Editorial: chronic <scp>DILI</scp> and <scp>HILI</scp> – corticosteroid plus glycyrrhizin as standard therapy?

Teschke, Rolf; Eickhoff, Axel

doi:10.1111/apt.16943

Cited by 3 publications

(7 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GC treatment of patients with DILI is by no means supported by evidence because robust data derived from RCTs were not available [114]. Despite these uncertainties, GCs have empirically been used in unselected DILI cases due to various drugs [92,114,[153][154][155][156]. In addition, therapy studies using GCs have provided controversial results, and consensus exists that a validated standard GC therapy for all DILI cases does not exist [92,153,154].…”

Section: Dili By Common Drugsmentioning

confidence: 99%

“…The therapeutic efficiency of GCs was classified as good with an improvement in laboratory data and liver histology and even better results when combined with glycyrrhizin, with no death or liver transplantation reported [155]. With regrets, the study had limitations due to the randomized open-label trial study design [155,156], an avoidable shortcoming easily preventable if a prospective RCT study design is used in an upcoming study. Thus, GCs should be carefully evaluated before application and used with great caution in DILI [156].…”

Section: Dili By Common Drugsmentioning

confidence: 99%

“…With regrets, the study had limitations due to the randomized open-label trial study design [155,156], an avoidable shortcoming easily preventable if a prospective RCT study design is used in an upcoming study. Thus, GCs should be carefully evaluated before application and used with great caution in DILI [156].…”

Section: Dili By Common Drugsmentioning

confidence: 99%

See 2 more Smart Citations

Treatment of Drug-Induced Liver Injury

Teschke

2022

Biomedicines

Self Cite

View full text Add to dashboard Cite

Current pharmacotherapy options of drug-induced liver injury (DILI) remain under discussion and are now evaluated in this analysis. Needless to say, the use of the offending drug must be stopped as soon as DILI is suspected. Normal dosed drugs may cause idiosyncratic DILI, and drugs taken in overdose commonly lead to intrinsic DILI. Empirically used but not substantiated regarding efficiency by randomized controlled trials (RCTs) is the intravenous antidote treatment with N-acetylcysteine (NAC) in patients with intrinsic DILI by N-acetyl-p-aminophenol (APAP) overdose. Good data recommending pharmacotherapy in idiosyncratic DILI caused by hundreds of different drugs are lacking. Indeed, a recent analysis revealed that just eight RCTs have been published, and in only two out of eight trials were DILI cases evaluated for causality by the worldwide used Roussel Uclaf Causality Assessment Method (RUCAM), representing overall a significant methodology flaw, as results of DILI RCTs lacking RUCAM are misleading since many DILI cases are known to be attributable erroneously to nondrug alternative causes. In line with these major shortcomings and mostly based on anecdotal reports, glucocorticoids (GCs) and other immuno-suppressants may be given empirically in carefully selected patients with idiosyncratic DILI exhibiting autoimmune features or caused by immune checkpoint inhibitors (ICIs), while some patients with cholestatic DILI may benefit from ursodeoxycholic acid use; in other patients with drug-induced hepatic sinusoidal obstruction syndrome (HSOS) and coagulopathy risks, the indication for anticoagulants should be considered. In view of many other mechanistic factors such as the hepatic microsomal cytochrome P450 with a generation of reactive oxygen species (ROS), ferroptosis with toxicity of intracellular iron, and modification of the gut microbiome, additional therapy options may be available in the future. In summation, stopping the offending drug is still the first line of therapy for most instances of acute DILI, while various therapies are applied empirically and not based on good data from RCTs awaiting further trials using the updated RUCAM that asks for strict exclusion and inclusion details like liver injury criteria and provides valid causality rankings of probable and highly probable grades.

show abstract

Section: Dili By Common Drugsmentioning

confidence: 99%

Section: Dili By Common Drugsmentioning

confidence: 99%

See 1 more Smart Citation

Treatment of Drug-Induced Liver Injury

Teschke

2022

Biomedicines

Self Cite

View full text Add to dashboard Cite

show abstract

“…

…”

mentioning

confidence: 55%

“…We would like to thank Rolf Teschke and Axel Eickhoff for their interest in our work investigating the efficacy and safety of corticosteroid (CS) plus glycyrrhizin (GC) therapy for chronic drug‐or herb‐induced liver injury (DILI/HILI) 1,2 …”

mentioning

confidence: 99%

Editorial: chronic DILI and HILI—corticosteroid plus glycyrrhizin as standard therapy? Authors' reply

Wang

Huang

Wang

et al. 2022

Aliment Pharmacol Ther

View full text Add to dashboard Cite

We would like to thank Rolf Teschke and Axel Eickhoff for their interest in our work investigating the efficacy and safety of corticosteroid (CS) plus glycyrrhizin (GC) therapy for chronic drug-or herb-induced liver injury (DILI/HILI). 1,2 Cessation of the suspected agent(s) is widely recommended and convincingly proved to reverse 80% DILI in the acute phase, 3,4 but this strategy seemed not contributable for patients in our study. It is worth to note that all the participants in two groups of this study have experienced drug cessation at least 6 months prior to therapy, suggesting they had already been patients with chronic DILI and drug cessation alone is not sufficient for DILI intervention. In addition, our study aimed to compare treatment outcome between strategies with and without CS in DILI patients with similar basal conditions, thus the drug cessation is unlikely a confounding factor that would influence our final conclusion. This clinical study is based on a prospectively registered and performed trial (NCT02651350), with randomised and open-labeled design, rather than a retrospective study. We started to recruit

show abstract

Idiosyncratic DILI and RUCAM under One Hat: The Global View

Teschke,

Danan

2023

Livers

Self Cite

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

Editorial: chronic DILI and HILI – corticosteroid plus glycyrrhizin as standard therapy?

Cited by 3 publications

References 13 publications

Treatment of Drug-Induced Liver Injury

Treatment of Drug-Induced Liver Injury

Editorial: chronic DILI and HILI—corticosteroid plus glycyrrhizin as standard therapy? Authors' reply

Idiosyncratic DILI and RUCAM under One Hat: The Global View

Contact Info

Product

Resources

About