Association of CYP2C19 and UGT1A4 polymorphisms with voriconazole-induced liver injury

2020 ◽  
Vol 17 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Yan Song ◽  
Miao-xin Jia ◽  
Guang Yang ◽  
Xin-yuan Feng ◽  
Dong-hong Yin ◽  
...  
Keyword(s):  
Liver Injury ◽  
Gene Polymorphisms ◽  
Rflp Analysis ◽  
Control Group ◽  
Case Group ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Genotype And Allele Frequencies

Aim: This study investigated the association between voriconazole-induced liver injury and gene polymorphisms of CYP2C19 and UGT1A4. Materials & methods: Thirty-eight adult patients who received voriconazole therapy were included in the study. Genotype of CYP2C19 was detected using gene chip hybrid analysis. The UGT1A4 142T>G was genotyped using PCR-RFLP analysis. Results: Ten patients (26.3%) had voriconazole-induced liver injury and were considered as the case group There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19*2 and UGT1A4 142T>G (p > 0.05), however, the GA frequency of CYP2C19 *3 in the drug-induced liver injury case group was higher than that in the control group (p < 0.05). Compared with patients carrying *1/*1 or *1/*2, there was no significant difference in voriconazole trough concentration of the patients with *1/*3 (p > 0.05). Conclusion: There was no significant correlation between voriconazole-induced liver injury and gene polymorphisms of CYP2C19 and UGT1A4.

scholarly journals Relationship between CYP2E1 Gene Polymorphism and Anti-tuberculosis Drug-induced Liver Injury

2018 ◽  
Vol 1 (4) ◽  
pp. 105
Author(s):  
Donglin Zhu ◽  
Yun Xi ◽  
Jieming Dong ◽  
Fanhua Huang ◽  
Changzhi Xu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Gene Polymorphism ◽  
Liver Damage ◽  
Gene Polymorphisms ◽  
Control Group ◽  
Case Group ◽  
Chinese Han ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Cyp2e1 Gene

 Objective: To investigate the relationship between cytochrome P450 E1 (CYP2E1) gene polymorphisms and susceptibility to anti-tuberculosis drug-induced liver damage (ATDLI) in tuberculosis patients in the Chinese Han nationality. Methods: A retrospective analysis was performed on 360 patients with tuberculosis who had liver damage after tuberculosis treatment (case group) and 360 patients with tuberculosis who did not develop liver injury after treatment (control group). MassARRAY were used to detect CYP2E1 gene polymorphisms. Results: In a total of 8 tagged SNP loci selected, the rs8192773 locus failed to pass the test, and therefore, it is not included in subsequent analysis. At the remaining seven SNP sites, the difference in alleles was not statistically significant between the case group and the control group, suggesting that these sites may not be related to liver damage caused by anti-tuberculosis drugs. Three monomer domains were found in the seven tags SNP loci mentioned above. However, it was found that these haplotypes are not closely related to anti-tuberculosis drug-induced liver damage. Conclusion: The CYP2E1 gene polymorphism in the Chinese Han nationality is not related to the occurrence of anti-tuberculosis drug-induced liver injury.

scholarly journals Bicyclol for the treatment of drug-induced liver injury: a propensity score matching analysis using a nationwide inpatient database

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110059
Author(s):  
Yongfeng Wang ◽  
Rongtao Lai ◽  
Peilan Zong ◽  
Qingling Xu ◽  
Jia Shang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Statistical Significance ◽  
Control Group ◽  
Time Interval ◽  
Potential Candidate ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Propensity Score Matching Analysis

