Drug‐induced liver injury associated with severe cutaneous adverse drug reactions: A nationwide study in Taiwan

Abstract Background Drug-induced liver injury (DILI) represents an increasing morbidity in the general population, but more so in the elderly cohort of patients. Despite this, the concept of its prevention through prospective analysis has largely remained unexamined. We evaluated the utility of recently validated adverse drug reactions (ADR) avoidability tool in a cohort of elderly patients with DILI. Methods We examined 38 DILI-drug pairs from n=38 patients in a prospective cohort of patients presenting with adverse drug reactions to a Weill Cornell-affiliated tertiary hospital between February 2019 and January 2020. DILI outcomes were adjudicated by the updated Roussel Uclaf Causality Assessment Method (RUCAM). Two clinical pharmacologists and two general physicians utilized the Liverpool adverse drug reactions avoidability tool (LAAT) and the modified Hallas tools to rate the preventability of DILI-drug pairs. Inter-rater, exact agreement proportions, as well as intraclass correlation coefficients were generated and expressed as ordinal outcomes. Results The cases examined for the determination of DILI avoidability had probability likelihood of “probable” or “highly probable” by the updated RUCAM scale. Examination of the 38 DILI-drug pairs (n= 38 patients) resulted in a total of 152 ordinal outcome decisions. We found about 32.3% (50/152) and 34.2% (52/152) of DILI-drug pairs were rated as “avoidable” (“probable” or “definite”) by the LAAT and the modified Hallas tools respectively. The overall median Krippendorf’s kappa with the LAAT was 0.61 (SE 0.12, CI 0.36, 0.85) and for modified Hallas tool was 0.53 (SE 0.18; CI 0.16, 0.89). The inter-rater correlation coefficient (ICC) for the LAAT and modified Hallas were 0.50 [0.32, 0.65] and 0.63 [0.48, 0.76] respectively. Exact pairwise agreement was present in 30/38 (IQR 29.5, 34.5), and 28/38 (IQR 27.5-35.5) of DILI-ADR pairs using the LAAT and modified Hallas tools respectively. Conclusion We found a significant proportion of drug-induced liver injury adjudicated by the updated RUCAM scale in elderly hospitalized cohort of patients were avoidable with significant implication for therapeutic commissioning as well as cost effectiveness interventions in this cohort of patients.

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Piperacillin/tazobactam induced toxic epidermal necrolysis and drug induced liver injury

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20181091 ◽

2018 ◽

Vol 5 (2) ◽

pp. 460

Author(s):

Hardeep S. Deep ◽

Mohit Kumar ◽

Barjinder Pal Singh ◽

Nisha Kajla

Keyword(s):

Drug Reaction ◽

Case Report ◽

Liver Injury ◽

Toxic Epidermal Necrolysis ◽

Adverse Drug Reactions ◽

Drug Reactions ◽

Drug Induced ◽

Biochemical Characteristics ◽

Drug Induced Liver Injury ◽

Ultimate Outcome

The liver and skin are the organs most commonly involved in serious adverse drug reactions. Rarely a drug reaction can affect both organs concurrently. The association of drug induced liver injury (DILI) and toxic epidermal necrolysis (TEN) is even rarer and may be rarely reported. This is a case report on development of both TEN and DILI following use of piperacillin / tazobactam. We describe our experience of DILI occurring in association with TEN including the etiological agent responsible, its clinical/ biochemical characteristics and ultimate outcome.

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Causality Assessment and Examples of Adverse Drug Reactions (Drug-Induced Liver Injury, Renal, Skin, and Major Adverse Cardiac Events)

Pharmacovigilance: A Practical Approach ◽

10.1016/b978-0-323-58116-5.00004-3 ◽

2019 ◽

pp. 47-67

Author(s):

Charles Schubert ◽

Monali Desai ◽

Meenal Patwardhan ◽

Fabio Lievano ◽

Syed S. Islam ◽

...

Keyword(s):

Liver Injury ◽

Adverse Drug Reactions ◽

Causality Assessment ◽

Major Adverse Cardiac Events ◽

Drug Reactions ◽

Cardiac Events ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Adverse Cardiac Events

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Performance of preclinical models in predicting drug-induced liver injury in humans: a systematic review

Scientific Reports ◽

10.1038/s41598-021-85708-2 ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Hubert Dirven ◽

Gunn E. Vist ◽

Sricharan Bandhakavi ◽

Jyotsna Mehta ◽

Seneca E. Fitch ◽

...

