Drug-Induced Liver Injury

Bonkovsky, Herbert L.; Jones, Dean P.; Russo, Mark W.; Shedlofsky, Steven I.

doi:10.1016/b978-1-4377-0881-3.00025-5

Cited by 15 publications

(25 citation statements)

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“…DILI is a diagnosis of exclusion and it is both under-recognized and under-reported (Bonkovsky et al 2012). Even when the diagnosis is made, it is often difficult to ascertain which of several possible causative drugs or herbals/dietary supplements are the cause of the liver injury.…”

Section: Discussionmentioning

confidence: 99%

“…Even when the diagnosis is made, it is often difficult to ascertain which of several possible causative drugs or herbals/dietary supplements are the cause of the liver injury. This is a growing problem in the current era of polypharmacy for most patients, especially those in older age groups who are more susceptible to DILI (Bonkovsky et al 2012; DeLemos et al 2016) and in whom chronic and ongoing DILI are more likely (Fontana et al 2015). Thus, there is growing need for a simple and reliable biomarker, both to identify those with DILI and to predict likely clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Drug induced liver injury (DILI) is a growing problem that is under-recognized and under-reported (Bonkovsky et al 2012; Chalasani et al 2008, 2014, 2015). Among reasons for this are the growing numbers of drugs, herbals and dietary supplements that are consumed by billions of persons worldwide and the difficulties encountered in establishing a diagnosis of DILI (Agarwal et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Work from the Network recently showed that T cells are frequent in liver biopsies from patients with DILI (Foureau et al 2015), and that risks of DILI development are associated with certain HLA types (Lucena et al 2011; reviewed in Bonkovsky et al 2012). Therefore, some cases of idiosyncratic DILI may be mediated by hypersensitivity or allergic reactions to the drug.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, some cases of idiosyncratic DILI may be mediated by hypersensitivity or allergic reactions to the drug. These types of reactions, often referred to as immuno-allergic or allergic hepatitis, or immuno-allergic DILI, often (but not always) present with features that include laboratory findings of hepatocellular and/or cholestatic injury along with skin rash, facial edema, eosinophilia, fever, and/or lymphadenopathy (Fontana et al 2010; Bonkovsky et al 2012). The mechanism for immuno-allergic DILI reactions has been hypothesized to be mediated by drug- or drug metabolite-specific T-cells (referenced here simply as drug-specific T-cells) (Ju 2005; Tujios and Fontana 2011; Kim et al 2015).…”

Section: Introductionmentioning

confidence: 99%

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Development of a modified lymphocyte transformation test for diagnosing drug-induced liver injury associated with an adaptive immune response

Whritenour

Zong

et al. 2017

Journal of Immunotoxicology

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Drug induced liver injury (DILI) is a growing problem. Diagnostic methods to differentiate DILI caused by an adaptive immune response from liver injury of other causes or to identify the responsible drug in patients receiving multiple drugs, herbals, and/or dietary supplements (polypharmacy) have not yet been established. The lymphocyte transformation test (LTT) has been proposed as a diagnostic method to determine if a subject with an apparent hypersensitivity reaction has become sensitized to a specific drug. In this test, peripheral blood mononuclear cells (PBMC) collected from a subject are incubated with drug(s) suspected of causing the reaction. Cell proliferation, measured by the incorporation of [3H]-thymidine into new DNA, is considered evidence of a drug-specific immune response. The objectives of the current studies were to: 1) develop and optimize a modified version of the LTT (mLTT) and 2) investigate the feasibility of using the mLTT for diagnosing DILI associated with an adaptive immune response and identifying the responsible drug. PBMC collected from donors with a history of drug hypersensitivity reactions to specific drugs (manifested as skin rash) were used as positive controls for assay optimization. Following optimization, samples collected from 24 subjects enrolled in the U.S. Drug-Induced Liver Injury Network (DILIN) were tested in the mLTT. Using cytokine and granzyme B production as the primary endpoints to demonstrate lymphocyte sensitization to a specific drug, most samples from the DILIN subjects failed to respond. However, robust positive mLTT responses were observed for two of four samples from three DILIN subjects with hepatitis due to isoniazid (INH). We conclude that the mLTT, as performed here on frozen and thawed PBMC, is not a reliable test for diagnosing DILI caused by all drugs, but that it may be useful for confirming the role of the adaptive immune response in DILI ascribed to INH.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Development of a modified lymphocyte transformation test for diagnosing drug-induced liver injury associated with an adaptive immune response

Whritenour

Zong

et al. 2017

Journal of Immunotoxicology

Self Cite

View full text Add to dashboard Cite

show abstract