ObjectiveTo evaluate the efficacy and safety of bicyclol in patients with drug-induced liver injury (DILI) using a nationwide database.MethodsWe retrospectively analyzed the clinical data of DILI patients in the DILI-R database. Propensity score matching was performed to balance the bicyclol and control groups, and alanine aminotransferase (ALT) recovery was compared between the two groups. Factors associated with ALT recovery and safety were identified.ResultsThe analysis included the data of 25,927 patients. Eighty-seven cases were included in the bicyclol group, with 932 cases in the control group. One-to-one propensity score matching created 86 matched pairs. The ALT normalization rate in the bicyclol group was significantly higher than that in the control group (50.00% vs. 24.42%), and statistical significance was found in the superiority test. After adjustment of baseline ALT levels, baseline total bilirubin levels, sex, age, acute or chronic liver diseases, and suspected drugs in the multivariate logic regression analysis, the major influencing factors for ALT recovery included the time interval between ALT tests (days) and the group factor (bicyclol treatment). There were no differences in the proportion of renal function impairment or blood abnormalities between the two groups.ConclusionsBicyclol is a potential candidate for DILI.

scholarly journals Review: Effect of Red Cabbage Juice (Brassica oleracea var. Capitata f. Rubra) on SGPT Level

2020 ◽  
Vol 3 (1) ◽  
pp. 172-177
Author(s):  
Hesty Wahyuningsih ◽  
Andina Putri Aulia
Keyword(s):  
Liver Injury ◽  
Brassica Oleracea ◽  
Control Group ◽  
Drug Induced ◽  
Red Cabbage ◽  
Drug Induced Liver Injury ◽  
Post Test ◽  
Male Wistar Rats ◽  
Post Hoc ◽  
One Way Anova

Red cabbage (Brassica oleracea var. Capitata f. Rubra) is a vegetable widely used in Indonesian cuisine. Red cabbage is rich in anthocyanins to reduce SGPT levels in drug-induced liver injury (DILI). This study aims to determine the effect of red cabbage juice on SGPT levels in acetaminophen-induced liver injury. In this post-test, only the control group study, male Wistar rats (300g), were randomly divided into 5 groups (K1-K2-K3-K4-K5). Acetaminophen was given to induce liver injury in rats. The rats were treated with the cabbage juice (at the dose of 0.5g/ml or 0.7g/ml or 0.9g/ ml. Data were analyzed using One way ANOVA and LSD post hoc test. Mean SGPT levels for K1, K2, K3, K4, K5 was 58.43 ± 7.18 UI / L, 71.20 ± 9.13 UI/L, 55.73 ± 9.51 UI / L, 72.80 ± 3.47 UI /L, 72.63 ± 3.01 UI /L, respectively. One way ANOVA resulted in p=0.00 (p <0.05). The post hoc LSD test showed significant differences (P <0.05) between all groups except between groups K1-K3, K2-K4, and K2-K5 (p> 0.05). Red cabbage juice can reduce SGPT in acetaminophen-induced liver injury in rats. The most effective dose was 0.5 g/ml.

scholarly journals Is there a correlation between GAD2 gene-243 A>G polymorphism and obesity?

2019 ◽  
Vol 27 (4) ◽  
pp. 413-420
Author(s):  
Camelia Alkhzouz ◽  
Diana Miclea ◽  
Marius Farcas ◽  
Simona Bucerzan ◽  
Georgiana Cabau ◽  
...  
Keyword(s):  
Risk Factor ◽  
Study Groups ◽  
Normal Weight ◽  
Control Group ◽  
Case Group ◽  
Subsequent Increase ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Transcriptional Effect ◽  
And Control