Keyword(s):

Liver Injury ◽

Adverse Events ◽

Adverse Drug Reactions ◽

Evidence Based ◽

Drug Reactions ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Vitro Data ◽

In Vitro Data

AbstractDrug-induced liver injury (DILI) causes one in three market withdrawals due to adverse drug reactions, causing preventable human suffering and massive financial loss. We applied evidence-based methods to investigate the role of preclinical studies in predicting human DILI using two anti-diabetic drugs from the same class, but with different toxicological profiles: troglitazone (withdrawn from US market due to DILI) and rosiglitazone (remains on US market). Evidence Stream 1: A systematic literature review of in vivo studies on rosiglitazone or troglitazone was conducted (PROSPERO registration CRD42018112353). Evidence Stream 2: in vitro data on troglitazone and rosiglitazone were retrieved from the US EPA ToxCast database. Evidence Stream 3: troglitazone- and rosiglitazone-related DILI cases were retrieved from WHO Vigibase. All three evidence stream analyses were conducted according to evidence-based methodologies and performed according to pre-registered protocols. Evidence Stream 1: 9288 references were identified, with 42 studies included in analysis. No reported biomarker for either drug indicated a strong hazard signal in either preclinical animal or human studies. All included studies had substantial limitations, resulting in “low” or “very low” certainty in findings. Evidence Stream 2: Troglitazone was active in twice as many in vitro assays (129) as rosiglitazone (60), indicating a strong signal for more off-target effects. Evidence Stream 3: We observed a fivefold difference in both all adverse events and liver-related adverse events reported, and an eightfold difference in fatalities for troglitazone, compared to rosiglitazone. In summary, published animal and human trials failed to predict troglitazone’s potential to cause severe liver injury in a wider patient population, while in vitro data showed marked differences in the two drugs’ off-target activities, offering a new paradigm for reducing drug attrition in late development and in the market. This investigation concludes that death and disability due to adverse drug reactions may be prevented if mechanistic information is deployed at early stages of drug development by pharmaceutical companies and is considered by regulators as a part of regulatory submissions.

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Faculty Opinions recommendation of A prospective nationwide study of drug-induced liver injury in Korea.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717964983.793466146 ◽

2012 ◽

Author(s):

Deirdre Kelly ◽

Way Lee Seah

Keyword(s):

Liver Injury ◽

Drug Induced ◽

Nationwide Study ◽

Drug Induced Liver Injury

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Drug-Induced Autoimmune Hepatitis following Treatment with Zoledronic Acid

Case Reports in Gastroenterology ◽

10.1159/000479314 ◽

2017 ◽

Vol 11 (2) ◽

pp. 440-445 ◽

Cited By ~ 4

Author(s):

Jenny Sarah Schneider ◽

Matteo Montani ◽

Felix Stickel

Keyword(s):

Liver Disease ◽

Zoledronic Acid ◽

Side Effects ◽

Liver Injury ◽

Drug Reactions ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

First Case ◽

Alternative Drugs

Adverse drug reactions are among the most frequent side effects of synthetic and complementary alternative drugs and represent the premier causes of license revocations and acute liver failure. Drug-induced liver injury can resemble literally any other genuine liver disease and usually responds well to drug dechallenge. However, in some cases autoimmune-like hepatitis can evolve, requiring short- and sometimes long-term immunosuppression. Here, we present the hitherto first case of autoimmune-like hepatitis following treatment with zoledronic acid.

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Drug-Induced Liver Injury

10.2310/gastro.5493 ◽

2015 ◽

Author(s):

Thanh Tran ◽

William M. Lee

Keyword(s):

Liver Injury ◽

Prescription Drugs ◽

Clinical Manifestations ◽

The United States ◽

Idiosyncratic Drug Reactions ◽

Drug Reactions ◽

Drug Induced ◽

Common Cause ◽

Drug Induced Liver Injury ◽

Study Results

Drug-induced liver injury (DILI) refers to liver damage caused by over-the-counter and prescription drugs as well as herbal and dietary supplements. Hepatocytes, the main factory cells of the liver, are the primary targets of drug-related injury. During hepatocyte injury, loss of cell integrity results in a leak of liver contents, including a variety of enzymes, into the circulation. Currently, more than 1,000 drugs and herbal products have recognized hepatotoxic properties, with acetaminophen (APAP) being the most common cause of acute liver failure in the United States and amoxicillin-clavulanate the most common cause of severe liver injury worldwide. This review of DILI addresses the epidemiology, classification, pathophysiology, clinical manifestations, diagnosis, common idiosyncratic drug reactions, unusual drug reactions, treatment, and prognosis, with special sections on APAP hepatotoxicity and the approval of prescription drugs by the Food and Drug Administration. Figures show histologic features of DILI, mechanisms of liver injury, genome-wide association study results for lumiracoxib, APAP metabolism, and the Rumack-Matthew nomogram. Tables list classification of DILI, features of idiosyncratic drug reactions, histologic patterns of DILI, haplotypes associated with specific drug-related disorders, and the Roussel-Uclaf causality assessment method. This review contains 5 highly rendered figures, 5 tables, and 54 references.

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