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.

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 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.

scholarly journals Drug Induced Liver Injury Attributed to a Curcumin Supplement

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Zaid Imam ◽  
Majd Khasawneh ◽  
Diana Jomaa ◽  
Hira Iftikhar ◽  
Ziad Sayedahmad
Keyword(s):  
Liver Injury ◽  
Causality Assessment ◽  
Assessment Method ◽  
Careful Evaluation ◽  
Recurrence Rates ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Upper Limit ◽  
Extensive Evaluation ◽  
Related Drug

More severe reactions, higher acute liver failure rates, and higher recurrence rates on re-challenge occur with supplement-related Drug Induced Liver Injury (DILI) (Medina-Caliz et al., 2018). We report a case of curcumin-induced hepatocellular DILI in a 78-year old female admitted with jaundice, with a one-month latency. Extensive evaluation for alternative etiologies of hepatotoxicity was unremarkable. The Roussel Uclaf Causality Assessment Method (RUCAM) score of 6 for the supplement indicated a probable association (score >8: highly probable association). Peak levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were >20 times upper limit of normal. A 48% decrease in AST and ALT levels was observed 7 days after discontinuation of the supplement, and resolution of transaminitis was observed in 42 days. No re-challenge was performed. In conclusion, this case emphasizes the importance of recognizing curcumin supplements as DILI triggers. Furthermore, it reiterates the need for careful evaluation of herbal and dietary supplements (HDS) consumed by patients to identify potential DILI culprits, and to ultimately prevent DILI reactions with significant morbidity and mortality.

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