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 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 CYP2E1, GSTM1, and GSTT1 genetic polymorphisms and their associations with susceptibility to antituberculosis drug-induced liver injury in Thai tuberculosis patients

Heliyon ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. e06852
Author(s):  
Noppadol Chanhom ◽  
Sukanya Wattanapokayakit ◽  
Nusara Satproedprai ◽  
Supharat Suvichapanich ◽  
Surakameth Mahasirimongkol ◽  
...  
Keyword(s):  
Liver Injury ◽  
Genetic Polymorphisms ◽  
Antituberculosis Drug ◽  
Drug Induced ◽  
Tuberculosis Patients ◽  
Drug Induced Liver Injury

scholarly journals Association of Genetic Polymorphism of GSTM1 and GSTT1 with the Susceptibility to Antituberculosis Drug-induced Hepatotoxicity in Chinese Population

2018 ◽  
Vol 1 (3) ◽  
pp. 80
Author(s):  
Gang Xiao
Keyword(s):  
Liver Toxicity ◽  
Control Group ◽  
Case Group ◽  
Antituberculosis Drug ◽  
Drug Induced ◽  
Antituberculous Treatment ◽  
Gstm1 Gene ◽  
Gstt1 Gene ◽  
The Difference ◽  
And Control

Objective To investigate the relationship between the polymorphism of glutathione S transferase M1, T1(GSTM1, GSTT1) gene and the susceptibility to antituberculosis drug induced hepatotoxicity (ATDH) in patients with tuberculosis. Methods GSTM1 and GSTT1 gene polymorphisms in patients with or without liver toxicity after antituberculous treatment were analyzed using multiple PCR method. Results In ATDH group and control group, the proportion of GSTM1 gene deletion was 58.0% and 50.7%respectively, and the difference was not statistically signifcant (OR=1.322, 95%CI=0.921~1.878), the frequencies of GSTT1 deletion were 46.3% and 49.3%, respectively, and there was no signifcant difference between them. There was no signifcant difference in frequency of GSTM1 and GSTT1 variation between case group and control group (P> 0.05), and no synergistic effect of those two gene polymorphism were detected in the occurrence of antituberculosis drug-induced hepatotoxicity. Conclusion The polymorphisms of GSTM1 and GSTT1 genes may not be associated with the risk of ATDH.

scholarly journals The Variant at TGFBRAP1 but Not TGFBR2 Is Associated with Antituberculosis Drug-Induced Liver Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Jingwei Zhang ◽  
Zhenzhen Zhao ◽  
Hao Bai ◽  
Lin Jiao ◽  
Qian Wu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Genetic Model ◽  
Joint Effect ◽  
Dependent Manner ◽  
Antituberculosis Drug ◽  
Drug Induced ◽  
Effect Analysis ◽  
Tuberculosis Patients ◽  
Drug Induced Liver Injury ◽  
Increased Risk

Background. TGFBRAP1 and TGFBR2 play important roles in the TGF-β/smad signalling pathway and may disturb liver homeostasis by regulating liver injury and renewal. However, little is known about the association between their genetic polymorphisms and antituberculosis drug-induced liver injury (ATDILI), so we explored the association between their variants and the susceptibility to ATDILI. Materials and Methods. A total of 746 tuberculosis patients were prospectively enrolled, and fifteen selected SNPs were genotyped. The allele, genotype, and genetic model frequencies of the variants were compared between patients with or without ATDILI, as well as the joint effect analysis of SNP-SNP interactions. The odds ratio (OR) with the corresponding 95% confidence interval (CI) was calculated. Results. The A variant at rs17687727 was significantly associated with an increased risk for ATDILI (OR 1.55; 95% CI: 1.08–2.22; p=0.016), which is consistent with the results in the additive and dominant models. Other allele, genotype, and genetic model frequencies were similar in the two groups for the other fourteen SNPs (all p>0.05). Conclusion. Our study first implied that the A variant of rs17687727 in TGFBRAP1 influenced the susceptibility to ATDILI in first-line antituberculosis combination treatment in the Han Chinese population in a dependent manner.

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 Faktor Risiko Terjadinya Hepatotoksisitas Imbas Obat Antituberkulosis pada Pasien HIV/AIDS

2017 ◽  
Vol 4 (1) ◽  
pp. 23
Author(s):  
Lies Luthariana ◽  
Teguh H. Karjadi ◽  
Irsan Hasan ◽  
C. Martin Rumende
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Hepatitis C ◽  
Hepatitis B ◽  
Control Group ◽  
Case Group ◽  
Antituberculosis Drug ◽  
Aids Patients ◽  
Drug Induced ◽  
Hiv Aids

