scholarly journals Genetic polymorphisms of UGT1A1 and susceptibility to anti-tuberculosis drug-induced liver: A RUCAM-based case–control study

2018 ◽  
Vol 32 ◽  
pp. 205873841881628 ◽  
Author(s):  
Bilin Tao ◽  
Shixian Chen ◽  
Guancheng Lin ◽  
Miaomiao Yang ◽  
Lihuan Lu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Genetic Polymorphisms ◽  
Case Control Study ◽  
Causality Assessment ◽  
Conditional Logistic Regression ◽  
Assessment Method ◽  
Case Control ◽  
Bile Acid Metabolism ◽  
Drug Induced ◽  
Control Study

Uridine 5’-diphospho-glucuronosyl-transferase 1A1 (UGT1A1) plays an important role in the biliary excretion of bilirubin, suggesting genetic polymorphisms of UGT1A1 may have an impact on bile acid metabolism, which may be related to the development of anti-tuberculosis drug-induced liver injury (ATLI). This study explores the associations between genetic polymorphisms of UGT1A1 and ATLI in a Chinese anti-tuberculosis population. A 1:2 matched case–control study was conducted among 290 ATLI cases and 580 controls, of which causality assessment of ATLI cases was based on the updated Roussel Uclaf Causality Assessment Method (RUCAM). Conditional logistic regression was applied to calculate odds ratio (OR) and 95% confidence intervals (CIs), with weight and use of hepatoprotectant as covariates. The Bonferroni correction was used to adjust P values for multiple testing. Compared with those carrying rs6719561 TT genotype, patients with TC genotype had lower risk of ATLI (adjusted OR = 0.723, 95% CI: 0.531–0.985, P = 0.040). The haplotype TAG (rs3755319-rs2003569-rs4148323) could marginally significantly increase the risk of ATLI (adjusted OR = 5.071, 95% CI: 1.007–25.531, P = 0.049), while haplotype TC (rs4148329-rs6719561) could reduce the risk of ATLI (adjusted OR = 0.719, 95% CI: 0.527–0.982, P = 0.038). Patients with polymorphisms at rs4148328 or rs3755319 were at a reduced risk of moderate and severe liver injury under different genetic models. Based on this case–control study, genetic polymorphisms of UGT1A1 may be associated with susceptibility to ATLI in the Chinese anti-tuberculosis population.

scholarly journals Association between genetic polymorphisms of NRF2, KEAP1, MAFF, MAFK and anti-tuberculosis drug-induced liver injury: a nested case-control study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shixian Chen ◽  
Hongqiu Pan ◽  
Yongzhong Chen ◽  
Lihuan Lu ◽  
Xiaomin He ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Genetic Polymorphisms ◽  
Case Control Study ◽  
Case Control ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Tb Treatment ◽  
Nested Case Control ◽  
Control Study

Abstract Reactive metabolites of anti-tuberculosis (anti-TB) drugs can result in excessive reactive oxygen species (ROS), which are responsible for drug-induced liver injury. The nuclear factor erythroid 2-related factor 2 (Nrf2) - antioxidant response elements (ARE) (Nrf2-ARE) signaling pathway plays a crucial role in protecting liver cells from ROS, inducing enzymes such as phase II metabolizing enzymes and antioxidant enzymes. Based on a Chinese anti-TB treatment cohort, a nested case-control study was performed to explore the association between 13 tag single-nucleotide polymorphisms (tagSNPs) in the NRF2, KEAP1, MAFF, MAFK genes in Nrf2-ARE signaling pathway and the risk of anti-TB drug-induced liver injury (ATLI) in 314 cases and 628 controls. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) after adjusting weight and usage of hepatoprotectant. Patients carrying the TC genotype at rs4243387 or haplotype C-C (rs2001350-rs6726395) in NRF2 were at an increased risk of ATLI (adjusted OR = 1.362, 95% CI: 1.017–1.824, P = 0.038; adjusted OR = 2.503, 95% CI: 1.273–4.921, P = 0.008, respectively), whereas patients carrying TC genotype at rs2267373 or haplotype C-G-C (rs2267373-rs4444637-rs4821767) in MAFF were at a reduced risk of ATLI (adjusted OR = 0.712, 95% CI: 0.532–0.953, P = 0.022; adjusted OR = 0.753, 95% CI: 0.587–0.965, P = 0.025, respectively). Subgroup analysis also detected a significant association between multiple tagSNPs (rs4821767 and rs4444637 in MAFF, rs4720833 in MAFK) and specific clinical patterns of liver injury under different genetic models. This study shows that genetic polymorphisms of NRF2, MAFF and MAFK may contribute to the susceptibility to ATLI in the Chinese anti-TB treatment population.

