scholarly journals Causality Evaluation of Drug-Induced Liver Injury in Newborns and Children in the Intensive Care Unit Using the Updated Roussel Uclaf Causality Assessment Method

2021 ◽  
Vol 12 ◽  
Author(s):  
Ling Ye ◽  
Zeying Feng ◽  
Longjian Huang ◽  
Chengjun Guo ◽  
Xiong Wu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Hepatic Injury ◽  
Causality Assessment ◽  
Sodium Succinate ◽  
Assessment Method ◽  
Drug Combinations ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Methylprednisolone Sodium Succinate ◽  
Enzyme Metabolism

Purpose: Drug-induced liver injury (DILI) is a common adverse reaction in the clinic; however, there are relatively few reports of DILI in critically ill newborns and children. Making use of the Pediatric Intensive Care database (PIC), this study identifies which drugs are related to DILI in neonates and children in China.Methods: Using the PIC, we screened for patients whose liver was suspected of being injured by drugs during hospitalization. The medicine they used was then assessed by the Roussel Uclaf Causality Assessment Method (RUCAM). At the same time, we also collated drug combinations that may affect CYP (Cytochrome P) enzyme metabolism, which may cause DILI.Results: A total of 13,449 patients were assessed, of whom 77 newborns and 261 children were finally included. The main type of liver injury in neonates was mixed (83.1%), while the hepatic injury types of children were mostly distributed between hepatocellular (59.4%) and cholestatic (28.4%). In terms of the RUCAM assessment, the drugs that were most considered to cause or be associated with hepatic injury in newborns were medium and long chain fat emulsions (17%), sodium glycerophosphate (12%), and meropenem (9%); while omeprazole (11%), methylprednisolone sodium succinate (10%), and meropenem (8%) were the primary culprits of DILI in children. Drug combinations frequently seen in neonates that may affect CYP enzyme metabolism are omeprazole + budesonide (16.9%), dexamethasone + midazolam (10.4%), and midazolam + sildenafil (10.4%). In children, the commonly used drug combinations are fentanyl + midazolam (20.7%), ibuprofen + furosemide (18.4%), and diazepam + omeprazole (15.3%).Conclusions: In this study, medium and long chain fat emulsions and sodium glycerophosphate have been strongly associated with DILI in newborns, while omeprazole and methylprednisolone sodium succinate play an important role in the DILI of children. Also, attention should be paid to the effect on CYP enzymes when using multiple drugs at the same time. In future DILI cases, it is advisable to use the latest RUCAM for prospective study design so that complete case data and high RUCAM scores can be collected.

scholarly journals Drug-Induced Hepatic Injury in Newborns and Children in Intensive Care Unit: A Retrospective Study of China

2021 ◽  
Author(s):  
Ling Ye ◽  
Chengxian Guo ◽  
Zeying Feng ◽  
Longjian Huang ◽  
Chengjun Guo ◽  
...  
Keyword(s):  
Intensive Care ◽  
Liver Injury ◽  
Hepatic Injury ◽  
Sodium Succinate ◽  
Drug Combinations ◽  
Fat Emulsion ◽  
Drug Induced ◽  
Multiple Drugs ◽  
Enzyme Metabolism ◽  
Long Chain

Abstract Purpose Drug-induced liver injury (DILI) is a common adverse reaction in the clinic; however, there are relatively few reports of DILI in critically ill newborns and children. Making use of the Pediatric Intensive Care database (PIC), this study identifies which drugs are related to DILI in neonates and children in China. Methods Using the PIC, we screened for patients whose liver was suspected of being injured by drugs during hospitalization. The medicine they used was then assessed by the Roussel Uclaf Causality Assessment Method (RUCAM). We also collated drug combinations that may affect CYP enzyme metabolism, which may be one of the mechanisms that lead to DILI. Results A total of 13,449 patients were assessed, of whom 77 newborns and 261 children were finally included. The main type of liver injury in neonates was mixed (83.1%), while children’s hepatic injury types were mostly distributed between hepatocellular (59.4%) and cholestatic (28.4%). In terms of the assessment by the RUCAM, in newborns, the drugs that were most considered to cause or associated with hepatic injury comprised medium and long chain fat emulsion (17%), sodium glycerophosphate (12%) and meropenem (9%); while omeprazole (11%), methylprednisolone sodium succinate (10%) and meropenem (8%) are the primary culprit of DILI in children. Drug combinations that may affect CYP enzyme metabolism frequently seen in neonates are omeprazole + budesonide (16.9%), dexamethasone + midazolam (10.4%) and midazolam + sildenafil (10.4%). In children, the commonly used drug combinations are fentanyl + midazolam (20.7%), ibuprofen + furosemide (18.4%) and diazepam + omeprazole (15.3%). Conclusions The drugs that have been found to have hepatotoxicity (meropenem, medium and long chain fat emulsion, ibuprofen.etc.) are also related to DILI in newborns and children. When giving these drugs to newborns and children, physicians need to be more cautious. Also, pay attention to the effect on CYP 450 enzymes when using multiple drugs at the same time.