Abstract Introduction: GAD2 gene encodes the glutamate decarboxylase enzyme which catalyses the transformation of glutamate into γ-aminobutyric acid, GABA. It is suggested that some polymorphic alleles of GAD2 gene, such as -243A>G, have an increased transcriptional effect compared with the wild type, which results in an increase of GABA in the hypothalamus with the subsequent increase of the neuropeptide Y, thus exacerbating the hunger centre and the appetite. The aim of this study was to observe an association between the -243A>G polymorphism with obesity, comparatively studying a group of obese patients and a group of patients with normal weight. Patients and method: 127 patients were clinically evaluated in the Genetic and Endocrine Department of Children’s Emergency Clinical Hospital, Cluj. The patients were included in two study groups, case group, with obesity (BMI higher than 97 kg/m2) and control group, with normal weight (BMI less than 97 kg/m2). Genotyping for GAD2-243A>G polymorphism was performed using PCR-RFLP technique, the two groups being compared regarding the genotypes and phenotypes. Results and conclusions: In the obesity group, there is a statistically significant difference in BMI (kg/m2) between the subgroups with different genotypes (p=0.01), the AA genotype being less severely affected than AG and GG genotypes. In the normal weight group there is no association between BMI and different genotypes (AA, AG or GG). Also, there is a greater distribution of GG genotypes and G allele in the obesity group compared with the control group, with an odds ratio which suggest that -243A>G polymorphism is a risk factor in obesity development (GG genotype OR=3.76, G allele OR=1.73, p=0.04). The finding of our study is important in explaining the multifactorial model of obesity, our research demonstrating that the GAD2-243 A> G variant could be a risk factor that added to other obesogenic factors would potentiate their effect.

scholarly journals Prednisolone Therapy Accelerated Recovery of Severe Drug-Induced Liver Injury: A Prospective Randomized Controlled Study

2021 ◽  
Author(s):  
Bing Zhu ◽  
Fangjiao Song ◽  
Honglin Liu ◽  
Yin Sun ◽  
Tianjiao Xu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Injury ◽  
Primary Endpoint ◽  
Controlled Study ◽  
Control Group ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Prednisolone Therapy ◽  
Randomized Controlled ◽  
And Control

Abstract Background Drug-induced liver injury (DILI) is one of the most serious adverse drug reactions and the incidence has been increasing rapidly. Accumulating evidence suggested that the immune activation and systemic inflammatory responses play a significant role in the progression of DILI. Corticosteroids are often used in DILI, but clinical usefulness remain controversial. We therefore conducted a prospective randomized controlled study to investigate whether corticosteroid therapy can accelerate recovery and reduce mortality in severe DILI (SDILI).Methods SDILI patients with total bilirubin (TBIL) ≥171 μmol/L presented to Fifth Medical Center of PLA General Hospital, Beijing from 1/1/2015 to 31/12/2019 were randomized into prednisolone group and control group. The primary endpoints were proportion of subjects with resolution of SDILI defined as decrease in TBIL by at least 35 μmol/L to below 171 μmol/L and overall survival at 6 months. Patients in prednisolone group received prednisolone 60 mg/day therapy for the first 7 days. Patients reaching the primary endpoint or achieved decrease in TBIL by more than 35 umol/L on day 8 would continue on tapering doses of prednisolone, otherwise prednisolone would be discontinued.Results On day 8, 50.7% (34/67) and 26.5% (18/68) of the subjects in the prednisolone group and control group achieved the primary endpoint respectively, p=0.002. However, there was no significant difference in overall survival at 6 months, 95.52% (64/67) vs 91.2% (62/68), p= 0.2. All deaths in both groups occurred in patients who failed to achieve SDILI resolution on day 8.Conclusions Prednisolone therapy may accelerate recovery of SDILI and shorten hospitalization.

scholarly journals Efek pemberian metilprednisolon oral terhadap gambaran histopatologik hati tikus wistar (Rattus norvegicus)

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Muhammad Rifaldi ◽  
Poppy M. Lintong ◽  
Meilany F. Durry
Keyword(s):  
Liver Injury ◽  
Low Dose ◽  
Clinical Manifestations ◽  
Control Group ◽  
High Dose ◽  
Drug Induced ◽  
Treatment Groups ◽  
Drug Induced Liver Injury ◽  
Histopathological Features ◽  
Group B