Association Between Drug Exposure and Occurrence of Parkinsonism in Korea: A Population-Based Case-Control Study

2019 ◽  
Vol 53 (11) ◽  
pp. 1102-1110 ◽  
Author(s):  
Siin Kim ◽  
Sang-Myung Cheon ◽  
Hae Sun Suh
Keyword(s):  
Cumulative Dose ◽  
Drug Exposure ◽  
Case Control Study ◽  
Conditional Logistic Regression ◽  
Population Level ◽  
Population Based ◽  
Case Control ◽  
Drug Induced ◽  
Increased Risk ◽  
Control Study

Background: Although drug-induced parkinsonism is reversible in most cases, some patients can suffer from persistent/recurrent symptoms. Therefore, prevention is the most efficient way to manage drug-induced parkinsonism. However, there is a paucity of studies exploring the relationship between parkinsonism and drug exposure. Objective: To examine the association between drug exposure and the risk of parkinsonism using Korean population-based data. Methods: We conducted a matched case-control study using the National Health Insurance Service—National Sample Cohort database. Cases and controls were defined as individuals with and without parkinsonism, respectively, between 2007 and 2013. Cases and controls were matched for sex, age group, income, type of insurance, and Charlson comorbidity index. Drug exposures, including propulsives, antipsychotics, and flunarizine, were identified at 1 year before the first date of parkinsonism and stratified by recency and cumulative dose. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs. Results: We identified 5496 cases and 5496 controls. ORs for current use group of propulsives, antipsychotics, and flunarizine compared with those of the never use group were 2.812 (95% CI = 2.466-3.206), 3.009 (95% CI = 1.667-5.431), and 4.950 (95% CI = 2.711-9.037), respectively. ORs were greater in those more recently exposed and those exposed to higher cumulative doses. Conclusion and Relevance: At the population level, use of propulsives, antipsychotics, and flunarizine had a significant association with the increased risk of parkinsonism, depending on recency and cumulative dose. Drugs associated with parkinsonism should be used with careful monitoring to prevent drug-induced parkinsonism.

scholarly journals Acute and clinically relevant drug-induced liver injury: a population based case-control study

2004 ◽  
Vol 58 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Francisco J. de Abajo ◽  
Dolores Montero ◽  
Mariano Madurga ◽  
Luis A. Garcia Rodriguez
Keyword(s):  
Liver Injury ◽  
Case Control Study ◽  
Population Based ◽  
Case Control ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Control Study

scholarly journals Valproic Acid-Induced Liver Injury: A Case-Control Study from a Prospective Pharmacovigilance Program in a Tertiary Hospital

2021 ◽  
Vol 10 (6) ◽  
pp. 1153
Author(s):  
Enrique S. Meseguer ◽  
Mikel U. Elizalde ◽  
Alberto M. Borobia ◽  
Elena Ramírez
Keyword(s):  
Valproic Acid ◽  
Liver Injury ◽  
Case Control Study ◽  
Monitoring Program ◽  
Case Control ◽  
University Hospital ◽  
Control Groups ◽  
Retrospective Case ◽  
Drug Induced ◽  
Control Study

