Drug-Induced Liver Injury Network (DILIN)A Multi-Center, Longitudinal Study of Drug- and CAM-Induced Liver Injury
The primary objective of this study is to prospectively identify bona fide cases of liver injury due to drugs and complementary and alternative medications within 6 months of the date of onset of the liver injury. Secondary objectives include collecting clinical data and biological specimens including blood, DNA, urine, and liver tissue from affected patients for future mechanistic and genetic studies of DILI. The natural history of drug- and CAM-induced DILI will be tracked for at least 6 months following enrollment, with longer follow-up for those in whom there is evidence of chronic liver injury at 6 months. We will also develop and test causality assessment instruments for drug and CAM-induced liver injury that are sensitive, specific, and reproducible.
Consecutive patients who are referred to one of the DILIN clinical sites and appear to have suffered a drug-Induced liver injury will be considered for inclusion in the study. Subjects must be ≥2 years at the time of enrollment; have evidence of liver injury that is known or suspected to be related to con-sumption of a drug or CAM product in the 6-month period prior to enrollment; and, have documented clinically important DILI defined in terms of serum aspartate aminotransferase (AST), alanine amino-transferase (ALT), and alkaline phosphatase (Alk Phos) as described below. Subjects will be excluded if there is acetaminophen hepatotoxicity, a competing cause of acute liver injury, or liver transplant prior to the development of drug- or CAM-induced liver injury.
• Age >2 years at 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.
• Written Informed consent from the patient or the patient’s legal guardian.
• Documented clinically important DILI, defined as any of the following:
1. ALT or AST >5 x ULN or A P’ase >2 x ULN observed 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
3. Any elevation of ALT, A P’ase, or AST, associated with (a) increased total bilirubin [ ≥ 2.5
mg/dL], in the 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