver injury that is known or suspected to be related to consumption of a drug or CAM product in the 6-month period prior to enrollment.
• Documented clinically important DILI, defined as any of the following:
  1. ALT or AST >5 x ULN or A P’ase >2 x ULN confirmed on at least 2 consecutive blood draws in patients with previously normal values
  2. If baseline (BL) ALT, AST or A P’ase are known to be elevated, then ALT or AST > 5 x BL or A P’ase > 2 x BL on at least 2 consecutive blood draws. “Baseline” is defined as the average of at least 2 measurements performed during the 12-month period prior to starting the DILI medication.
  3. Any elevation of ALT, A P’ase, or AST, associated with (a) increased total bilirubin (≥ 2.5 mg/dL), in absence of prior diagnosis of liver disease, Gilbert’s syndrome, or evidence of hemolysis or (b) coagulopathy with INR > 1.5 in absence of Coumadin therapy or known vitamin K deficiency
• Exclusion: competing cause of acute liver injury, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, other chronic biliary tract diseases, acetaminophen hepatotoxicity, liver/bone marrow transplant prior to the development of drug or CAM induced liver injury