Epidemiology and Management of Drug-induced Liver Injury: Importance of the Updated RUCAM

Kobayashi, Takashi; Iwaki, Michihiro; Nogami, Atsushi; Yoneda, Masato

doi:10.14218/jcth.2022.00067s

Cited by 5 publications

(10 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All data above were derived from iDILI cases assessed for causality using either the original RUCAM [17,18] or the updated RUCAM [19]. On top of the list are reports presenting preferentially individual drugs [35,59,74,77,80,81,83,[87][88][89][90] whereas in the lower part of the list, the reports contain drug classes [83,84,[91][92][93][94][95][96][97]. Abbreviations: INH-RIP-PIZ, Isoniazid-Rifampicin-Pyrazinamide; NSAIDs, nonsteroidal anti-inflammatory drugs.…”

Section: Immunosuppressantsmentioning

confidence: 99%

Idiosyncratic DILI and RUCAM under One Hat: The Global View

Teschke,

Danan

2023

Livers

View full text Add to dashboard Cite

Drugs are prescribed worldwide to treat diseases but with the risk of idiosyncratic drug-induced liver injury (iDILI). The most important difficulty is how best to establish causality. Based on strong evidence and principles of artificial intelligence (AI) to solve complex processes through quantitative algorithms using scored elements, progress was achieved with the Roussel Uclaf Causality Assessment Method (RUCAM) in its original and updated versions, often viewed now as the gold standard. As a highly appreciated diagnostic algorithm, the RUCAM is in global use with around 100,000 iDILI cases published worldwide using RUCAM to assess causality, largely outperforming any other specific causality assessment tool in terms of case numbers. Consequently, the RUCAM helps to establish a list of top-ranking drugs worldwide implicated in iDILI and to describe clinical and mechanistic features of iDILI caused by various drugs. In addition, the RUCAM was recently applied in iDILI cases of patients treated for coronavirus disease 2019 (COVID-19) infections or cancer patients treated with immune checkpoint inhibitors (ICIs), as well as in the search for new treatment options with conventional drugs in iDILI. Analyses of RUCAM-based iDILI cases are helpful to support pathogenetic steps like immune reactions, genetic predisposition as evidenced by human leucocyte antigens (HLA) genotypes for selected drugs, and the role of the gut microbiome. To achieve consistency in data collection, analysis, and specific clinical and pathogenetic presentation, researchers, regulatory agencies, and pharmaceutical firms should place iDILI and the updated RUCAM as the causality tool under one and the same hat in review articles and clinical guidelines for the diagnosis and treatment of iDILI.

show abstract

Section: Immunosuppressantsmentioning

confidence: 99%

Idiosyncratic DILI and RUCAM under One Hat: The Global View

Teschke,

Danan

2023

Livers

View full text Add to dashboard Cite

show abstract

“…As APAP has limitations that include a narrow therapeutic window and adverse effects, new, effective approaches and studies of the mechanisms of DILI are urgently required. 4 , 5 …”

Section: Introductionmentioning

confidence: 99%

“…As APAP has limitations that include a narrow therapeutic window and adverse effects, new, effective approaches and studies of the mechanisms of DILI are urgently required. 4,5 APAP-induced liver injury (AILI) is the predominant cause of DILI, and several studies have been conducted to explore its fundamental mechanisms. [6][7][8] Excessive oxidative stress leads to mitochondrial dysfunction and c-Jun N-terminal kinase (JNK) overactivation, which is considered to be the major cause of APAP-induced cell death.…”

Section: Introductionmentioning

confidence: 99%

BTF3L4 Overexpression Mediates APAP-induced Liver Injury in Mouse and Cellular Models

