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 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 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.

Marked Increase of Gamma-Glutamyltransferase as an Indicator of Drug-Induced Liver Injury in Patients without Conventional Diagnostic Criteria of Acute Liver Injury

2021 ◽  
pp. 1-6
Author(s):  
Sabine Weber ◽  
Julian Allgeier ◽  
Gerald Denk ◽  
Alexander L. Gerbes
Keyword(s):  
Liver Injury ◽  
Case Series ◽  
Assessment Method ◽  
Close Monitoring ◽  
In Vitro Test ◽  
Drug Induced ◽  
Gamma Glutamyltransferase ◽  
Drug Induced Liver Injury ◽  
Full Remission

<b><i>Introduction:</i></b> Clinically significant drug-induced liver injury (DILI) is defined by elevations of alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), alkaline phosphatase (ALP) ≥2 × ULN, or ALT ≥3 × ULN and total bilirubin TBIL &#x3e;2 × ULN. However, DILI might also occur in patients who do not reach those thresholds and still may benefit from discontinuation of medication. <b><i>Methods:</i></b> Fifteen patients recruited for our prospective study on potentially hepatotoxic drugs were included. DILI diagnosis was based on RUCAM (Roussel Uclaf Causality Assessment Method) score and expert opinion and was supported by an in vitro test using monocyte-derived hepatocyte-like (MH) cells. <b><i>Results:</i></b> Median RUCAM score was 6 (range 4–8), indicating that DILI was possible or probable in all cases. The predominant types of liver injury were mixed (60%) and cholestatic (40%). While no elevation above 2 × ULN of ALP and TBIL was observed, gamma-glutamyltransferase (GGT) above 2 × ULN was identified in 8 of the patients. Six of the 15 patients did not achieve full remission and showed persistent elevation of GGT, which was significantly associated with peak GGT elevation above 2 × ULN (<i>p</i> = 0.005). <b><i>Conclusion:</i></b> Here we present a case series of patients with liver enzyme elevation below the conventional thresholds who developed DILI with a predominant GGT elevation leading to drug withdrawal and/or chronic elevation of liver parameters, in particular of GGT. Thus, we propose that DILI should be considered in particular in cases with marked increase of GGT even if conventional DILI threshold levels are not reached, resulting in discontinuation of the causative drug and/or close monitoring of the patients.

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

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.

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