Introduction: Valproic acid (VPA) is an antiepileptic drug extensively used for treating partial and generalised seizures, acute mania and as prophylaxis for bipolar disorder. Drug-induced liver injury (DILI) persists as a significant issue related to fatal outcomes by VPA. The aim of this study was to increase our knowledge about this condition and to better identify patients affected. Methods: We conducted an observational retrospective case-control study that identified cases of DILI by VPA from the Pharmacovigilance Programme from our Laboratory Signals at La Paz University Hospital from January 2007 to December 2019. From the Therapeutic VPA Monitoring program, two control groups were assigned, VPA-tolerant patients and the other with patients who developed mild VPA-related liver injury but who did not meet the DILI criteria, matched for date, age and sex. Results: A total of 60 patients were included in the study: 15 cases of DILI, 30 VPA-tolerant controls and 15 controls with mild liver injury. Mean age for the cases was 45.7 years, 4 (26.7%) were women and 5 (33.34%) were children under 18 years, of them 3 (20%) were fatal. Polytherapy with other antiepileptic drugs (p = 0.047) and alcohol consumption (p < 0.001) were associated with a greater risk of developing DILI by VPA. A diagnosis of epileptic seizure was more frequently related to DILI when compared with the VPA-tolerant controls (p < 0.001). The cases developed hepatocellular liver injury (p < 0.001), while the mild hepatic damage controls had a higher rate of cholestatic liver injury (p < 0.001). The laboratory lactate dehydrogenase values were statistically higher (even at baseline) in patients with DILI than in both control groups (p = 0.033 and p = 0.039). Conclusions: VPA hepatotoxicity remains a considerable problem. This study offers interesting findings for characterising VPA-induced liver injury and at-risk patients.

scholarly journals Valproic Acid-Induced Liver Injury: A Case-Control Study from a Prospective Pharmacovigilance Program in a Tertiary Hospital

2021 ◽  
Author(s):  
Enrique Seco Meseguer ◽  
Mikel Urroz Elizalde ◽  
Alberto M. Borobia ◽  
Elena Ramírez
Keyword(s):  
Valproic Acid ◽  
Liver Injury ◽  
Case Control Study ◽  
Tertiary Hospital ◽  
Case Control ◽  
University Hospital ◽  
Control Groups ◽  
Retrospective Case ◽  
Drug Induced ◽  
Control Study

Introduction: Valproic acid (VPA) is an antiepileptic drug extensively used for treating partial and generalised seizures, acute mania and as prophylaxis for bipolar disorder. Drug-induced liver injury (DILI) persists as a significant issue related to fatal outcomes by VPA. The aim of this study was to increase our knowledge about this condition and to better identify patients affected. Methods: We conducted an observational retrospective case-control study that identified cases of DILI by VPA from the Pharmacovigilance Programme from our Laboratory Signals at La Paz University Hospital from January 2007 to December 2019. From the Therapeutic VPA Monitoring Programme, two control groups were assigned, VPA-tolerant patients and the other with patients who developed mild VPA-related hepatitis but who did not meet the DILI criteria, matched for date, age and sex. Results: A total of 60 patients were included in the study: 15 cases of DILI, 30 VPA-tolerant controls and 15 controls with mild hepatitis. Mean age for the cases was 45.7 years, 4(26.7%) were women and 5(33.34%) were children under 18 years, of them 3(20%) were fatal. Polytherapy with other antiepileptic drugs (p=0.047) and alcohol consumption (p&lt;0.001) were associated with a greater risk of developing DILI by VPA. A diagnosis of epileptic seizure was more frequently related to DILI when compared with the VPA-tolerant controls (p&lt;0.001). The cases developed hepatocellular hepatitis (p&lt;0.001), while the mild hepatitis controls had a higher rate of cholestatic hepatitis (p&lt;0.001). The laboratory lactate dehydrogenase values were statistically higher (even at baseline) in patients with DILI than in both control groups (p= 0.033 and p=0.039). Conclusions: VPA hepatotoxicity remains a considerable problem. This study offers interesting findings for characterising VPA-induced liver injury and at-risk patients.

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