Lin,

Fan,

Yifu

et al. 2024

J Clin Transl Hepatol

View full text Add to dashboard Cite

Background and Aims Acetaminophen (APAP)-induced liver injury (AILI) has an increasing incidence worldwide. However, the mechanisms contributing to such liver injury are largely unknown and no targeted therapy is currently available. The study aimed to investigate the effect of BTF3L4 overexpression on apoptosis and inflammation regulation in vitro and in vivo . Methods We performed a proteomic analysis of the AILI model and found basic transcription factor 3 like 4 (BTF3L4) was the only outlier transcription factor overexpressed in the AILI model in mice. BTF3L4 overexpression increased the degree of liver injury in the AILI model. Results BTF3L4 exerts its pathogenic effect by inducing an inflammatory response and damaging mitochondrial function. Increased BTF3L4 expression increases the degree of apoptosis, reactive oxygen species generation, and oxidative stress, which induces cell death and liver injury. The damage of mitochondrial function by BTF3L4 triggers a cascade of events, including reactive oxygen species accumulation and oxidative stress. According to the available AILI data, BTF3L4 expression is positively associated with inflammation and may be a potential biomarker of AILI. Conclusions Our results suggest that BTF3L4 is a pathogenic factor in AILI and may be a potential diagnostic maker for AILI.

show abstract

“…Idiosyncratic drug induced liver injury (iDILI) by multiple drugs and drug classes is a complex disease [1][2][3][4], carefully discussed under the aspects of causality assessment using the Roussel Uclaf Causality Assessment Method (RUCAM) as its original of1993 [5,6] or its updated version of 2016 [7]. Similarly, the updated RUCAM was applied in iDILI cases due to rosuvastatin [8], tyrosine-kinase inhibitors [9], teriflunomide [10], tigecycline [11], potassium para aminobenzoate [12], androgenic anabolic steroids [13], atezolizumab [14], durvalumab [15], memantine [16], with several drugs in the elderly [17], in newborns and children [18], and in a Brazil hospital pharmacy setting [19].…”

Section: Introductionmentioning

confidence: 99%

“…In some of the RUCAM related reports [1][2][3][4][8][9][10][11][12][13][14][15][16][17][18][19], the issue of specific human leucocyte antigens (HLA) allele variability was mentioned, which are under discussion being involved as genetic factors in causing the liver injury. In addition, immune mechanisms may play a role in iDILI, but proposals were mainly based on narratives rather than on iDILI cases with established causality assessment like RUCAM [5][6][7], which helps find and exclude alternative commonly found among published cohorts of patients with iDILI [7].…”

Section: Introductionmentioning

confidence: 99%

Idiosyncratic DILI: Immunology in Cases with Evidence Based on RUCAM

Teschke

2023

J. Mod. Med. Chem.

View full text Add to dashboard Cite

Idiosyncratic drug induced liver injury (iDILI) is a multifaceted and fairly well described liver disease, but there is yet some uncertainty on the role of immune systems triggering the liver injury and speculation on the cascade of immune events. Many conclusions were so far based on narratives or cases of iDILI, which did not receive the benefit of a robust causality assessment like by the Roussel Uclaf Causality Assessment Method (RUCAM). This analysis aims to clarify the cascade of immune events that lead to the liver injury by conventional drugs. For this approach, the search focused on iDILI cases with verified diagnosis by RUCAM. Most promising were parameters obtained from the blood as mirror of what happened in the liver during the injurious processes.The focus of this present analysis is on patients with RUCAM based iDILI and concomitant immune-related parameters in the blood. As an example, compelling evidence for a role of immune systems in iDILI was found for circulating mediators in the blood secreted by liver immune cells in patients under a therapy for tuberculosis, detected were also serum anti-cytochrome P450 (CYP) antibodies in patients after anesthesia with sevoflurane or desflurane and thereby reflecting their metabolism by the CYP 2E1 isoform, the occurrence of serum of autoantibodies in patients with drug induced autoimmune hepatitis (DIAIH) due to many drugs, and the role of blood and liver monocytes, which provide direct evidence for the activation of the hepatic innate immune system to the adapted immune system. In essence, patients with RUCAM based iDILI show various immunology features in the blood compatible with the role of the hepatic immune systems in patients with suspected iDILI caused by some but not all drugs.

show abstract

Epidemiology and Management of Drug-induced Liver Injury: Importance of the Updated RUCAM

Cited by 5 publications

References 54 publications

Idiosyncratic DILI and RUCAM under One Hat: The Global View

Idiosyncratic DILI and RUCAM under One Hat: The Global View

BTF3L4 Overexpression Mediates APAP-induced Liver Injury in Mouse and Cellular Models

Idiosyncratic DILI: Immunology in Cases with Evidence Based on RUCAM

Contact Info

Product

Resources

About