DILIN's Prospective Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT00345930
Recruitment Status : Recruiting
First Posted : June 29, 2006
Last Update Posted : April 19, 2018
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Duke University

June 27, 2006
June 29, 2006
April 19, 2018
September 2004
July 2022   (Final data collection date for primary outcome measure)
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Complete list of historical versions of study NCT00345930 on Archive Site
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DILIN's Prospective Study
A Multi-Center, Longitudinal Study of Drug-and CAM-Induced Liver Injury
The purpose of this study is to identify individuals who have suffered a liver injury arising as an idiosyncratic reaction to a prescription drug or a complementary and alternative medicine. Recently added acute cases enrollment that meets criteria to the protocol. Also added Fibroscans to the protocol that will be completed at baseline and follow-up on chronic subjects.

Liver injury due to prescription and non-prescription medication use is a medical, scientific and public health problem of increasing frequency and importance in the United States. Indeed, drug-induced liver injury (DILI) is the most important reason for non-approval, withdrawal, limitation in use and clinical monitoring by the Food and Drug Administration (FDA). However, detection of signals for liver injury frequently relies upon the reporting of cases by practitioners to health authorities in post-marketing surveillance. Under-reporting of cases, lack of mandatory reporting systems, and difficulties in establishing a diagnosis make the current system sub-optimal. Moreover, with the growing use of complementary and alternative medications (CAM), there have also been increasing reports of liver toxicity due to various non-prescription herbal, dietary and food additive supplements. Because the manufacturing, dispensing and testing of these products is not regulated, the hepatotoxic potential of these formulations is poorly characterized or completely unknown.

The DILIN Prospective Study is a multi-centered epidemiological study designed to gather clinical information and biological specimens on cases of suspected liver injury due to drugs and CAM. 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.

Patients who are referred to one of the DILIN clinical sites and who, in the opinion of gastroenterologist/hepatologist, experienced a drug-induced liver injury are enrolled. Detailed clinical data and biological specimens are collected. Clinical data will be reviewed by the DILIN Causality Committee and the final determination on whether the subject qualifies as a bona fide DILI case is made by consensus opinion. DILI cases (only) are followed for at least 6 months to derive the longitudinal profile of drug-and CAM-induced liver injury. Detailed clinical data including liver elastography (FibroScans) and biological specimens are collected. Patients who satisfy the definition of chronic DILI will be evaluated with additional FibroScans at 12, 24, 36 and 48 months thereafter.

Observational Model: Case-Control
Time Perspective: Prospective
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Retention:   Samples With DNA
Samples with DNA
Non-Probability Sample
Patients who have suffered a drug induced liver injury and meet inclusion and exclusion criteria
Liver Diseases
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  • 2
    Individuals without drug induced liver disease
  • 1
    Individuals with drug induced liver disease

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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July 2022
July 2022   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age > 2 years at enrollment into the study.
  • 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 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 Criteria:

Patients with any of the following will not be eligible for participation:

  • Competing cause of acute liver injury such as hepatic ischemia that is felt by the investigator to be the primary reason for observed liver injury and supported by laboratory tests, serologies, liver biopsy, or radiology.
  • Known, pre-existing autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, or other chronic biliary tract disease which may confound the ability to make a diagnosis of DILI.
  • Acetaminophen hepatotoxicity.
  • Liver/bone marrow transplant prior to the development of drug- or CAM-induced liver injury.
Sexes Eligible for Study: All
2 Years and older   (Child, Adult, Senior)
Contact: Katherine Galan, RN 919-668-8579
Contact: Theresa O'Rielly 919-668-8465 theresa.o'
United States
5U01DK065176-11 ( U.S. NIH Grant/Contract )
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Duke University
Duke University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Huiman X. Barnhart, PhD Duke University
Study Chair: Paul Watkins, MD University of North Carolina, Chapel Hill
Duke University
April 2018