Abstract: Drug-induced liver injury (DILI) is an adverse drug reaction which vary in its clinical manifestations, ranging from an asymptomatic increase in liver enzymes to fulminant hepatic failure. Several drugs can cause DILI, one of which is corticosteroid. Methylprednisolone (MT) is a kind of corticosteroid drug which is considered to be a safe drug and it is not believed to cause DILI and often used for the treatment of severe hepatitis. However, there are some reports of DILI in patients treated with high-dose MT. The objectives of this study was to determine the effect of oral administration of MT on liver’s histological changes of witar rats. This study was using 15 rats which were divided into 3 groups; 1 negative control group (group A) and 2 treatment groups (group B and group C). Group B was given a low-dose oral MT, 2 mg/day, while group C was given oral high-dose MT, 4 mg/day for 14 consecutive days. The results showed steatohepatitis features in both low-dose and high-dose MT administration groups. Histopathological features of both treatment groups are similar. Qualitatively, high-dose MT group showed worse histopathological features than the low-dose MT group. Conclusion: Administration of MT by 2mg/day and 4mg/day may induced steatohepatitis in wistar rat’s liver.Keywords: methylprednisolone, liver histopathological features Abstrak: Drug-induced liver injury (DILI) atau cedera hati akibat obat merupakan reaksi efek samping obat dengan manifestasi klinis yang beragam, mulai dari peningkatan enzim-enzim hati yang bersifat asimptomatik sampai dengan timbulnya gagal hati fulminan. Banyak obat-obatan yang dapat menyebabkan DILI, salah satunya adalah golongan kortikosteroid. Metilprednisolon (MT) adalah obat golongan kortikosteroid yang dianggap sebagai obat yang aman dan tidak diyakini dapat menyebabkan DILI, bahkan sering digunakan untuk terapi pasien hepatitis berat. Akan tetapi, beberapa klinisi melaporkan kasus DILI pada pasien-pasien yang diterapi dengan MT dosis tinggi. Penelitian ini bertujuan untuk mengetahui efek pemberian MT oral terhadap perubahan histologik hati tikus wistar. Jenis penelitian yang dilakukan adalah eksperimental laboratorik menggunakan 15 ekor tikus yang dibagi dalam 3 kelompok; 1 kelompok kontrol negatif (kelompok A) dan 2 kelompok perlakuan (kelompok B dan kelompok C). Kelompok B diberikan MT oral dosis rendah sebanyak 2 mg/hari sedangkan kelompok C diberikan MT oral dosis tinggi sebanyak 4 mg/hari setiap hari selama 14 hari berturut-turut. Hasil penelitian menunjukkan gambaran yang sama secara mikroskopik pada kedua kelompok perlakuan yaitu terjadinya steatohepatitis. Tetapi secara kualitatif, kelompok tikus yang mendapatkan MT dosis tinggi memberikan gambaran histopatologik yang lebih jelek dibandingkan kelompok yang diberi dosis rendah. Simpulan: Pemberian metilprednisolon dosis 2mg/hari dan dosis 4 mg/hari dapat mencetuskan terjadinya steatohepatitis pada hati tikus wistar. Kata kunci: metilprednisolon, gambaran histopatologik hati

NAT2 Involed in the Susceptibility to Antituberculosis Drug-Induced Liver Injury

2019 ◽  
Vol 2 (3) ◽  
pp. 6
Author(s):  
Donglin Zhu ◽  
Changzhi Xu ◽  
Zhizhi Xie ◽  
Gang Xiao ◽  
Yun Xi
Keyword(s):  
Liver Injury ◽  
Liver Damage ◽  
Control Group ◽  
Case Group ◽  
Antituberculosis Drug ◽  
Drug Induced ◽  
Tuberculosis Patients ◽  
Han Nationality ◽  
Antituberculosis Treatment ◽  
Nat2 Gene