scholarly journals Circulatory Inflammatory Mediators in the Prediction of Anti-Tuberculous Drug-Induced Liver Injury Using RUCAM for Causality Assessment

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 891
Author(s):  
Cheng-Maw Ho ◽  
Chi-Ling Chen ◽  
Chia-Hao Chang ◽  
Meng-Rui Lee ◽  
Jann-Yuan Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Mediators ◽  
Cox Regression ◽  
Causality Assessment ◽  
Area Under The Curve ◽  
Assessment Method ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Tb Treatment ◽  
Pre Treatment

Background: Anti-tuberculous (TB) medications are common causes of drug-induced liver injury (DILI). Limited data are available on systemic inflammatory mediators as biomarkers for predicting DILI before treatment. We aimed to select predictive markers among potential candidates and to formulate a predictive model of DILI for TB patients. Methods: Adult active TB patients from a prospective cohort were enrolled, and all participants received standard anti-tuberculous treatment. Development of DILI, defined as ≥5× ULN for alanine transaminase or ≥2.6× ULN of total bilirubin with causality assessment (RUCAM, Roussel Uclaf causality assessment method), was regularly monitored. Pre-treatment plasma was assayed for 15 candidates, and a set of risk prediction scores was established using Cox regression and receiver-operating characteristic analyses. Results: A total of 19 (7.9%) in 240 patients developed DILI (including six carriers of hepatitis B virus) following anti-TB treatment. Interleukin (IL)-22 binding protein (BP), interferon gamma-induced protein 1 (IP-10), soluble CD163 (sCD163), IL-6, and CD206 were significant univariable factors associated with DILI development, and the former three were backward selected as multivariable factors, with adjusted hazards of 0.20 (0.07–0.58), 3.71 (1.35–10.21), and 3.28 (1.07–10.06), respectively. A score set composed of IL-22BP, IP-10, and sCD163 had an improved area under the curve of 0.744 (p < 0.001). Conclusions: Pre-treatment IL-22BP was a protective biomarker against DILI development under anti-TB treatment, and a score set by additional risk factors of IP-10 and sCD163 employed an adequate DILI prediction.

scholarly journals Causality assessment in drug-induced liver injury using a structured expert opinion process: Comparison to the Roussel-Uclaf causality assessment method

Hepatology ◽  
2010 ◽  
Vol 51 (6) ◽  
pp. 2117-2126 ◽  
Author(s):  
Don C. Rockey ◽  
Leonard B. Seeff ◽  
James Rochon ◽  
James Freston ◽  
Naga Chalasani ◽  
...  
Keyword(s):  
Liver Injury ◽  
Expert Opinion ◽  
Causality Assessment ◽  
Assessment Method ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Process Comparison

scholarly journals A case report of a drug‐induced liver injury (DILI) caused by multiple antidepressants with causality established by the updated Roussel Uclaf causality assessment method (RUCAM) and in vitro testing

2020 ◽  
Vol 8 (12) ◽  
pp. 3105-3109
Author(s):  
Miguel González‐Muñoz ◽  
Jaime Monserrat Villatoro ◽  
Eva Marín‐Serrano ◽  
Stefan Stewart ◽  
Belén Bardón Rivera ◽  
...  
Keyword(s):  
Case Report ◽  
Liver Injury ◽  
Causality Assessment ◽  
Assessment Method ◽  
In Vitro Testing ◽  
Drug Induced ◽  
Drug Induced Liver Injury

scholarly journals Research Progress of Pharmacogenomics in Drug-Induced Liver Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Qihui Shao ◽  
Xinyu Mao ◽  
Zhixuan Zhou ◽  
Cong Huai ◽  
Zhiling Li
Keyword(s):  
Liver Injury ◽  
Retrospective Studies ◽  
Causality Assessment ◽  
Assessment Method ◽  
Research Progress ◽  
Drug Induced ◽  
Metabolizing Enzymes ◽  
Diagnostic Strategies ◽  
Drug Induced Liver Injury ◽  
Clinical Transformation

Background: Drug-induced liver injury (DILI) is a common and serious adverse drug reaction with insufficient clinical diagnostic strategies and treatment methods. The only clinically well-received method is the Roussel UCLAF Causality Assessment Method scale, which can be applied to both individuals and prospective or retrospective studies. However, in severe cases, patients with DILI still would develop acute liver failure or even death. Pharmacogenomics, a powerful tool to achieve precision medicine, has been used to study the polymorphism of DILI related genes.Summary: We summarized the pathogenesis of DILI and findings on associated genes and variations with DILI, including but not limited to HLA genes, drug metabolizing enzymes, and transporters genes, and pointed out further fields for DILI related pharmacogenomics study to provide references for DILI clinical diagnosis and treatment.Key Messages: At present, most of the studies are mainly limited to CGS and GWAS, and there is still a long way to achieve clinical transformation. DNA methylation could be a new consideration, and ethnic differences and special populations also deserve attention.

