title: Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct.
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.
  
  
  OBJECTIVE
  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 enrollment. 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.
  
  
  CONCLUSIONS
  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 enrollment of ten patients per month and is developing a repository of clinical data and biological samples for future studies of DILI pathogenesis and outcome.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0362, USA. rfontana@med.umich.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.forename: Paul B
authors.initials: PB
authors.lastname: Watkins
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
authors.forename: Timothy
authors.initials: T
authors.lastname: Davern
authors.forename: Jose
authors.initials: J
authors.lastname: Serrano
authors.forename: James
authors.initials: J
authors.lastname: Rochon
mesh_terms: D056486:Chemical and Drug Induced Liver Injury; D064420:Drug-Related Side Effects and Adverse Reactions; D005500:Follow-Up Studies; D006801:Humans; D054586:National Institute of Diabetes and Digestive and Kidney Diseases (U.S.); D011446:Prospective Studies; D012042:Registries; D012107:Research Design; D012307:Risk Factors; D012720:Severity of Illness Index; D009626:Terminology as Topic; D014481:United States / Q000453:epidemiology