Drug Safety

, Volume 32, Issue 1, pp 55–68

Drug-Induced Liver Injury Network (DILIN) Prospective Study

Rationale,Design and Conduct
  • Robert J. Fontana
  • Paul B. Watkins
  • Herbert L. Bonkovsky
  • Naga Chalasani
  • Timothy Davern
  • Jose Serrano
  • James Rochon
  • the DILIN Study Group
Original Research Article

DOI: 10.2165/00002018-200932010-00005

Cite this article as:
Fontana, R.J., Watkins, P.B., Bonkovsky, H.L. et al. Drug-Safety (2009) 32: 55. doi:10.2165/00002018-200932010-00005

Abstract

Background: Drug-induced liver injury (DILI) is an uncommon adverse drug reaction of increasing importance to the medical community, pharmaceutical industry, regulatory agencies and the general public.

Objectives: The Drug-Induced Liver Injury Network (DILIN) was established to advance understanding and research into DILI by initiating a prospective registry of patients with bona fide DILI for future studies of host clinical, genetic, environmental and immunological risk factors. The DILIN was also charged with developing standardized nomenclature, terminology and causality assessment instruments.

Methods: Five clinical sites, a data coordinating centre and senior scientists from the National Institute of Diabetes and Digestive and Kidney Diseases initiated the DILIN prospective study in September 2004. Eligible patients are required to meet minimal laboratory or histological criteria within 6 months of DILI onset and have other competing causes of liver injury excluded. Patients in the general community setting with pre-existing HIV, hepatitis B virus or hepatitis C virus infections and/or abnormal baseline liver biochemistries are eligible for enrolment. In addition, subjects with liver injury due to herbal products are eligible to participate. Control patients without DILI are also to be recruited in the future.

Results: All referred subjects undergo an extensive review of available laboratory, pathology and imaging studies. Subjects who meet pre-defined eligibility criteria at the 6-month study visit are followed for 2 years to better define the natural history of chronic DILI. Causality assessment is determined by a panel of three hepatologists who independently assign a causality score ranging from 1 (definite) to 5 (unlikely) as well as a severity score ranging from 1 (mild) to 5 (fatal). During the first 3 years, 367 subjects were enrolled into the DILIN prospective study. Conclusion: DILIN is a multicentre research network charged with improving our understanding of the aetiologies, risk factors and outcomes of DILI in the US. The network is meeting the targeted enrolment of ten patients per month and is developing a repository of clinical data and biological samples for future studies of DILI pathogenesis and outcome.

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Robert J. Fontana
    • 1
  • Paul B. Watkins
    • 2
  • Herbert L. Bonkovsky
    • 3
    • 4
    • 5
    • 6
  • Naga Chalasani
    • 7
  • Timothy Davern
    • 8
  • Jose Serrano
    • 9
  • James Rochon
    • 10
  • the DILIN Study Group
  1. 1.Department of Internal MedicineUniversity of Michigan Medical SchoolAnn ArborUSA
  2. 2.Department of Internal MedicineUniversity of North CarolinaChapel HillUSA
  3. 3.Department of Internal MedicineCenter for Liver and Digestive DiseasesCharlotteUSA
  4. 4.Department of Medicine and Cannon Research CenterCarolinas Medical CenterCharlotteUSA
  5. 5.Department of MedicineUniversity of Connecticut Health CenterFarmingtonUSA
  6. 6.Department of MedicineUniversity of North CarolinaChapel HillUSA
  7. 7.Department of Internal MedicineIndiana UniversityIndianapolisUSA
  8. 8.Department of Internal MedicineUniversity of CaliforniaSan FranciscoUSA
  9. 9.Liver Disease Research Branch, National Institutes of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA
  10. 10.Duke Clinical Research InstituteDurhamUSA
  11. 11.3912 Taubman CenterAnn ArborUSA

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