Drug-Drug Combinations Can Enhance Toxicity as Shown by Monocyte-Derived Hepatocyte-like Cells From Patients With Idiosyncratic Drug-Induced Liver Injury

2019 ◽  
Vol 171 (2) ◽  
pp. 296-302 ◽  
Author(s):  
Andreas Benesic ◽  
Kowcee Jalal ◽  
Alexander L Gerbes
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Drug Interactions ◽  
Acute Liver Failure ◽  
Causality Assessment ◽  
Drug Combinations ◽  
Positive Interactions ◽  
In Vitro Test ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Abstract Drug-induced liver injury (DILI) is a major cause for acute liver failure and regulatory actions on novel drugs. Individual patient characteristics are the main determinant of idiosyncratic DILI, making idiosyncratic DILI (iDILI) one of the most challenging diagnoses in hepatology. Individual drug-drug interactions might play a role in iDILI. However, the current approaches to iDILI diagnosis are focused on single drugs as causative agents. For the present analysis, 48 patients with acute liver injury who took 2 drugs and who were diagnosed as iDILI were investigated. A novel in vitro test was employed using monocyte-derived hepatocyte-like cells (MH cells) generated from these patients. iDILI diagnosis and causality were evaluated using clinical causality assessment supported by Roussel-Uclaf Causality Assessment Method. In 13 of these 48 patients (27%), combinations of drugs increased toxicity in the MH test when compared with the single drugs. Interestingly, whereas in 24 cases (50%) drug-drug combinations did not enhance toxicity, in 11 cases (23%) only the combinations caused toxicity. The incidence of severe cases fulfilling Hy’s law was higher in patients with positive interactions (57% vs 43%; p = .04), with acute liver failure occurring in 40% versus 8% (p = .01). The most common drug combinations causing increased toxicity were amoxicillin/clavulanate (8 of 9 cases) and diclofenac in combination with steroid hormones (4 of 9 cases). Drug-drug interactions may influence the incidence and/or the severity of idiosyncratic DILI. MH cell testing can identify relevant drug-drug interactions. The data generated by this approach may improve patient safety. Study identifier ClinicalTrials.gov NCT 02353455.

scholarly journals Reliability of the Roussel Uclaf Causality Assessment Method for assessing causality in drug-induced liver injury

Hepatology ◽  
2008 ◽  
Vol 48 (4) ◽  
pp. 1175-1183 ◽  
Author(s):  
James Rochon ◽  
Petr Protiva ◽  
Leonard B. Seeff ◽  
Robert J. Fontana ◽  
Suthat Liangpunsakul ◽  
...  
Keyword(s):  
Liver Injury ◽  
Causality Assessment ◽  
Assessment Method ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Comparing the accuracy of three diagnostic criteria and a refined pathological scoring system in drug-induced liver injury: From suspected to definite

2019 ◽  
Author(s):  
Yiqi Liu ◽  
Ping Li ◽  
Fangfang Wang ◽  
Liang Liu ◽  
Yilian Zhang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Diagnostic Criteria ◽  
Digestive Disease ◽  
Causality Assessment ◽  
Assessment Method ◽  
Operating Characteristics ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Clinical Diagnostic ◽  
Clinical Diagnostic Criteria

Abstract Background Drug-induced liver injury(DILI) is difficult in diagnose, criteria used now are mostly based on history review. We tried to evaluate the value of these criteria and histopathology features in DILI to perform a method diagnosing DILI more definitely.Methods We enrolled 458 consecutive hospitalized DILI patients from 1st January 2012 to 31st December 2018, using Roussel-Uclaf Causality Assessment Method(RUCAM), Maria&Victorino scale (M&V) and Digestive Disease Week-Japan criterion(DDW-J) to perform the evaluation. A refined pathological scale was calculated and combined with those criteria using logistic regression analysis. Area under receiver operating characteristics(AUROC) were used to estimate diagnostic accuracy.Results The AUROC of the three clinical diagnostic criteria were 0.730 (95%CI:0.667-0.793), 0.793(95%CI:0.740-0.847) and 0.764(95%CI:0.702-0.826) respectively. The AUROC of the refined pathological scale combined with the three criteria were 0.843(95%CI:0.747-0.914), 0.907(95%CI:0.822-0.960) and 0.881(95%CI:0.790-0.942) respectively. In hepatocellular type, the AUROCs were 0.894(95%CI:0.787-0.959), 0.960(95%CI:0.857-0.994) and 0.940(95%CI:0.847-0.985); In cholestatic type, the AUROCs were 0.750(95%CI:0.466-0.931), 0.500(95%CI:0.239-0.761) and 0.500(95%CI:0.239-0.761); In mixed type, the AUROCs were 0.786(95%CI: 0.524-0.943), 0.869(95%CI:0.619-0.981) and 0.762(95%CI: 0.498 -0.930).Conclusion Combined with pathological scale can significantly improve the accuracy of clinical diagnostic criteria, no matter in alone or combined condition, M&V might be more accurate in diagnosing DILI from suspected patients.

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