Drug-Induced Liver Injury Network (DILIN) Prospective Study

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.

Drug and herb induced liver injury: Council for International Organizations of Medical Sciences scale for causality assessment

“…For clinicians, the TTK scale cannot replace the CIOMS scale [25] . The DILIN method provided by the DILIN group requires an expert panel [3,6,11,24,44,45,49,50,77,78] , in contrast to the CIOMS scale [21,24] . Consequently, the DILIN method is of limited availability to physicians in need of early results for therapeutic decisions [24] .…”

“…This includes the novel Causality Assessnovel Causality Assessment Tool (CAT) specifically designed for herbs and dietary supplements (HDS), which was presented as an abstract [15] . As opposed to CIOMS based results with transparent data presentation (Table 7) [12,30,32,[36][37][38][39]47,48,71] , publications based on the DILIN method lack transparency for individual cases regarding assessed and scored items since only final causality levels are published without details and thereby open for discussions, not allowing valid conclusions [3,6,11,49,50,77,78] . The DILIN method also lacks data on specificity, sensitivity and predictive values, as an expert opinion based method no items can be validated.…”

Update on Advances in Research on Idiosyncratic Drug-Induced Liver Injury

“…To overcome these limitations, international multicenter research networks have been established in accordance with case definition and phenotype standardization as well as with regard to grading the severity of DILI. 13 Multicenter research networks for studying idiosyncratic DILI have been established in the USA (DILIN), 14 UK (DILIGEN), 10 Europe (EUDRAGENE), 15 Spain (Spain DILI registry), 16 Canada (CPNDS), 17 and the international Severe Adverse Event consortium (SAE). 18 An association between a specific human leukocyte antigen (HLA) allele with idiosyncratic DILI has been reported for several drugs (e.g., flucloxacillin [B ).…”

Cellular and Molecular Aspects of Drug-Induced Liver Toxicity: Recent Prominent Mechanisms

“…In United States, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has established the Drug-Induced Liver Injury Network (DILIN) to collect and analyze cases of severe liver injury induced by prescribed drugs, over-the-counter (OTC) drugs, and alternative medicines, such as herbal products and dietary supplements [48]. Besides, The National Institutes of Health (NIH) has created a database named "LIVERTOX" for drugs that may lead to the development of DILI.…”