Objective: To investigate whether the N-acetyltransferase 2 (NAT2) gene is involved in the development of susceptibility to antituberculosis drug-induced liver damage (ATDLI) in patients with pulmonary tuberculosis in the Han nationality. Methods: We retrospectively analyzed 300 cases of tuberculosis patients without liver damage (control group) and 221 cases of tuberculosis patients with liver damage after antituberculosis treatment (case group). After antituberculosis treatment, genetic polymorphisms of NAT2 were analyzed in those patients using MassARRAY method. Results: Of the 10 tagged SNPs selected, In the promoter area of NAT2, the frequencies of T allele in rs4646243 and A allele in rs4646246 were signifcantly higher in the patients with ATDLI than controls (0.569 vs. 0.483, p=0.0062 and 0.567 vs 0.487, p=0.0103). The A allele of rs1115784 in the intron area showed a significant association with the development of ATDLI (0.389 vs 0.305, p = 0.0043). The frequencies of the mutated genes T and A in rs1041983 and rs1799930 in the second exon region were significantly higher than those in the control group (0.491 vs 0.360, p<0.00001 and 0.336 vs 0.212, respectively; p<0.00001). Two monomer domains were found in the 10 tag SNP sites, haplotype ht [TGAA] in monomeric domain 1 and haplotype ht [TAG] in monomeric domain 2, both were signifcantly more likely to be detected in the liver injury group than in the control group(p=0.0038, p<0.001, respectively). Two haplotypes were also found on the NAT2 gene: haplotype ht [CGGG] in monomeric domain 1 and ht [CGG] in block 2, and their presence means a lower risk of liver damage. Conclusion: NAT2 genotypes might have signifcant association with the risk of ATDLI in the Chinese Han nationality. By detecting the NAT2 gene and its haplotype, we can screen patients with a higher risk of liver damage before anti-TB treatment and take measures for the protection of patients.

scholarly journals Associations of TGFBR1 and TGFBR2 gene polymorphisms with the risk of hypospadias: a case–control study in a Chinese population

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Xin-Rui Han ◽  
Xin Wen ◽  
Shan Wang ◽  
Xiao-Wu Hong ◽  
Shao-Hua Fan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gene Polymorphisms ◽  
Chinese Population ◽  
Case Control Study ◽  
Case Control ◽  
Control Group ◽  
Case Group ◽  
Abnormal Pregnancy ◽  
Control Study ◽  
Genotype And Allele Frequencies

This case–control study investigated the association of transforming growth factor-β (TGF-β) receptor type I and II (TGFBR1 and TGFBR2) gene polymorphisms with the risk of hypospadias in a Chinese population. One hundred and sixty two patients suffering from hypospadias were enrolled as case group and 165 children who underwent circumcision were recruited as control group. Single nucleotide polymorphisms (SNPs) in TGFBR1 and TGFBR2 genes were selected on the basis of genetic data obtained from HapMap. PCR-restriction fragment length polymorphism (PCR-RFLP) was performed to identify TGFBR1 and TGFBR2 gene polymorphisms and analyze genotype distribution and allele frequency. Logistic regression analysis was conducted to estimate the risk factors for hypospadias. No significant difference was found concerning the genotype and allele frequencies of TGFBR1 rs4743325 polymorphism between the case and control groups. However, genotype and allele frequencies of TGFBR2 rs6785358 in the case group were significantly different in contrast with those in the control group. Patients carrying the G allele of TGFBR2 rs6785358 polymorphism exhibited a higher risk of hypospadias compared with the patients carrying the A allele (P<0.05). The TGFBR2 rs6785358 genotype was found to be significantly related to abnormal pregnancy and preterm birth (both P<0.05). The frequency of TGFBR2 rs6785358 GG genotype exhibited significant differences amongst patients suffering from four different pathological types of hypospadias. Logistic regression analysis revealed that preterm birth, abnormal pregnancy, and TGFBR2 rs6785358 were the independent risk factors for hypospadias. Our study provides evidence that TGFBR2 rs6785358 polymorphism might be associated with the risk of hypospadias.

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