Pendahuluan. Hepatotoksisitas imbas antituberkulosis (OAT) banyak didapatkan pada pasien HIV/AIDS. Beberapa faktor risiko terjadinya hepatotoksisitas imbas obat seperti alkoholisme, infeksi hepatitis B maupun C, abnormalitas transaminase, status gizi kurang, penggunaan beberapa obat hepatotoksik secara bersamaan, banyak didapatkan pada pasien-pasien tersebut. Dengan karakteristik pasien HIV/AIDS yang berbeda dengan di negara lain maka diperlukan penelitian tersendiri tentang risiko terjadinya hepatotoksisitas imbas OAT pada pasien tersebut di Indonesia. Penelitian ini dilakukan untuk mengetahui faktor risiko terjadinya hepatotoksisitas imbas OAT pada pasien HIV.Metode. Desain penelitian ini adalah studi retrospektif kasus-kontrol dengan matching usia, jenis kelamin, regimen OAT dan konsumsi alkohol. Faktor risiko yang diteliti adalah koinfeksi hepatitis C, hepatitis B, konsumsi obat hepatotoksik lainnya, dan abnormalitas nilai awal SGPT dan atau billirubin total.Hasil. Pada penelitian ini diperoleh 33 kasus dan 33 kontrol. Proporsi subjek dengan koinfeksi hepatitis C sebesar 82% pada kasus dan 76% pada kontrol, sedangkan proporsi subjek dengan koinfeksi hepatitis B sebesar 18% pada kasus dan 6% pada kontrol. Subjek dengan nilai SGPT awal meningkat didapatkan pada kelompok kasus sebesar 51,5% dan pada kontrol sebesar 12%. Sementara itu, proporsi subjek yang menggunakan obat hepatotoksik lainnya sebesar 54,5% pada kasus dan 42,4% pada kontrol. Pada analisis bivariat, hanya nilai SGPT awal yang meningkat yang berhubungan dengan kejadian hepatotoksisitas imbas OAT (OR=7,5; IK95% 1,72-32,80; p < 0,05).Simpulan. Nilai SGPT awal yang meningkat dapat meningkatkan risiko terjadinya hepatotoksisitas imbas OAT pada pasien HIV/AIDS sebesar 7,5 kali. Tidak didapatkan hubungan koinfeksi hepatitis C, hepatitis B dan penggunaan obat hepatotoksik lainnya dengan kejadian hepatotoksisitas imbas OAT pada pasien HIV/AIDS.Kata Kunci: hepatotoksisitas imbas OAT, HIV/AIDS, tuberkulosis Risk Factors of Antituberculosis Induced-Hepatotoxicity among HIV/AIDS PatientsIntroduction. Antituberculosis (ATT) induced hepatotoxicity is commonly found among HIV/AIDS patients. Several risk factor related to drug-induced hepatotoxicity such as alcoholism, hepatitis B or hepatitis C infection, abnormal baseline aminotransferase/bilirubin, poor nutritional status and concomitant hepatotoxic drugs consumption, are usually found in these patients. This study was conducted to evaluate risk factor of ATT-induced hepatotoxicity in HIV/AIDS patients. Methods. This is a case control retrospective study with matching of age, sex, antituberculosis regimen, and alcohol consumption. Risk factors evaluated are hepatitis C and hepatitis B coinfection, concomitant hepatotoxic drugs consumption, abnormal baseline aminotransferase and or bilirubin.Results. We collected data of 33 cases and 33 controls We found 82% subjects in case group and 76% subjects in control group have hepatitis C coinfection; 18% subjects in case group and 6% subjects in control group have hepatitis B coinfection. Fifty four point five percent (54.5%) subjects in case group and 42.4% subjects in control group consume other hepatotoxic drugs. Elevated baseline ALT level was found in 51.5% subjects in case group and 12% subject in control group. Bivariate analysis showed that the risk of hepatotoxicity was higher in patients with elevated baseline ALT level (OR=7.5; 95% CI 1,7232,80; p < 0,05).Conclusions. Elevated baseline ALT level will increase antituberculosis drug induce hepatotoxicity risk up to 7.5 times. There were no association between hepatitis C, hepatitis B, concomitant hepatotoxic drugs consumption and antituberculosis drug-induced hepatotoxicity in HIV/AIDS patients.

scholarly journals Association of UGT2B7 polymorphisms with risk of induced liver injury by anti-tuberculosis drugs in Chinese Han

2017 ◽  
Vol 30 (4) ◽  
pp. 434-438 ◽  
Author(s):  
Guo Chen ◽  
Shou-Quan Wu ◽  
Mei Feng ◽  
Yu Wang ◽  
Jing-Can Wu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Disorder ◽  
Control Group ◽  
Case Group ◽  
Uridine Diphosphate ◽  
Chinese Han ◽  
Drug Induced ◽  
Tag Snps ◽  
Genotype Frequencies ◽  
Lost To Follow Up

Anti-tuberculosis drug-induced liver injury (ATLI) is common during the treatment of tuberculosis (TB). As an important enzyme in the metabolism of many drugs, UGT2B7 (uridine diphosphate glucuronyl transferase 2B7) was associated with drug-induced liver disorder. This study investigated the association between the polymorphisms of UGT2B7 and ATLI in Chinese Han. Totally, 280 newly diagnosed TB patients had been followed up for 3 months after the prescription of anti-TB therapy. Tag-single-nucleotide polymorphism (tag-SNPs) (rs10028494 and rs7668282) were genotyped with the MassARRAY platform. The associations between tag-SNPs and ATLI risk were analyzed by logistic regression analysis adjusting for confounding factors. In this prospective study, 33 patients were lost to follow-up, and 24 patients were diagnosed with ATLI and considered as the case group. The remaining 223 subjects without ATLI were considered as the control group. No significant association was observed in allele and genotype frequencies of UGT2B7 between the two groups. This study is the first attempt to investigate the association of genetic polymorphisms of UGT2B7 with ATLI in Chinese Han. There is no significant association between UGT2B7 polymorphisms and ATLI in Chinese Han.

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.

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