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

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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